Are statins and omega-3s incompatible?
Posted on June 18, 2013 by Dr. Davis
French researcher, Dr. Michel de Lorgeril, has been in the forefront of thinking and research into nutritional issues, including the Mediterranean Diet, the French Paradox, and the role of fat intake in cardiovascular health. In a recent review entitled Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3?, he explores the question of whether statin drugs are, in effect, incompatible with omega-3 fatty acids.
Dr. Lorgeril makes several arguments:
1) Earlier studies, such as GISSI-Prevenzione, demonstrated reduction in cardiovascular events with omega-3 fatty acid supplementation, consistent with the biological and physiological benefits observed in animals, experimental preparations, and epidemiologic observations in free-living populations.
2) More recent studies (and meta-analyses) examining the effects of omega-3 fatty acids have failed to demonstrate cardiovascular benefit showing, at most, non-significant trends towards benefit.
He points out that the more recent studies were conducted post-GISSI and after agencies like the American Heart Association’s advised people to consume more fish, which prompted broad increases in omega-3 intake. The populations studied therefore had increased intake of omega-3 fatty acids at the start of the studies, verified by higher levels of omega-3 RBC levels in participants.
In addition, he raises the provocative idea that the benefits of omega-3 fatty acids appear to be confined to those not taking statin agents, as suggested, for instance, in the Alpha Omega Trial. He speculates that the potential for statins to ablate the benefits of omega-3s (and vice versa) might be based on several phenomena:
–Statins increase arachidonic acid content of cell membranes, a potentially inflammatory omega-6 fatty acid that competes with omega-3 fatty acids. (Insulin provocation and greater linoleic acid/omega-6 oils do likewise.)
–Statins induce impaired mitochondrial function, while omega-3s improve mitochondrial function. (Impaired mitochondrial function is evidenced, for instance, by reduced coenzyme Q10 levels, with partial relief from muscle weakness and discomfort by supplementing coenzyme Q10.)
–Statins commonly provoke muscle weakness and discomfort which can, in turn, lead to reduced levels of physical activity and increased resistance to insulin. (Thus the recently reported increases in diabetes with statin drug use.)
Are the physiologic effects of omega-3 fatty acids, present and necessary for health, at odds with the non-physiologic effects of statin drugs?
I fear we don’t have sufficient data to come to firm conclusions yet, but my perception is that the case against statins is building. Yes, they have benefits in specific subsets of people (none in others), but the notion that everybody needs a statin drug is, I believe, not only dead wrong, but may have effects that are distinctly negative. And I believe that the arguments in favor of omega-3 fatty acid supplementation, EPA and DHA (and perhaps DPA), make better sense.
- See more at: http://blog.trackyourplaque.com/2013/06/are-statins-and-omega-3s-incompatible.html
Showing posts with label omega-3 fatty acids. Show all posts
Showing posts with label omega-3 fatty acids. Show all posts
Tuesday, June 18, 2013
Saturday, June 8, 2013
Dietary Fats and Health - Lawrence
Dietary Fats and Health: Dietary Recommendations in the Context of Scientific Evidence1
Abstract
Although early studies showed that saturated fat diets with very low levels of PUFAs increase serum cholesterol, whereas other studies showed high serum cholesterol increased the risk of coronary artery disease (CAD), the evidence of dietary saturated fats increasing CAD or causing premature death was weak. Over the years, data revealed that dietary saturated fatty acids (SFAs) are not associated with CAD and other adverse health effects or at worst are weakly associated in some analyses when other contributing factors may be overlooked. Several recent analyses indicate that SFAs, particularly in dairy products and coconut oil, can improve health. The evidence of ω6 polyunsaturated fatty acids (PUFAs) promoting inflammation and augmenting many diseases continues to grow, whereas ω3 PUFAs seem to counter these adverse effects. The replacement of saturated fats in the diet with carbohydrates, especially sugars, has resulted in increased obesity and its associated health complications. Well-established mechanisms have been proposed for the adverse health effects of some alternative or replacement nutrients, such as simple carbohydrates and PUFAs. The focus on dietary manipulation of serum cholesterol may be moot in view of numerous other factors that increase the risk of heart disease. The adverse health effects that have been associated with saturated fats in the past are most likely due to factors other than SFAs, which are discussed here. This review calls for a rational reevaluation of existing dietary recommendations that focus on minimizing dietary SFAs, for which mechanisms for adverse health effects are lacking.
Introduction
Since the Framingham Heart Study reported that high serum cholesterol was a major risk factor for coronary heart disease (1), there has been an aggressive campaign in the medical community to decrease serum cholesterol. It has been a widely accepted belief that dietary saturated fats and dietary cholesterol cause an increase in serum total cholesterol, as well as LDL-cholesterol (LDL-C)2 and thereby increase the risk of heart disease if consumed (2). Over the years, it became clear that high levels of LDL circulating in the blood are susceptible to lipid peroxidation, which results in the oxidized LDL being scavenged by macrophages lining certain arteries, particularly around the heart, leading to atherosclerosis (3). Although this mechanism provides a role for high serum LDL-C causing atherosclerosis, evidence of the involvement of saturated fats is lacking, even though it is well established that a diet high in saturated fat increases serum cholesterol and a diet high in polyunsaturated oil decreases serum cholesterol (4, 5). In fact, PUFAs are the components that are oxidized and generate antigenic substances that are recognized by immune cells for clearance of oxidized LDL in atherogenesis (6–8).
Numerous reports and reviews in recent years have begun to call the perceived pernicious effects of dietary saturated fatty acids (SFAs) into question. The purpose of this review is to summarize the scientific understanding as it relates to dietary fats in health and disease, particularly with regard to the innocuous nature of SFAs and the physiological effects that have implicated PUFAs in numerous disorders and diseases. The role of dietary fats in cardiovascular disease (CVD) and many other diseases is complex, yet there is a powerful inertia that has allowed the saturated fat doctrine to endure.
Dietary fatty acids and serum cholesterol
Dietary fat studies in the mid-20th century stressed the relationship of dietary SFAs and PUFAs to serum cholesterol levels with an aim toward decreasing the likelihood of the development of coronary artery disease (CAD) and premature death (4, 5). Once lipoprotein fractions were separated in the blood, it became evident that LDL and VLDL were the carriers of cholesterol that were most closely associated with risk of heart disease (9). Later it was found that the ratio of total serum cholesterol to HDL-C was a better indicator of heart disease risk (10). By the 1990s, the mechanisms by which dietary fats and specific types of fatty acids were regulating serum cholesterol and lipoproteins were beginning to be revealed.
A family of proteins known as sterol regulatory element binding proteins (SREBPs) were discovered in the early 1990s. These proteins move to the nucleus in cholesterol-depleted cells to alter transcription of several genes involved in lipid metabolism (11). When intracellular cholesterol levels are low, SREBP-1 promotes expression of genes for synthesis of cholesterol and LDL receptors that remove cholesterol from the circulation. When intracellular cholesterol levels are high, SREBP-1 is not activated by protease cleavage, and the genes for cholesterol production and LDL receptors are downregulated. SREBP-1 also activates promoters for genes involved in fatty acid synthesis and lipid storage (12). PUFAs, particularly docosahexaenoic acid and others to a lesser extent, regulate expression of the SREBP genes (13, 14). Consequently, when PUFAs are present, there is less expression of SREBPs and enzymes for cholesterol synthesis, and the serum cholesterol pool decreases.
There appears to be a number of proteins that bind PUFAs and are involved in regulating gene expression, including a family of G protein–coupled receptors (15), as well as peroxisome proliferator–activated receptors-α and -γ, retinoid X receptors, and various other nuclear receptors (16). The liver uses a variety of these receptors or sensors for PUFAs to regulate storage and utilization versus oxidation of PUFAs (17). In this way, PUFAs can stimulate fatty acid oxidation in the liver to minimize their potential for free radical oxidation in the body when their levels are high in the diet. One must keep in mind that this complex array for regulation of expression of a wide range of genes is also subject to an even more complex array of responses to dietary PUFAs and other dietary factors.
Single nucleotide polymorphisms in genes for many of the above factors, as well as in genes for several apolipoproteins, TNFs, glutathione peroxidases, and other proteins result in a wide range of individual responses to dietary constituents. The consequences of such genetic variation can be either little change or very large changes in serum lipids and lipoproteins in response to diet, depending on an individual’s genetic makeup (18). However, one should not lose sight of the fact that levels of many other proteins are being altered in the process, which can give rise to a wide array of physiological responses that influence susceptibility to many unhealthy conditions, such as CVD and cancer.
Short-chain SFAs, such as those in dairy fat and coconut oil, can also influence gene expression via interactions with various G protein–coupled receptors that are linked to several hormonal responses, including insulin and leptin, that regulate overall energy metabolism in the body (19). It is clear that there are numerous sensors that respond to dietary PUFAs and short- or medium-chain SFAs (20).
Genetic factors
Brown and Goldstein (21) received the Nobel Prize in Physiology or Medicine in 1985 for their work on genetic defects in LDL receptors of people with familial hypercholesterolemia (FH). They identified several mutations that produce nonfunctional LDL receptors, resulting in death from atherosclerosis and heart disease at an early age. Individuals with FH have serum LDL-C in excess of 300 mg/dL (or 8 mmol/L), although LDL-C may be as high as 650 mg/dL (17 mmol/L) in homozygous individuals. Goldstein and Brown (22) also identified several genes that code for other proteins involved in cholesterol transport and metabolism, such as apolipoprotein B-100 (apo B), which is a component of LDL that binds to LDL receptors. There are other proteins involved in LDL synthesis, transport, and clearance that can result in a genetic predisposition to increased serum LDL cholesterol and FH (23–25).
In the early 1990s, it was discovered that men with CVD tended to have smaller HDL particles than healthy controls (26). It was later found that LDL particle size was also significantly smaller in men with CAD than in case-matched controls (27), although another study showed the ratio of total serum cholesterol to HDL-C was a better predictor of CAD risk than LDL particle size (28). A prospective, population-based cohort study also found an increased risk of CAD in middle-aged men with smaller, dense LDL particles than in men with larger LDL particles, although the relationship did not show a linear dependence on particle size (29). It later became evident that LDL particle size was influenced by several factors and was not necessarily a useful predictor of heart disease risk; the nature of LDL is influenced by both dietary and genetic factors (30).
Lipoprotein (a) [Lp(a)] is a complex lipoprotein that has several properties in common with LDL. Like LDL and VLDL, Lp(a) contains apo B, but also contains highly variable forms of apolipoprotein(a) that strongly influence its atherogenicity and propensity to promote heart disease (31). The wide array of apolipoprotein(a) isoforms present in the human population may have caused some confusion regarding the role of Lp(a) in atherogenesis and CVD. The association of apo B with oxidized phospholipids was found to be dependent on Lp(a) (32). The presence of oxidized phospholipids and Lp(a) tend to be proinflammatory and promote atherogenesis.
Small, dense LDL particles rarely occur as an isolated condition, but are often associated with a specific phenotype that is characterized by hypertriglyceridemia, low HDL-C, abdominal obesity, insulin resistance, and other metabolic irregularities that lead to endothelial dysfunction and susceptibility to thrombosis (33). Small, dense LDL is also more susceptible to lipid peroxidation due to changes in the lipid composition, making it more atherogenic (34). LDL particles from the atherogenic phenotype contain less cholesterol and phospholipid, but more triglyceride. This phenotype is generally referred to as phenotype B and is characterized by elevated levels of apo B, which is found in LDL and VLDL (35).
There have been a host of proteins linked to lipoprotein metabolism and transport and a wide range of genetic variations identified that result in alterations of those proteins. Many are associated with HDL and larger HDL particle size, which is consistently associated with a decreased risk of CAD (36). HDL is important in reverse-cholesterol transport, bringing cholesterol from arterial deposits to the liver for processing, where it is converted to useful metabolites and eventually cleared from the body via bile secretions. A family of lipoprotein lipases, including hepatic lipase and endothelial lipase, are intimately involved in HDL metabolism. Endothelial lipase is upregulated during inflammation, a condition that increases LDL oxidation and atherogenesis (37). Genetic variation in apolipoprotein A-I, a major protein component of HDL, can result in larger but less stable HDL particles and decreased levels of circulating HDL (38). Cholesteryl ester transfer protein is generally considered to be protective, although this protein may transfer lipids from HDL to other lipoproteins that result in a less desirable serum lipid profile (39). HDL is emerging as a fascinating lipoprotein with a complex array of functions that involve both protein and lipid components. HDL has been found to influence immune function, vascular inflammation, glucose metabolism, and platelet function as well as other physiological phenomena unrelated to CVD (40).
Paraoxonase 1 (PON1) is another protein associated with HDL that exhibits esterase and lactonase enzyme activity, including metabolism of toxic organophosphorus pesticides and oxidized lipids in oxidized LDL particles. The levels of PON1 activity varies tremendously among humans, which depends to a large degree on genetic variation. However, environmental factors, such as dietary antioxidant consumption, alcohol consumption, and certain drugs can also influence PON1 activity (41). Dietary olive oil can increase levels of serum PON1 in some individuals, which is genotype dependent (42), whereas MUFAs and PUFAs can inhibit PON1 enzymatic activity (43). SFAs (palmitic and myristic) had virtually no effect on PON1 enzymatic activity. A recent study found that HDL isolated from patients with CAD lacks endothelial anti-inflammatory properties, has lower PON1 enzyme activity, and does not promote endothelial nitric oxide production (44), all of which are most likely tied to genetic rather than dietary factors.
Fatty acids involved in atherogenesis and CVD
Linoleic acid makes LDL more susceptible to lipid peroxidation and subsequent deposition of the oxidized LDL in macrophages lining the arteries (45). Several lipid peroxidation products have been shown to trigger transformation of circulating monocytes to macrophages that line the arteries and ultimately become foam cells (46, 47). Lipid peroxidation products also signal cells in the arterial intima to encapsulate foam cells by surrounding them with extracellular matrix proteins and eventually calcify the matrix (48). It would stand to reason that a greater abundance of PUFAs, relative to SFAs and MUFAs, during conditions of oxidative stress would provoke atherogenesis. The fibrous cap that is formed over fatty deposits makes them inaccessible to apolipoproteins such as apolipoprotein A-I or E, which are components of HDL, the lipoprotein that removes cholesterol from these deposits (49). The protein cap is characteristic of advanced atherosclerotic plaque and erosion of this protective cap by extracellular metalloproteases can release collagen and collagen-like fragments that trigger blood platelets to initiate a blood clot, which results in myocardial infarction or stroke (3).
Because saturated fats are not susceptible to lipid peroxidation, they have not been found to be involved in these mechanisms. This begs the question of how dietary polyunsaturated oils seem to lower the risk of CAD, even though many studies have shown no such effect. One important consideration is that foods that are considered sources of predominantly saturated fats, such as meats, are often cooked at high temperatures, which can induce lipid peroxidation in the minor amounts of PUFAs present in those animal products (50–52). Oxidative stress and lipid peroxidation products are known to promote heart disease, cancer, and several other chronic diseases (53, 54). High-temperature cooking can also oxidize carbohydrates, producing a range of toxic oxidation products that promote oxidative stress, type 2 diabetes, and CVD (55). The preparation and cooking methods used for foods that are traditionally classified as saturated fat foods may be producing substances from PUFAs and carbohydrates in those foods that are promoting disease.
Human food preferences tend to favor foods with both fats and sugar (56), which complicates any attempts to correlate saturated fats with disease. Sugars readily undergo oxidation, with fructose generally getting oxidized many times faster than glucose, whereas sucrose is relatively resistant to oxidation (57). The oxidation products of these monosaccharides include glyoxal, methylglyoxal, and formaldehyde. Methylglyoxal has been shown to promote endothelial dysfunction as well as hypercholesterolemia in rats (58). Methylglyoxal is also associated with increased atherosclerosis and hypertension in humans (59). Formaldehyde and methylglyoxal have been implicated in endothelial injury, oxidative stress, and angiopathy (60).
Many clinical studies show that there are fewer coronary events when polyunsaturated oils replace saturated fats in the diet (61). However, a recent meta-analysis found that interventions using mixed ω3 and ω6 PUFAs resulted in a significant (22%) decrease in CAD events compared with control diets with fewer PUFAs. However, interventions that used ω6 polyunsaturated oils with no ω3 PUFAs showed ∼16% more cardiovascular events compared with the control diets, although the increased number was not statistically significant (62). It would seem that even moderate amounts of ω3 PUFAs in the diet result in attenuation of inflammatory responses that are reflected in the significant reduction in coronary events observed with increasing dietary PUFAs. Of the common vegetable oils, soy oil contains ∼7% ω3 PUFAs and canola oil as much as 10% ω3 PUFAs, whereas corn, safflower, and sunflower oils generally contain <1 a="" class="xref-bibr" href="http://advances.nutrition.org/content/4/3/294.long#ref-63" id="xref-ref-63-1" pufas="">63
Lipid peroxidation and inflammation
Lipid peroxidation is invoked as a mechanism for numerous adverse health effects, such as aging, cancer, atherosclerosis, and tissue necrosis. The greater in vivo susceptibility of ω6 PUFAs relative to the ω3 PUFAs, has placed the spotlight on these fatty acids as contributing to or exacerbating many ailments (68). The metabolism of arachidonic acid to bioactive eicosanoids is responsible for many of the biological processes that lead to inflammation. Indeed, steroidal and nonsteroidal anti-inflammatory drugs suppress inflammation by blocking the release of arachidonic acid from membranes or its subsequent metabolism to eicosanoids.
Studies of inflammation in rats have found that dietary manipulation of relative amounts of ω6 PUFA precursors can have profound effects on the degree of inflammation. Predominantly SFAs in the diet result in far less inflammation than diets with either ω3 (69) or ω6 PUFAs (70). Several studies have shown that dietary supplementation with ω3 PUFAs can reduce inflammation and make patients less dependent on drug therapy to manage the pain and stiffness of arthritis (71–73). Patients should be advised to minimize their intake of ω6 oils when attempting ω3 supplementation as a therapeutic approach to reduce the inflammation of arthritis and other inflammatory syndromes (74, 75). Small amounts of ω3 supplements in a sea of dietary ω6 oils would have relatively little chance of changing the course of an inflammatory response. Because dietary saturated fats do not promote inflammation, it may be wiser to minimize ω6 PUFAs and consume more SFAs to reduce various types of inflammation; most sources of MUFAs contain significant amounts of PUFAs as well. There have been few scientific studies along these lines because of the misguided concern that saturated fats, even those from vegetable sources such as palm and coconut oil, would be detrimental to one’s health.
The efficacy of ω3 supplements for inflammatory syndromes other than rheumatoid arthritis are less persuasive, although study designs are questioned regarding whether patients are advised to reduce their ω6 fatty acid intake (76). Fish oil supplements improved pulmonary function in some asthmatics (responders) but not in others (nonresponders). A relatively high ratio (10:1) of dietary ω6 to ω3 PUFAs resulted in diminished respiratory function in methacholine-provoked asthmatics, whereas a lower ratio (2:1) produced significant improvement in >40% of the study participants (77). A study in Japan showed beneficial effects of ω3 supplements in asthmatic children in a controlled hospital ward environment (78). A comparison of dietary saturated fats with polyunsaturated oils was not found in the literature for asthma studies. Such an approach would be logical for this life-threatening condition, in view of the benign nature of saturated fats and the fact that carbohydrates, especially sugars, may actually be augmenting the incidence of asthma (79).
Are low-fat, low-saturated fat diets healthier?
Studies with laboratory animals have shown that high-fat diets promote chemically induced cancers (80, 81). A study of chemically induced mammary tumors in rats found that ω6 PUFAs promoted tumor proliferation, whereas saturated fats or ω3 PUFAs did not promote tumors as much or even suppressed tumors, depending on what one uses as a reference (82, 83). Although 1 review and meta-analysis found that linoleic acid, the predominant ω6 fatty acid in vegetable oils, is not a risk factor for breast, colorectal, and prostate cancers in humans (84), there is evidence to the contrary that high intake of ω6 relative to ω3 PUFAs increases cancer risks (85–87). There are multiple processes by which ω6 fatty acids can promote carcinogenesis; production of bioactive eicosanoids from arachidonic acid is 1 mechanism (88, 89). Nonsteroidal anti-inflammatory drugs as well as cyclooxygenase-2 inhibitors can suppress tumors by inhibiting production of prostaglandins, particularly those of the ω6 variety (90). Lipid peroxides are also known to promote chemically induced tumors (91), and PUFAs are highly susceptible to lipid peroxidation.
Investigators often seem to have a particular bias against saturated fats. One report showed that red meat alone was not significantly associated with colorectal cancer, although there was some increase in colorectal cancers with higher red meat intake [HR = 1.17 for highest vs. lowest intakes (95% CI = 0.92–1.49, P-trend = 0.08)]. Processed meats were significantly associated [HR = 1.42 (95% CI = 1.09–1.86, P-trend = 0.02)]. The authors then combined the data for red meat and processed meat to give a significant association and concluded that red and processed meat are positively associated with colorectal cancer (92). When specific types of meat were analyzed, significant risk was associated with pork [HR = 1.18 (95% CI = 0.95–1.48, P-trend = 0.02)] and lamb [HR = 1.22 (95% CI = 0.96–1.55, P-trend = 0.03)], but not with beef/or veal [HR = 1.03 (95% CI = 0.86–1.24, P-trend = 0.76)]. It is interesting to note that in 1 study, beef had a much lower ratio of PUFAs to SFAs than pork, but nearly the same ratio of PUFAs to SFAs as sheep (93). The ratio of MUFAs to SFAs in beef also varies, as it does in most meats, with the ratio ranging from ∼0.8 to 1.8, depending on breed and feeding practices (94).
Nitrite used in the preservation of many processed meats is known to form a carcinogen with secondary amines under acidic conditions that would prevail in the stomach (95). Others have found no association of red meat and only a very weak association of processed meat with breast cancer (96) and prostate cancer (97). Most studies find no differences in cancer risk with different types of fat, but do find associations with high levels of fat in the diet (81).
A recent meta-analysis (98) reviewed 20 studies with >1 million subjects and found that red meat was not associated with CAD events [RR = 1.00 (95% CI = 0.81–1.23, P-trend = 0.36)]. In contrast, processed meats were associated with increased incidence of CAD [RR = 1.42 (95% CI = 1.07–1.89, P-trend = 0.04)]. This indicates that saturated fat per se is not increasing CAD events, but other factors are, such as preservatives used in processed meats or other dietary substances that are being consumed in conjunction with processed meats. It is important to keep in mind that meats generally contain as much MUFA as SFA. Others are beginning to challenge the saturated fat hypothesis with closer analyses of past studies (99–103).
Campaigns were waged against tropical oils (palm and coconut oils) in the early 1980s because of their high levels of SFAs, even though palm oil contains about as much MUFAs acids as SFAs and has an ample amount of PUFAs to keep serum cholesterol low. In fact, 2 studies showed that the higher ratio of SFAs to MUFAs in palm oil (1.1:1) compared with olive oil (0.22:1) had no effect on serum lipids in healthy volunteers (104, 105). Palm oil and olive oil have similar amounts (∼10%) of PUFAs. SFAs in coconut oil increase serum HDL-C more than LDL-C to give a more favorable lipid profile relative to dietary carbohydrates (10). Claims that tropical oils with a high SFA content increase the risk of CAD lack clear scientific evidence to that effect. Indeed, countries with high intake of tropical oils have some of the lowest rates of heart disease in the world (106).
Many of the shorter chain fatty acids found in milk fat and coconut oil have beneficial health effects. The shorter chain SFA in milk (C4–C12) are not only metabolized rapidly for energy in infants, but have been found to have important antiviral, antimicrobial, antitumor, and immune response functions (107). Lauric acid, which is present in milk and the most abundant fatty acid in coconut oil, is effective in preventing tooth decay and plaque buildup (108). Diets rich in coconut oils have also been shown to lower other risk factors for CAD, such as tissue plasminogen activator antigen and Lp(a) (109). The medium-chain SFAs in coconut oil and butterfat (milk) increase total serum cholesterol, but their positive effects on HDL-C are protective in many ways. There is also evidence that proteins, fats, and calcium in milk are beneficial in lowering blood pressure, inflammation, and the risk of type 2 diabetes (110, 111). Indeed, these constituents of milk have clear beneficial effects against metabolic syndrome, which is a major factor in promoting heart disease, as well as premature death from a variety of causes (112).
There has been a spate of recent publications in the biomedical literature that question the negative perception that dairy fats are bad for health. One meta-analysis showed that participants in prospective studies with the highest consumption of dairy products had a lower RR for all-cause mortality as well as for CAD, stroke, and diabetes compared with the lowest intake of dairy products (113). Many of the studies included in the analysis started before low-fat milk was available on the market. Another review arrived at the same conclusion that consumption of dairy products is not associated with higher risk of CVD (100). Although prospective cohort studies often find a significant reduction in the incidence of CAD with a larger ratio of PUFAs to SFAs in the diet (114), there are often many other factors related to overall health that correlate with the unsaturated to SFA ratio, such as exercise, a healthier lifestyle, and more fiber and less sugar in the diet.
Less fat generally means more carbohydrate
It should not be surprising that substitution of carbohydrates (starches) for saturated fats in the diet has relatively little effect on serum lipids. Excess carbohydrates are converted to fats for efficient energy storage, and the human body synthesizes primarily SFAs from excess carbohydrates, although MUFAs are also formed. Consequently, from a physiological viewpoint, there is no reason to believe that replacing fat in the diet with carbohydrate at a constant caloric intake will improve the serum lipid profile significantly. Indeed, a low-fat, high-carbohydrate diet causes an increase in serum triglycerides and small, dense LDL particles (115), which are more strongly associated with CAD than serum total cholesterol or LDL-C. When dietary fat is replaced by carbohydrate without changing the fatty acid composition of the fat, there is no change in LDL-C or HDL-C, but there is an increase in serum triglycerides (116). However, if there is a higher percentage of PUFAs and lower SFAs in a low-fat diet, serum total cholesterol and LDL-C will decrease (117).
Young children who consumed more fruit juice than their peers were shorter in stature and had greater BMI than their peers who drank less fruit juice (118). A trend of increased fruit juice consumption by infants and children in recent years has coincided with a decrease in milk consumption (119). The rates of childhood obesity have skyrocketed since the introduction of low-fat milk, although high fructose corn syrup (HFCS) became omnipresent in foods at the same time and is more strongly associated with obesity than dietary fat (120, 121). As stated previously, the short-chain SFAs in milk provide valuable antibacterial and antiviral activities, which would result in healthier children. The short-chain SFAs found in milk act as signaling agents in the immune system (122). Infections in children also correlated with higher levels of atherogenic oxidized LDL, as well as lower levels of HDL (123). It is possible that oxidized LDL and low HDL impart increased susceptibility to infection, although the combination of infections and an adverse serum lipid profile may both result from an undesirable diet, i.e., more sugar and fewer healthy fats.
Food processors generally add large amounts of sugar to fat-free or low-fat foods to make them more palatable to consumers. Fructose is 1 dietary constituent that is consistently found to have adverse health consequences, and the larger the proportion of fructose is in the diet, the more formidable the effect. The adverse effects of fructose that have been documented include increased serum triglycerides, particularly in men (124, 125); increased serum uric acid, which is associated with gout and hypertension (126); increased lipid peroxidation (57) and increased oxidation of LDL (127); increased oxidative stress in animal models (128); greater risk of the development of metabolic syndrome, including obesity, insulin resistance, hypertension, and CVD risk (129, 130); increased nonalcoholic fatty liver disease (131); and increased systemic inflammation and associated renal disease (132).
There are clearly many established physiological mechanisms by which fructose increases CVD and several other diseases. Whether the source of dietary fructose is sucrose or HFCS would seem irrelevant, although sucrose is 50% fructose, whereas the most common dietary source of HFCS (soft drinks) is generally 55% fructose and ∼43% glucose. Solutions of fructose are also highly susceptible to autoxidation, producing a host of toxic products (57), whereas sucrose is highly resistant to oxidation. The toxic products from fructose oxidation include formaldehyde and α-dicarbonyls. Although saturated fats have been implicated in many of the adverse health effects attributed to fructose, there is no scientific evidence to support a role for saturated fats in the physiological mechanisms. On the other hand, plausible mechanisms are proposed for all of the unhealthy conditions promoted by high fructose intake mentioned earlier.
It turns out that a high level of fructose in the diet increases plasma triglycerides, which leads to not only increased levels of VLDL and small, dense LDL particles, but increased levels of oxidized LDL, insulin resistance, and other metabolic consequences linked to metabolic syndrome and dyslipidemia (133). The mechanisms by which fructose promotes inflammation and elevated levels of uric acid and several cytokines have been reviewed (132).
Conclusions
Saturated fats are benign with regard to inflammatory effects, as are the MUFAs. The meager effect that saturated fats have on serum cholesterol levels when modest but adequate amounts of polyunsaturated oils are included in the diet, and the lack of any clear evidence that saturated fats are promoting any of the conditions that can be attributed to PUFA makes one wonder how saturated fats got such a bad reputation in the health literature. The influence of dietary fats on serum cholesterol has been overstated, and a physiological mechanism for saturated fats causing heart disease is still missing.
Various aldehydes produced in the oxidation of PUFAs, as well as sugars, are known to initiate or augment several diseases, such as cancer, inflammation, asthma, type 2 diabetes, atherosclerosis, and endothelial dysfunction. Saturated fats per se may not be responsible for many of the adverse health effects with which they have been associated; instead, oxidation of PUFAs in those foods may be the cause of any associations that have been found. Consequently, the dietary recommendations to restrict saturated fats in the diet should be revised to reflect differences in handling before consumption, e.g., dairy fats are generally not heated to high temperatures. It is time to reevaluate the dietary recommendations that focus on lowering serum cholesterol and to use a more holistic approach to dietary policy.
Acknowledgments
The sole author had responsibility for all parts of the manuscript.
Footnotes
- ↵1 Author disclosure: G. D. Lawrence, no conflicts of interest.
- ↵2 Abbreviations used: apo B; apolipoprotein B-100; CAD, coronary artery disease; CVD, cardiovascular disease; FH, familial hypercholesterolemia; HDL-C, HDL cholesterol; HFCS, high fructose corn syrup; LDL-C, LDL cholesterol; Lp(a), lipoprotein(a); PON1, paraoxonase 1; SFA, saturated fatty acid; SREBP, sterol regulatory element binding protein.
- © 2013 American Society for Nutrition
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Thursday, June 6, 2013
Fish Oil Triglycerides vs. Ethyl Esters: A comparative review of absorption, stability and safety concerns
Fish Oil Triglycerides vs. Ethyl Esters: A comparative review of absorption, stability and safety concerns
Media exposure, scientific findings, and word of mouth have lead to a significant increase in fish oil supplementation over the past five years. The popularity of these supplements has also lead to an increased concern over product quality. The term “pharmaceutical quality” is typically associated with fish oils that are highly refined; however, the use of this term is not regulated and can be freely used by any branded fish oil product. Most experts associate pharmaceutical quality with products that comply with a fish oil monograph developed by the Council for Responsible Nutrition (CRN). The CRN Monograph established strict limits for environmental contaminants and oxidative quality parameters. Although the CRN Monograph represents an important step forward in the standardization of high quality fish oil it does not address every issue relating to quality. In particular the monograph does not differentiate between lipid classes (molecular forms). Although a product label may say “Fish Oil”, the chances are the product is not an oil at all, rather it is an alternate lipid class called a fatty acid ethyl ester (FAEE) or just EE for short. This differs in molecular structure from authentic fish oil which has a chemical structure known as a triglyceride (TG).What are triglycerides?
The National Academy of Sciences defines fats and oils as “complex organic molecules that are formed by combining three fatty acids with one molecule of glycerol”. Triglycerides, or triacylglycerols, are the terms used to define this molecular structure combining three fatty acids (i.e. EPA and DHA) esterified (bonded) to a glycerol backbone. TGs are the natural molecular form that make up virtually all fats and oils in both animal and plants species. The omega-3 fats present in fish are almost exclusively TGs1. Because free fatty acids are rapidly oxidized the TG structure offers greater stability to the fatty acids and prevents breakdown and oxidation2.
What are ethyl esters, and how are they produced?
Fatty acid ethyl esters are a class of lipids that are derived by reacting free fatty acids with ethanol (alcohol)3. Called trans-esterification, the process involves a reaction whereby the glycerol backbone of a TG is removed and substituted with ethanol4. The resulting EE allow for the fractional distillation (concentration) of the long chain fatty acids at lower temperatures. Commonly referred to as molecular distillation in the fish oil industry this step allows for the selective concentration of the EPA and DHA fatty acids to levels greater than found naturally in fish3. The resulting EPA and DHA concentrate is typically the end product that is subsequently marketed and sold as “Fish Oil concentrate”. This situation presents several issues. Because the term fat or oil refers only to TG the EPA and DHA ethyl ester concentrate is, by definition, no longer a fat or oil and is incorrectly marketed as fish oil. Because EEs rarely occur in nature this affects the way they are digested and absorbed in the body.
Are all fish oil concentrates ethyl esters?
The vast majority of fish oil concentrates sold globally; including those sold in North America are EPA and DHA EE concentrates. A small percentage of fish oil concentrates on the market are natural TGs. In the manufacturing of EE concentrates it is possible to convert the fatty acids back to TGs using food grade enzymes. This process, called glycerolysis, removes the ethanol molecule and re-esterifies the EPA and DHA fatty acids to a glycerol backbone. These are commonly referred to as re-esterfied or concentrated triglycerides (rTGs). The process of converting EE to TG is uncommon due to cost constraints adding 30-40 % to the end bulk oil cost. Therefore, the only rationale for omitting the glycerolysis step is cost cutting.
Absorption and metabolism of natural triglycerides vs. ethyl esters
Dietary fish oil (triglycerides) is digested in the small intestine by the emulsifying action of bile salts and the hydrolytic activity of pancreatic lipase1,5. The hydrolysis of a TG molecule produces two free fatty acids (FFA) and a monoglyceride (one fatty acid combined to glycerol)1,5. These metabolic products are then absorbed by intestinal enterocytes and reassembled again as TGs1,5. Carrier molecules called chylomicrons then transport the TGs into the lymphatic channel and finally into the blood6. The digestion of EEs is slightly different due to the lack of a glycerol backbone1. In the small intestine it is again the pancreatic lipase that hydrolyzes the fatty acids from the ethanol backbone, however; the fatty acid-ethanol bond is up to 50 times more resistant to pancreatic lipase as compared to hydrolysis of TGs7,8. The EEs that get hydrolyzed produce FFA plus ethanol. The FFA’s are taken up by the enterocytes and must be reconverted to TGs to be transported in the blood1. The TG form of fish oil contains its own monoglyceride substrate; whereas EE fish oils, coupled to ethanol, do not. EE must therefore obtain a glycerol substrate from another source. Without a glycerol or monoglyceride substrate TG re-synthesis is delayed, suggesting that transport to the blood is more efficient in natural TG fish oils in comparison to EEs. Furthermore, this delay of TG re-synthesis in EE fish oils could cause an increase in free fatty acids and subsequent oxidation of those free fatty acids.
Bioavailability of triglycerides vs. ethyl ester fish oils
Numerous studies have assessed the absorption and bioavailability of EE fish oils. Most studies have measured the amount of EPA and DHA in blood plasma after ingestion of fatty acids as either TG or EE. Although a few studies have found that the absorption rate is similar between the two types of oils, the overall evidence suggests that TG fish oils are better absorbed in comparison to EE. Natural TG fish oil results in 50 % more plasma EPA and DHA after absorption in comparison to EE oils11, TG forms of EPA and DHA were shown to be 48 % and 36 % better absorbed than EE forms12, EPA incorporation into plasma lipids was found to be considerably smaller and took longer when administered as an EE13, plasma lipid concentrations of EPA and DHA were significantly higher with daily portions of salmon in comparison to 3 capsules of EE fish oil14 and in the rat, DHA TG supplementation led to higher plasma and erythrocyte DHA content than did DHA EE15 and a higher lymphatic recovery of EPA and DHA16.
One of the causative factors for the poor bioavailability of EE is a much greater resistance to digestive enzymes. As previously mentioned, during the digestive process, pancreatic lipase enzymes hydrolyse (cleave) the oils to liberate the fatty acids and EEs are much more resistant to this enzymatic process than the natural TG form7. A recent study assessed the specificity of five lipases towards EPA and DHA in TG and EE forms. All of the investigated lipases discriminated against both EPA and DHA more in EE than in the natural TG oils. In other words, both EPA and DHA were more easily hydrolysed from a TG than from an EE. EPA and DHA hydrolysis would be further compromised in individuals who suffer from a digestive disorder, such as pancreatic insufficiency. EEs should be avoided in such populations as they would likely cause malabsorption of EPA and DHA. Review of the existing literature provides evidence which, suggests that omega-3 fatty acids in the natural form of TGs are more efficiently digested and significantly better incorporated into plasma lipids in comparison to EE forms. Recently, two clinical trials have settled the debate of which fish oil form is more bio-available in humans; the ethyl ester (EE) versus the triglyceride (TG) form. The Dyerberg et al., 2010 study was done to demonstrate the differences in absorption levels of plasma EPA+DHA following consumption of various fish oil forms including EE and TG. They noticed that with about the same grand total of EPA+DHA administered to the EE and TG group compared to the placebo group, the EE form was given the lowest assimilation as a measure of bioavailability9. The mechanism of action was simple, in that, pancreatic lipase breaks down EE to a lesser extent than TG9. Since, the omega 3 fatty acid plasma profile can significantly be elevated with the consumption of TG versus EE fish oil; then clearly TG fish oil can be more effective. In another more recent study done by Neubronner et al., 2010 a similar comparison was made utilizing a different study design. A unique method of bio-availability was used (Omega 3 index) this method looks at the omega 3 FA (EPA+DHA) incorporated into the RBC membranes10. In comparison to the plasma levels measured in the Dyerberg et al., study, this method is even more specific because it can measure EPA+DHA at the level of the tissues10. Therefore, the outcome of this study showed a statistically significant incorporation of EPA+DHA in the RBC membranes via TG over EE by over 25 percent10. Therefore, in both of the above studies the overall bioavailability of omega 3 fatty acids with equal EPA+DHA in the form of TG showed to be more effective.
Ethyl ester fish oils are less stable, and readily oxidize
Omega-3 fatty acids in the form of EEs are much less stable than those in the natural TG form and readily oxidize. The oxidation kinetics of DHA as an EE or as a TG was assessed by measuring the concentration of oxygen found in the head space of a reaction vessel with both TG and EE forms17. The EE form of DHA was more reactive, and quickly oxidized, demonstrating that EEs are far less stable and can more readily produce harmful oxidation products17. Furthermore, the stability of phospholipid, triglyceride and EEs containing DHA has been assessed18. After a ten-week oxidation period, the EE DHA oil decayed 33 % more rapidly18.
Ethyl ester fish oil safety
During the digestive process, EEs are converted back to TGs by intestinal enterocytes1 which, results in the release of ethanol. Although the amount of ethanol released in a typical dose of fish oil is small, those with sensitivities to alcohol or those who are alcoholics should refrain from the consumption of EEs. Young children may also be more vulnerable to the toxic effects of ethanol even in small quantities. The exact amount of ethanol released from the EE fish oil is dependent on the exact profile of the fatty acids. For a typical 60 % omega-3 EE concentrate the amount of ethanol would be approximately 15 % by weight (see Figure 1). Additional concern exists regarding whether a small portion of EE
is absorbed directly into the body19. Unlike TGs, the presence of EEs in the body has been found to potentiate cytotoxicity19. Several in vitro studies using purified lysosomes20, purified mitochondria19 or intact Hep G2 cells22 have provided evidence for toxicity of EEs. Studies in animals have shown that ethanol released into the liver and pancreas can result in severe organ damage23. Post mortem organ analysis has demonstrated that EEs are toxic mediators of ethanol induced cellular injury24, and have been shown to induce pancreatic injuries when infused in vivo into rats25. It is possible that efficient EE digestion in the GI tract could prevent toxicity3, but until further studies carefully examine EE oxidation, the potential for direct uptake of EEs, or EE absorption into the circulation via the stomach, EEs should be consumed with caution.How can I determine if my fish oil is a natural triglyceride or an ethyl ester?
There is a simple, inexpensive and rapid method to determine if a fish oil supplement is in the TG or EE form by using polystyrene (Styrofoam) cups.
Method
Measure and place 20 ml of fish oil in a polystyrene cup. Place the cup on a plate to avoid any mess. Observe the cup after 10 minutes. If the fish oil has leaked significantly through the cup it contains EE. Due to their chemical composition, EE will actually eat straight through the polystyrene cup. This effect will become evident after just a few minutes; however, significant leakage is seen after 10 minutes. Natural TG fish oils placed in the same cup will not show leakage after 10 minutes. Natural TG fish oils may show leakage through the cup in very small amounts after 2-3 hours.
Conclusion
Fish oil supplements in the natural TG form offer numerous advantages when compared to those in the EE form: oils in a TG form are completely safe to consume, are naturally occurring, provide increased absorption, and are much more stable. Therefore, since TG fish oil can be more effectively absorbed then it can be potentially better at reaching therapeutic ranges in comparison to EE fish oil. While EEs are a source of omega-3 fatty acids, research shows that they are not as beneficial as TGs and additional research is required to fully assess potential toxicity. While some countries (e.g. Australia) have gone as far as banning the sale of EEs, other countries such as the US, Canada, and the UK allow the sale of the EE form and furthermore do not require any additionally labeling. These supplements are therefore often incorrectly labeled as “Fish Oil” and pose a risk to those who must avoid ingestion of alcohol.
| Studies comparing the absorption of triglyceride and ethyl ester Fish Oils Cod Liver Oil | |
| Hansen JB, Olsen JO, Wilsgard L, Lyngmo V, Svensson B. Comparative effects of prolonged intake of highly purified fish oils as ethyl ester or triglyceride on lipids, haemostasis and platelet function in normolipaemic men. Eur J Clin Nutr,47, 497-507. | 31 normolipaemic non-obese men (21-47 yrs) were given 4 g highly purified omega-3 ethyl ester fatty acids, 4 g corn oil as a placebo, or 12 g n-3 triglycerides for 7 weeks. The daily intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was 2.2 and 1.4 for TG, and 2.2 and 1.2 for EE. Blood samples were collected at week 1, 3 and 7. Comparison of time course incorporation of n-3 fatty acids in plasma phospholipids by repeated measures of variance did not show any difference between the TG and EE n-3 sources. Repeated measure ANOVA did however reveal a significant difference between TG and EE with respect to the incorporation of EPA into plasma cholesterol esters. Argument is made that higher amounts of omega-3 fatty acid lead to decreased differences between absorptions. Although higher doses of omega-3 fatty are not always realistic. |
| Beckermann B, Beneke M, Seitz I. 1990. Comparative bioavailability of eicosapentaenoic acid and docosahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers. Arzneimittelforschung, 40(6):700-4. | The bioavailability of EPA and DHA from triglycerides, free fatty acids and ethyl esters was investigated in 8 female volunteers in a randomized triple cross-over trial with baseline control. EPA/DHA was administered in capsules in form of triglycerides, free fatty acids and ethyl esters. The resulting EPA/DHA plasma levels were determined and evaluated. The mean relative bioavailability of EPA/DHA compared to triglycerides was 186/136 % from free fatty acids and 40/48 % from ethyl esters. Maximal plasma levels were about 50 % higher with free fatty acids and about 50 % lower with ethyl esters as compared to triglycerides. The tolerability of the free fatty acids was much worse than that of triglycerides and ethyl esters. The main side effect was eructation. |
| Krokan HE, Bjerve KS, Mork E. 1993. The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. Biochim Biophys Acta,1168, 59-67. | Enteral absorption by healthy male volunteers of EPA and DHA from an ethyl ester andnatural triglyceride fish oil was found to be similar after intake of equivalent doses, however; hydrolysis of natural triglyceride fish oil was more efficient. In spite of the similar serum levels of EPA and DHA obtained in vivo, in vitro hydrolysis by porcine pancreatic lipase of the ethyl ester was 3-fold slower than hydrolysis of a the triglyceride. Under similar conditions release of AA from triglyceride and ethyl ester was essentially similar and approx. 1.5-fold faster than release of EPA and DHA from ethyl esters. There are therefore differences in the rate of hydrolysis of ethyl ester and triglycerides fish oils. |
| el Boustani S, Colette C, Monnier L, Descomps B, Crastes de Paulet A, Mendy F. (1987). Enteral absorption in man of eicosapentaenoic acid in different chemical forms. Lipids, 10, 711-4. | After administering the equivalent of 1 g of EPA in four different chemical forms, the kinetics of EPA incorporation into plasma triglycerides were compared by gas liquid chromatography on a capillary column following separation of the lipid fraction by thin layer chromatography. EPA incorporation into plasma triglycerides was markedly smaller and later when EPA was administered as an ethyl ester rather than as EPA free fatty acid, EPA arginine salt or 1,3-dioctanoyl-2-eicosapentaenoyl glycerol. Our results and the data in the literature are compatible with the hypothesis that the glycerol form of EPA is absorbed with minimum hydrolysis and escapes random distribution between the other positions of the glycerol molecule during the absorption process. |
| Lawson LD, Hughes BG. (1988). Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters. Biochem Biophys Res Commun, 52, 328-35. | As triacylglycerols, eicosapentaenoic acid (1.00 g) and docosahexaenoic acid (0.67g) were absorbed only 68 % and 57 % as well as the free acids. The ethyl esters were absorbed only 20 % and 21 % as well as the free acids. The incomplete absorption of eicosapentaenoic and docosahexaenoic acids from fish oil triacylglycerols correlates well with known in vitro pancreatic lipase activity. |
| Visioli F, Rise P, Barassi MC, Marangoni F, Galli C. (2003). Dietary intake of fish vs. formulations leads to higher plasma concentrations of n-3 fatty acids. Lipids, 38, 415-8. | For six weeks, volunteers were given 100 g/d of salmon, or 1 or 3 capsules of ethyl ester fish oil/d. Marked increments in plasma EPA and DHA concentrations (microgram/mg total lipid) and percentages of total fatty acids were recorded at the end of treatment with either omega-3 capsules or salmon. Increments in plasma EPA and DHA concentration after salmon intake were significantly higher than after administration of capsules. The same increments would be obtained with at least two and nine-fold higher doses of EPA and DHA, respectively, if administered with capsules rather than salmon. We provide experimental evidence that natural omega-3 fatty acids from fish are more effectively incorporated into plasma lipids than when administered as capsules. |
| Valenzuela A, Valenzuela V, San hueza, J, Nieto S. (2005). Effect of supplementation with docosahexaenoic acid ethyl ester and sn-2 docosahexaenyl monoacylglyceride on plasma and erythrocyte fatty acids in rats. Ann Nutr Metab. 49, 49-53. | Female rats received a 40 day supplementation of either DHA ethyl ester or DHAmonoglycerate. Plasma and erythrocyte fatty acid composition were assessed by gas chromatography at day 0 and 40 of supplementation. DHA ethyl ester increased plasma and erythrocyte DHA by 15 and 11.9 %, respectively, with no modification of arachidonic acid (AA) con tent. DHA-monoglycerate supplementation increased plasma and erythrocyte DHA by 24 and 23.8 %, respectively, and reduced AA by 5.5 and 3 %, respectively. Although this data is done with animals, the authors conclude that in the rat, DHAmonoglycerate supplementation allows a higher plasma and erythrocyte DHA content than DHA-ethyl ester. |
| Ikeda I, Sasaki E, Yasunami H, Nomiyama S, Nakayama M, Sugano M, Imaizumi K, Yazawa K. (1995). Digestion and lymphatic transport of eicosapentaenoic and docosahexaenoic acids given in the form of triacylglycerol, free acid and ethyl ester in rats. Biochim Biophys Acta; 1259: 297-304. | Lymphatic transport of EPA and DHA with trieicosapentaenoyl glycerol (TriEPA) and tridocosahexaenoyl glycerol (TriDHA) was compared with the transport of ethyl ester and free acid in rats cannulated with thoracic duct. Trioleoylglycerol (TO) served as a control. Lymphatic recovery of EPA and DHA in rats given TriEPA and TriDHA was significantly higher at the first 3 h after the administration compared to those given as free acid or ethyl ester. The 24-h recovery was comparable between triacylglycerol (TAG) and free acid, while it was significantly lower in ethyl ester. The hydrolysis rate of ethyl esters was extremely low even in 6 h incubation with lipase. Although this data is done with animals, the authors conclude that there is less lymphatic recover of EPA and DHA when they are in ethyl ester form. |
| Nordoy A, Barstad L, Connor WE, Hatcher L. 1991. Absorption of the n-3 eicosapentaenoic and docosahexaenoic acids as ethyl esters and triglycerides by humans. Am J Clin Nutr. 53:1185-90. | Five normolipemic subjects received three test meals. 1) 40g n-3 triglycerides, 2) 28 g n-3 ethyl ester plus 12 g olive oil, 3) 28 g n-3 ethyl ester and 4) 40g olive oil. When equivalent amounts of fat were given, the increase in chylomicrons and plasma triglycerides was similar; n-3 fatty acid contents were also similar after n-3 fatty acid intake as ethyl esters or triglycerides. Ethyl esters alone were well absorbed and produced similar n-3 fatty acid responses in plasma triglycerides and chylomicrons. At 24 h after the n-3 fatty acid containing meals, the fatty acid plasma concentration of these acids was similar. This study suggests that n-3 fatty acids given as ethyl esters or triglycerides were equally well absorbed. However, the doses of fish oil given were unrealistically high thus one should be hesitant to draw conclusions from such data. |
| J Dyerberg , P Madsen , JM Moller ,I Aardestrup ,EB Schmidt. Bioavailability of marine n-3 fatty acid formations. Prostaglandins Leutkot. Essent. Fatty Acids 83 (2010),137-141. | Seventy- two volunteers were split into 6 groups 4 of which were double blinded and 2 of which were the EE and rTG groups. Each group was given approximately the same amount of fish oil 3.1-3.6 grams and then compared to a corn oil fed placebo group. Base line plasma cholesterol esters (CE), phospholipids (PL) and triglycerides (TG) were measured as the mean increase as a grand total of the EPA+DHA present and then taken again at the end of the two week period9. They noticed that with about the same grand total of EPA+DHA administered to the EE and rTG group compared to the placebo group, the EE form was given the lowest assimilation as a measure of bioavailability. Once adjusted for the results were 76% and 134% for the EE and rTG groups respectively. |
| J Neubronner , JP Schuchardt, G Kressel, M Merkel, C von Schacky and A Hahn. Enhanced increase of omega-3 index in response to long term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters. Eur. J. of Clin. Nutr.(2010),1-8. | The study randomized 150 subjects in one of three groups; two fish oil groups versus placebo. The two fish oil groups (EE and rTAG) had the exact amount of combined EPA+DHA per capsule and the total dose per day was 1.68grams. The two fish oil groups were compared to a corn oil placebo group and the duration of the study was 6 months. A unique method of bio-availability was used (Omega 3 index) this method looks at the omega 3 FA (EPA+DHA) incorporated into the RBC membranes. Therefore, the outcome of this study showed a statistically significant incorporation of EPA+DHA in the RBC membranes via re-esterified triacylglycerides (rTAG) over ethyl esters (EE) by more than a 25 percent. |
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Read thecomplete article here.
Wednesday, May 22, 2013
DHA: the crucial omega-3 - Davis
DHA: the crucial omega-3
Of the two omega-3 fatty acids that are best explored, EPA and DHA, it is likely DHA that exerts the most blood pressure- and heart rate-reducing effects. Here are the data of Mori et al in which 4000 mg of olive oil, purified EPA only, or purified DHA only were administered over 6 weeks:
□ indicates baseline SBP; ▪, postintervention SBP; ○, baseline DBP; •, postintervention DBP; ⋄, baseline HR; and ♦, postintervention HR.
In this group of 56 overweight men with normal starting blood pressures, only DHA reduced systolic BP by 5.8 mmHg, diastolic by 3.3 mmHg.
While each omega-3 fatty acid has important effects, it may be DHA that has an outsized benefit. So how can you get more DHA? Well, this observation from Schuchardt et al is important:
DHA in the triglyceride and phospholipid forms are 3-fold better absorbed, as compared to the ethyl ester form (compared by area-under-the-curve). In other words, fish oil that has been reconstituted to the naturally-occurring triglyceride form (i.e., the form found in fresh fish) provides 3-fold greater blood levels of DHA than the more common ethyl ester form found in most capsules. (The phospholipid form of DHA found in krill is also well-absorbed, but occurs in such small quantities that it is not a practical means of obtaining omega-3 fatty acids, putting aside the astaxanthin issue.)
So if the superior health effects of DHA are desired in a form that is absorbed, the ideal way to do this is either to eat fish or to supplement fish oil in the triglyceride, not ethyl ester, form. The most common and popular forms of fish oil sold are ethyl esters, including Sam’s Club Triple-Strength, Costco, Nature Made, Nature’s Bounty, as well as prescription Lovaza. (That’s right: prescription fish oil, from this and several other perspectives, is an inferior product.)
What sources of triglyceride fish oil with greater DHA content/absorption are available to us? My favorites are, in this order:
Ascenta NutraSea
CEO and founder, Marc St. Onge, is a friend. Having visited his production facility in Nova Scotia, I was impressed with the meticulous methods of preparation. At every step of the way, every effort was made to limit any potential oxidation, including packaging in a vacuum environment. The Ascenta line of triglyceride fish oils are also richer in DHA content. Their NutraSea High DHA liquid, for instance, contains 500 mg EPA and 1000 mg DHA per teaspoon, a 1:2 EPA:DHA ratio, rather than the more typical 3:2 EPA:DHA ratio of ethyl ester forms.
Pharmax (now Seroyal) also has a fine product with a 1.4:1 EPA:DHA ratio.
Nordic Naturals has a fine liquid triglyceride product, though it is 2:1 EPA:DHA.
By Dr. William Davis
=================================================================
Read the complete article here.
□ indicates baseline SBP; ▪, postintervention SBP; ○, baseline DBP; •, postintervention DBP; ⋄, baseline HR; and ♦, postintervention HR.
In this group of 56 overweight men with normal starting blood pressures, only DHA reduced systolic BP by 5.8 mmHg, diastolic by 3.3 mmHg.
While each omega-3 fatty acid has important effects, it may be DHA that has an outsized benefit. So how can you get more DHA? Well, this observation from Schuchardt et al is important:
DHA in the triglyceride and phospholipid forms are 3-fold better absorbed, as compared to the ethyl ester form (compared by area-under-the-curve). In other words, fish oil that has been reconstituted to the naturally-occurring triglyceride form (i.e., the form found in fresh fish) provides 3-fold greater blood levels of DHA than the more common ethyl ester form found in most capsules. (The phospholipid form of DHA found in krill is also well-absorbed, but occurs in such small quantities that it is not a practical means of obtaining omega-3 fatty acids, putting aside the astaxanthin issue.)
So if the superior health effects of DHA are desired in a form that is absorbed, the ideal way to do this is either to eat fish or to supplement fish oil in the triglyceride, not ethyl ester, form. The most common and popular forms of fish oil sold are ethyl esters, including Sam’s Club Triple-Strength, Costco, Nature Made, Nature’s Bounty, as well as prescription Lovaza. (That’s right: prescription fish oil, from this and several other perspectives, is an inferior product.)
What sources of triglyceride fish oil with greater DHA content/absorption are available to us? My favorites are, in this order:
Ascenta NutraSea
CEO and founder, Marc St. Onge, is a friend. Having visited his production facility in Nova Scotia, I was impressed with the meticulous methods of preparation. At every step of the way, every effort was made to limit any potential oxidation, including packaging in a vacuum environment. The Ascenta line of triglyceride fish oils are also richer in DHA content. Their NutraSea High DHA liquid, for instance, contains 500 mg EPA and 1000 mg DHA per teaspoon, a 1:2 EPA:DHA ratio, rather than the more typical 3:2 EPA:DHA ratio of ethyl ester forms.
Pharmax (now Seroyal) also has a fine product with a 1.4:1 EPA:DHA ratio.
Nordic Naturals has a fine liquid triglyceride product, though it is 2:1 EPA:DHA.
By Dr. William Davis
=================================================================
Read the complete article here.
Monday, May 20, 2013
Dietary Fats and Health - Lawrence
Dietary Fats and Health
Abstract
Although early studies showed that saturated fat diets with very low levels of PUFAs increase serum cholesterol, whereas other studies showed high serum cholesterol increased the risk of coronary artery disease (CAD), the evidence of dietary saturated fats increasing CAD or causing premature death was weak. Over the years, data revealed that dietary saturated fatty acids (SFAs) are not associated with CAD and other adverse health effects or at worst are weakly associated in some analyses when other contributing factors may be overlooked. Several recent analyses indicate that SFAs, particularly in dairy products and coconut oil, can improve health. The evidence of ω6 polyunsaturated fatty acids (PUFAs) promoting inflammation and augmenting many diseases continues to grow, whereas ω3 PUFAs seem to counter these adverse effects. The replacement of saturated fats in the diet with carbohydrates, especially sugars, has resulted in increased obesity and its associated health complications. Well-established mechanisms have been proposed for the adverse health effects of some alternative or replacement nutrients, such as simple carbohydrates and PUFAs. The focus on dietary manipulation of serum cholesterol may be moot in view of numerous other factors that increase the risk of heart disease. The adverse health effects that have been associated with saturated fats in the past are most likely due to factors other than SFAs, which are discussed here. This review calls for a rational reevaluation of existing dietary recommendations that focus on minimizing dietary SFAs, for which mechanisms for adverse health effects are lacking.
===================================================================Read the complete article from Advances in Nutrition here.
Tuesday, March 5, 2013
Low Levels of Omega-3 Fatty Acids May Cause Memory Problems
Low Levels of Omega-3 Fatty Acids May Cause Memory Problems
Feb. 27, 2012 — A diet lacking in omega-3 fatty acids, nutrients commonly found in fish, may cause your brain to age faster and lose some of its memory and thinking abilities, according to a study published in the February 28, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology. Omega-3 fatty acids include the nutrients called docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).
For the study, 1,575 people with an average age of 67 and free of dementia underwent MRI brain scans. They were also given tests that measured mental function, body mass and the omega-3 fatty acid levels in their red blood cells.
The researchers found that people whose DHA levels were among the bottom 25 percent of the participants had lower brain volume compared to people who had higher DHA levels. Similarly, participants with levels of all omega-3 fatty acids in the bottom 25 percent also scored lower on tests of visual memory and executive function, such as problem solving and multi-tasking and abstract thinking.
The study was supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute and the National Institute on Aging.
Story Source:The above story is reprinted from materials provided by American Academy of Neurology (AAN).
Journal Reference:
- Z. S. Tan, W. S. Harris, A. S. Beiser, R. Au, J. J. Himali, S. Debette, A. Pikula, C. DeCarli, P. A. Wolf, R. S. Vasan, S. J. Robins, S. Seshadri. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology, 2012; 78 (9): 658 DOI: 10.1212/WNL.0b013e318249f6a9
Read the complete article here.
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