03.18.14
A study published recently in JAMA Internal Medicine failed to detect a benefit of omega-3 fatty acids for cardiovascular disease while another published in Annals of Internal Medicine challenged common guidelines about dietary fats.
The first, the Cardiovascular Outcome Study (COS) was an ancillary study of the Age-Related Eye Disease Study 2 (AREDS2), a factorial-designed randomized clinical trial of 4,203 participants recruited from 82 U.S. academic and community ophthalmology clinics, who were followed up for a median of 4.8 years. Individuals were eligible to participate if they were between the ages of 50 and 85 years, had intermediate or advanced age-related macular degeneration in 1 eye, and were willing to be randomized. Participants with stable, existing CVD (>12 months since initial event) were eligible to participate. Participants, staff and outcome assessors were masked to intervention.
Subjects received daily supplementation with long-chain omega-3 polyunsaturated fatty acids (350 mg DHA + 650 mg EPA), macular xanthophylls (10 mg lutein + 2 mg zeaxanthin), combination of the two, or matching placebos. These treatments were added to background therapy of the AREDS vitamin and mineral formulation for macular degeneration.
A total of 602 cardiovascular events were adjudicated, and 459 were found to meet one of the study definitions for a CVD outcome. In intention-to-treat analysis, no reduction in the risk of CVD or secondary CVD outcomes was seen for the DHA + EPA or lutein + zeaxanthin groups, according to researchers.
The Global Organization for EPA and DHA Omega-3 (GOED) noted in an assessment that the study was under-powered to find an effect in a population that included both healthy individuals and those being treated for CVD. “The AREDS2 was powered to detect a change in macular degeneration, not cardiovascular events in a population that includes both healthy subjects and CVD patients. In addition, the primary endpoint combined all CVD events into a single endpoint to be studied, which makes it more difficult to detect an effect compared to looking at individual CVD outcomes like cardiac death. As a result, this study was grossly under-powered, so it should come as no surprise that no overall CVD risk reduction was demonstrated. In this case, there was a failure to detect an effect, not a lack of effect(s).”
GOED also noted, “The study still showed a significant benefit for people without a history of hypertension and trended towards a benefit in people without CVD. Recent meta-analyses by Kwak et al, and Rizos et al, have looked at the broader totality of evidence in similar mixed prevention scenarios and found a 9% reduction in cardiac death.”
Duffy MacKay, ND, senior vice president, scientific and regulatory affairs, Council for Responsible Nutrition (CRN), said omega-3 fatty acids found in fish and dietary supplements promote better health by helping to reduce the long-term risks of cardiovascular disease. “This study demonstrates exactly these positive results with certain populations in the study. It’s unfortunate that the race to sensationalize the less beneficial outcomes for other subgroups may overshadow the real benefits of long-term usage of omega-3s. For example, the researchers found a significant protective effect against cardiovascular disease for those taking omega-3 supplements who had no previous history of hypertension.”
Researchers acknowledged limitations of their study, according to CRN, saying, “The AREDS2 participants were older, and many had existing CVD or elevated risk for CVD.” They also advised, “We cannot exclude a beneficial effect from starting supplementation earlier in life.”
The study published in Annals of Internal Medicine, aimed to summarize evidence about associations between fatty acids and coronary disease, assessing prospective, observational studies and randomized, controlled trials from MEDLINE, Science Citation Index and Cochrane Central Register of Controlled Trials through July 2013.
There were 32 observational studies (530,525 participants) of fatty acids from dietary intake; 17 observational studies (25,721 participants) of fatty acid biomarkers; and 27 randomized, controlled trials (103,052 participants) of fatty acid supplementation.
After assessment, researchers concluded current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.
According to GOED’s evaluation of this study, this report doesn’t attack the premise that individual fatty acids may be good or bad. “Instead it is targeting blanket recommendations that people increase intake of all omega-3s, all omega-6s, and decrease all saturated fats.”
“Similar to the study reported in JAMA Internal Medicine, this study mixed primary and secondary prevention and did not tease out individual coronary events. Despite this issue, the authors reported a 25% decreased risk of coronary outcomes associated with circulating EPA+DHA. In addition, dietary intakes of long-chain omega-3s, and also long-chain omega-3 supplementation, demonstrated a protective effect that, while large enough to be relevant for public health recommendations, just missed reaching statistical significance. Together, these results provide compelling evidence to increase EPA and DHA consumption from either dietary sources of EPA and DHA like fatty fish or supplementation as part of a healthy diet and lifestyle.”
GOED also noted the following key findings:
• Supplementation with 1-2 grams/day of long-chain omega-3s (e.g. EPA+DHA) showed a strong trend (p=0.056) towards decreasing the risk of coronary outcomes.
• The need for long-term studies is supported by a 14% decreased risk of coronary outcomes in dietary intake studies with follow-ups greater than or equal to 10 years.
• For long-chain omega-3 intake (e.g. EPA+DHA), the addition of sudden cardiac death to the mix of endpoints yielded a beneficial 39% risk reduction.
Dr. MacKay noted there are thousands of studies and decades of recommendations supporting the heart health benefits associated with diets high in polyunsaturated fats, low in saturated fats and avoidance of trans fats.
“This systematic review and meta-analysis raises an interesting viewpoint, but an unfortunate, and potentially irresponsible one, for consumers who will once again be subject to nutritional guidance whiplash. We were pleased to see the researchers recognized that studying nutrition has different nuances than studying drugs, and therefore included the wide breadth of research, including biomarker studies, observational studies and randomized controlled trials in their systematic review and meta-analysis. Unfortunately, their conclusions, if taken to heart, leave consumers to rely on genetics and fate to avoid coronary heart disease, an unacceptable situation given the fact that the scientific literature contains so many studies that point to benefit for omega-3 fatty acids.”
The first, the Cardiovascular Outcome Study (COS) was an ancillary study of the Age-Related Eye Disease Study 2 (AREDS2), a factorial-designed randomized clinical trial of 4,203 participants recruited from 82 U.S. academic and community ophthalmology clinics, who were followed up for a median of 4.8 years. Individuals were eligible to participate if they were between the ages of 50 and 85 years, had intermediate or advanced age-related macular degeneration in 1 eye, and were willing to be randomized. Participants with stable, existing CVD (>12 months since initial event) were eligible to participate. Participants, staff and outcome assessors were masked to intervention.
Subjects received daily supplementation with long-chain omega-3 polyunsaturated fatty acids (350 mg DHA + 650 mg EPA), macular xanthophylls (10 mg lutein + 2 mg zeaxanthin), combination of the two, or matching placebos. These treatments were added to background therapy of the AREDS vitamin and mineral formulation for macular degeneration.
A total of 602 cardiovascular events were adjudicated, and 459 were found to meet one of the study definitions for a CVD outcome. In intention-to-treat analysis, no reduction in the risk of CVD or secondary CVD outcomes was seen for the DHA + EPA or lutein + zeaxanthin groups, according to researchers.
The Global Organization for EPA and DHA Omega-3 (GOED) noted in an assessment that the study was under-powered to find an effect in a population that included both healthy individuals and those being treated for CVD. “The AREDS2 was powered to detect a change in macular degeneration, not cardiovascular events in a population that includes both healthy subjects and CVD patients. In addition, the primary endpoint combined all CVD events into a single endpoint to be studied, which makes it more difficult to detect an effect compared to looking at individual CVD outcomes like cardiac death. As a result, this study was grossly under-powered, so it should come as no surprise that no overall CVD risk reduction was demonstrated. In this case, there was a failure to detect an effect, not a lack of effect(s).”
GOED also noted, “The study still showed a significant benefit for people without a history of hypertension and trended towards a benefit in people without CVD. Recent meta-analyses by Kwak et al, and Rizos et al, have looked at the broader totality of evidence in similar mixed prevention scenarios and found a 9% reduction in cardiac death.”
Duffy MacKay, ND, senior vice president, scientific and regulatory affairs, Council for Responsible Nutrition (CRN), said omega-3 fatty acids found in fish and dietary supplements promote better health by helping to reduce the long-term risks of cardiovascular disease. “This study demonstrates exactly these positive results with certain populations in the study. It’s unfortunate that the race to sensationalize the less beneficial outcomes for other subgroups may overshadow the real benefits of long-term usage of omega-3s. For example, the researchers found a significant protective effect against cardiovascular disease for those taking omega-3 supplements who had no previous history of hypertension.”
Researchers acknowledged limitations of their study, according to CRN, saying, “The AREDS2 participants were older, and many had existing CVD or elevated risk for CVD.” They also advised, “We cannot exclude a beneficial effect from starting supplementation earlier in life.”
The study published in Annals of Internal Medicine, aimed to summarize evidence about associations between fatty acids and coronary disease, assessing prospective, observational studies and randomized, controlled trials from MEDLINE, Science Citation Index and Cochrane Central Register of Controlled Trials through July 2013.
There were 32 observational studies (530,525 participants) of fatty acids from dietary intake; 17 observational studies (25,721 participants) of fatty acid biomarkers; and 27 randomized, controlled trials (103,052 participants) of fatty acid supplementation.
After assessment, researchers concluded current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.
According to GOED’s evaluation of this study, this report doesn’t attack the premise that individual fatty acids may be good or bad. “Instead it is targeting blanket recommendations that people increase intake of all omega-3s, all omega-6s, and decrease all saturated fats.”
“Similar to the study reported in JAMA Internal Medicine, this study mixed primary and secondary prevention and did not tease out individual coronary events. Despite this issue, the authors reported a 25% decreased risk of coronary outcomes associated with circulating EPA+DHA. In addition, dietary intakes of long-chain omega-3s, and also long-chain omega-3 supplementation, demonstrated a protective effect that, while large enough to be relevant for public health recommendations, just missed reaching statistical significance. Together, these results provide compelling evidence to increase EPA and DHA consumption from either dietary sources of EPA and DHA like fatty fish or supplementation as part of a healthy diet and lifestyle.”
GOED also noted the following key findings:
• Supplementation with 1-2 grams/day of long-chain omega-3s (e.g. EPA+DHA) showed a strong trend (p=0.056) towards decreasing the risk of coronary outcomes.
• The need for long-term studies is supported by a 14% decreased risk of coronary outcomes in dietary intake studies with follow-ups greater than or equal to 10 years.
• For long-chain omega-3 intake (e.g. EPA+DHA), the addition of sudden cardiac death to the mix of endpoints yielded a beneficial 39% risk reduction.
Dr. MacKay noted there are thousands of studies and decades of recommendations supporting the heart health benefits associated with diets high in polyunsaturated fats, low in saturated fats and avoidance of trans fats.
“This systematic review and meta-analysis raises an interesting viewpoint, but an unfortunate, and potentially irresponsible one, for consumers who will once again be subject to nutritional guidance whiplash. We were pleased to see the researchers recognized that studying nutrition has different nuances than studying drugs, and therefore included the wide breadth of research, including biomarker studies, observational studies and randomized controlled trials in their systematic review and meta-analysis. Unfortunately, their conclusions, if taken to heart, leave consumers to rely on genetics and fate to avoid coronary heart disease, an unacceptable situation given the fact that the scientific literature contains so many studies that point to benefit for omega-3 fatty acids.”
