Diet and Atrial Fibrillation: Does alpha Linolenic Acid, A Plant Derived Essential Fatty Acid, Have An Impact?
Diet and Atrial Fibrillation: Does alpha Linolenic Acid, A Plant Derived Essential Fatty Acid, Have An Impact?
Year: 2013
Authors: Kastner, D.W. Van Wagoner, D.R.
Publication Name: J Am Heart Assoc.
Publication Details: doi: 10.1161/JAHA.112.000030
Abstract:
This letter is a comment in response to “Associations of plasma phospholipid and dietary alpha linolenic acid with incident atrial fibrillation in older adults: the Cardiovascular Health Study. [J Am Heart Assoc. 2013]”. A summary of the key points is found here.
Many studies in the past 50 years have shown that dietary lipids can modulate the progression of coronary artery disease, heart failure, and cardiac arrhythmogenesis. While fish are the most concentrated natural source of EPA and DHA, alpha linolenic acid (ALA) is the most abundant plant based n3 PUFA. Can dietary consumption of ALA, an abundant, sustainable and inexpensive n3 PUFA, lower the risk of AF in the same manner that consumption of fish and DHA appear to do? Fretts and colleagues directly address this important question. They use an epidemiologic approach to assess the relationship between plasma ALA levels, dietary ALA consumption, and AF risk. In their study of 2899 subjects (65 years or older at study entry), there were 707 cases of incident AF during a 15 to 16 year (nearly 30 000 person years) follow up. No relationship was detected between plasma ALA and incident AF after correcting for age, sex, and a variety of clinical and demographic factors. Strengths of the study include the size and age of the population, and the relatively large fraction of incident AF. Their results are consistent with an epidemiologic analysis suggesting that from age 40, there is approximately a 25 per cent lifetime risk of developing AF for both men and women. Technical weaknesses of the study include the measurement of plasma ALA levels at only a single time point, and the reliance on food questionnaires to assess the level of dietary ALA consumption. What are the implications of this study? The authors have concluded that neither ALA consumption nor plasma ALA levels are associated with AF risk. On the basis of their data, this seems to be a reasonable analysis and summary for their study. However, we argue that the conclusion that ALA consumption is not related to AF risk is premature as a general statement. It is interesting to note that a similar epidemiologic study has recently reported a beneficial impact of dietary ALA with respect to risk of heart failure. AF and heart failure are frequently comorbid conditions. It seems likely that diets that substantially increase consumption of ALA while decreasing the intake of n6 PUFA will have a beneficial impact on cardiovascular morbidity and mortality. However, optimal testing of this hypothesis would require careful longitudinal analysis of a cohort of patients with serial assessment of plasma PUFA levels, cardiovascular biomarkers, cardiac function, and electrophysiology. Most enzymes that metabolize PUFAs do not distinguish between n3 and n6 isoforms. The rate of conversion is dependent on the relative abundance of each substrate. If the n 6 PUFAs are abundant, the conversion of short chain to long chain n3 PUFAs will be inhibited. Short chain PUFA such as ALA and linolenic acid (LA, n 6) are converted to long chain PUFA (eg., arachidonic acid [AA], EPA, DHA) by elongase and desaturase enzymes. The rate of conversion of ALA to EPA and DHA thus depends on the ratio of n3 to n 6 PUFA in the diet. The blood samples used in the ALA analysis of Fretts et al were collected in 1992 to 1993, a time at which the likelihood of finding an elderly cohort consuming the highest sources of ALA (chia and flax meal, or a diet high in greens and berries, which have a significant ALA content and a favorable n3 to n6 ratio), was very unlikely. In their study, median ALA levels were only 0.1per cent (quartile 1) to 0.23 per cent (quartile 4) of total plasma fatty acids. In contrast, LA constituted 20 per cent of total plasma phospholipid fatty acids. In a recent study evaluating the impact of a short term treatment with supplemental n 3 PUFA on the incidence of AF following cardiac surgery, we found that the mean total plasma n3 to n 6 ratios were about 0.1. This means that there was on average 10 times more n 6 PUFA in the plasma than n 3 PUFA. For ALA to have a meaningful impact on long chain n 3 PUFA levels, the amount of n 6 PUFA that is consumed must be reduced and the amount of ALA consumed in the diet must be increased. ALA is found in the chloroplasts of green leaves and in certain seeds. Although ALA is the most abundant fat on earth, the public is mostly unaware that they can consume large amounts of ALA that add up by eating plenty of greens, berries of all kinds, and especially the ALA rich foods like chia and flax meal. If they are unaware of the best sources of ALA, then it is unlikely they will consume enough to make a difference with respect to their risk of AF. Diets that reduce the intake of competing oils and increase the consumption of ALA rich plant products have been shown to significantly reduce the levels of biomarkers associated with risk of cardiovascular disease. What do these high ALA, low n 6 PUFA diets have in common? Might they offer a viable and sustainable strategy for reducing the risk of AF? 2013 is a different world from the 1992 to 1993 world sampled in the Fretts’ study. There is an active and growing grass roots, patient driven movement underway that recognizes the health benefits of a plant based diet, with an increasing number of authoritative physician and dietitian led websites, recipe sites, and social media support groups available to both educate and sustain the necessary dietary changes. Both authors of this editorial have experienced significant weight loss and seen personal improvements in cardiovascular biomarkers while following a plant based diet, and have found it easy to follow. Additional benefits of these diets include weight loss and improvements in blood pressure both of which are significant risk factors for AF. In summary, we conclude that, while the study of Fretts did not detect a relationship between ALA intake and risk of AF, systematic studies are needed to monitor the impact of diets that enhance ALA intake and promote its conversion to DHA. Only under these conditions can we rigorously determine whether dietary ALA has an impact on AF burden and AF progression. William Lands is a pioneer in the systematic study of n 3 and n 6 physiology and biochemistry with more than 50 years experience in this field. In 1980, Dr. Lands and colleagues demonstrated that treatment with a diet containing high levels of EPA per DHA (from fish oil) decreased the incidence of ventricular arrhythmia following experimental myocardial infarction and reduced the size of the infarction. Them authors suggest that adoption of a plant based diet rich in ALA may be one of the most sustainable and cost effective ways to accomplish this goal. Future studies will determine if such a diet has an impact on incident AF. (Editors summary)
Many studies in the past 50 years have shown that dietary lipids can modulate the progression of coronary artery disease, heart failure, and cardiac arrhythmogenesis. While fish are the most concentrated natural source of EPA and DHA, alpha linolenic acid (ALA) is the most abundant plant based n3 PUFA. Can dietary consumption of ALA, an abundant, sustainable and inexpensive n3 PUFA, lower the risk of AF in the same manner that consumption of fish and DHA appear to do? Fretts and colleagues directly address this important question. They use an epidemiologic approach to assess the relationship between plasma ALA levels, dietary ALA consumption, and AF risk. In their study of 2899 subjects (65 years or older at study entry), there were 707 cases of incident AF during a 15 to 16 year (nearly 30 000 person years) follow up. No relationship was detected between plasma ALA and incident AF after correcting for age, sex, and a variety of clinical and demographic factors. Strengths of the study include the size and age of the population, and the relatively large fraction of incident AF. Their results are consistent with an epidemiologic analysis suggesting that from age 40, there is approximately a 25 per cent lifetime risk of developing AF for both men and women. Technical weaknesses of the study include the measurement of plasma ALA levels at only a single time point, and the reliance on food questionnaires to assess the level of dietary ALA consumption. What are the implications of this study? The authors have concluded that neither ALA consumption nor plasma ALA levels are associated with AF risk. On the basis of their data, this seems to be a reasonable analysis and summary for their study. However, we argue that the conclusion that ALA consumption is not related to AF risk is premature as a general statement. It is interesting to note that a similar epidemiologic study has recently reported a beneficial impact of dietary ALA with respect to risk of heart failure. AF and heart failure are frequently comorbid conditions. It seems likely that diets that substantially increase consumption of ALA while decreasing the intake of n6 PUFA will have a beneficial impact on cardiovascular morbidity and mortality. However, optimal testing of this hypothesis would require careful longitudinal analysis of a cohort of patients with serial assessment of plasma PUFA levels, cardiovascular biomarkers, cardiac function, and electrophysiology. Most enzymes that metabolize PUFAs do not distinguish between n3 and n6 isoforms. The rate of conversion is dependent on the relative abundance of each substrate. If the n 6 PUFAs are abundant, the conversion of short chain to long chain n3 PUFAs will be inhibited. Short chain PUFA such as ALA and linolenic acid (LA, n 6) are converted to long chain PUFA (eg., arachidonic acid [AA], EPA, DHA) by elongase and desaturase enzymes. The rate of conversion of ALA to EPA and DHA thus depends on the ratio of n3 to n 6 PUFA in the diet. The blood samples used in the ALA analysis of Fretts et al were collected in 1992 to 1993, a time at which the likelihood of finding an elderly cohort consuming the highest sources of ALA (chia and flax meal, or a diet high in greens and berries, which have a significant ALA content and a favorable n3 to n6 ratio), was very unlikely. In their study, median ALA levels were only 0.1per cent (quartile 1) to 0.23 per cent (quartile 4) of total plasma fatty acids. In contrast, LA constituted 20 per cent of total plasma phospholipid fatty acids. In a recent study evaluating the impact of a short term treatment with supplemental n 3 PUFA on the incidence of AF following cardiac surgery, we found that the mean total plasma n3 to n 6 ratios were about 0.1. This means that there was on average 10 times more n 6 PUFA in the plasma than n 3 PUFA. For ALA to have a meaningful impact on long chain n 3 PUFA levels, the amount of n 6 PUFA that is consumed must be reduced and the amount of ALA consumed in the diet must be increased. ALA is found in the chloroplasts of green leaves and in certain seeds. Although ALA is the most abundant fat on earth, the public is mostly unaware that they can consume large amounts of ALA that add up by eating plenty of greens, berries of all kinds, and especially the ALA rich foods like chia and flax meal. If they are unaware of the best sources of ALA, then it is unlikely they will consume enough to make a difference with respect to their risk of AF. Diets that reduce the intake of competing oils and increase the consumption of ALA rich plant products have been shown to significantly reduce the levels of biomarkers associated with risk of cardiovascular disease. What do these high ALA, low n 6 PUFA diets have in common? Might they offer a viable and sustainable strategy for reducing the risk of AF? 2013 is a different world from the 1992 to 1993 world sampled in the Fretts’ study. There is an active and growing grass roots, patient driven movement underway that recognizes the health benefits of a plant based diet, with an increasing number of authoritative physician and dietitian led websites, recipe sites, and social media support groups available to both educate and sustain the necessary dietary changes. Both authors of this editorial have experienced significant weight loss and seen personal improvements in cardiovascular biomarkers while following a plant based diet, and have found it easy to follow. Additional benefits of these diets include weight loss and improvements in blood pressure both of which are significant risk factors for AF. In summary, we conclude that, while the study of Fretts did not detect a relationship between ALA intake and risk of AF, systematic studies are needed to monitor the impact of diets that enhance ALA intake and promote its conversion to DHA. Only under these conditions can we rigorously determine whether dietary ALA has an impact on AF burden and AF progression. William Lands is a pioneer in the systematic study of n 3 and n 6 physiology and biochemistry with more than 50 years experience in this field. In 1980, Dr. Lands and colleagues demonstrated that treatment with a diet containing high levels of EPA per DHA (from fish oil) decreased the incidence of ventricular arrhythmia following experimental myocardial infarction and reduced the size of the infarction. Them authors suggest that adoption of a plant based diet rich in ALA may be one of the most sustainable and cost effective ways to accomplish this goal. Future studies will determine if such a diet has an impact on incident AF. (Editors summary)
