Guest guest Posted June 7, 2005 Report Share Posted June 7, 2005 CLA - Conjugated Linoleic Acid - Conjugated or Compromised? • Summary Article • Expanded Version • Full Length 6-part Document with Scientific References: Index, 1, 2, 3, 4, 5, 6, 7, 8, 9 PART 1: Abbreviations Used in this Article http://www.udoerasmus.com/articles/udo/cla1.htm CLA: conjugated linoleic acid, a trans- fatty acid made from the n-6 essential linoleic acid by bacterial or industrial " partial hydrogenation " , or by high-temperature industrial processing. CLA, made by a " bond shift " and a " twist " of the molecule, is *not* a " nutrient " that is ‘essential’ for health. EFA: essential fatty acid, one of two fatty acids (n-6 and n-3) that are ‘essential’ to the body, which means that: The body cannot make them; It must have them for health to be possible; and The body must therefore obtain ‘essential’ fatty acids from foods or supplements. In addition to the 2 EFAs, 20 minerals, 13 vitamins, and 8 amino acids from proteins are also ‘essential’ for health by the above definition. N-6: omega-6, the name by which all members of one family of essential fatty acids is identified. The members include linoleic acid (LA), gamma-linolenic acid (GLA), dihomogamma-linolenic acid (DGLA), and arachidonic acid (AA). LA: linoleic acid, the n-6 essential fatty acid, from which the body makes several derivatives with important functions, including GLA, DGLA, and AA. DGLA and AA are the starting points for making hormone-like Series 1 and Series 2 eicosanoids (formerly called ‘series 1 and series 2 prostaglandins’). AA is also required for the development and function of the brain. N-3: omega-3, the name by which all members of the other family of essential fatty acids is identified. The members of the n-3 family include alpha-linolenic or ALA or LNA), stearidonic acid (SDA), eicosapentenoic acid (EPA), and docosahexaenoic acid (DHA). ALA: alpha-linolenic acid, the n-3 essential fatty acid, from which the body makes several derivatives with important functions, including SDA, EPA, and DHA. EPA is the starting point for making hormone-like Series 3 eicosanoids (formerly called ‘series 3 prostaglandins’). DHA is required for brain development and brain function. -- Introduction CLA has attracted a lot of attention over the past few years, some through the media, but far more through health and fitness magazines. Many claims for benefits have been made for CLA, from weight loss, to antioxidant, anti-cancer and, more recently, to diabetes and cardiovascular disease as well. Is CLA all it’s been cracked up to be? This article addresses that question. Research Studies Of 139 references pulled off the Internet in June of 2001, 29 were published in 2001; 65 in 2000; 33 in 1999; and 15 in 1998. Of these 139 references, the following is a breakdown of topics: 10 were production-oriented studies. 6 were reviews, (i.e., these are not studies). 14 were studies about how to get CLA into different foods. One of these came to the brilliant conclusion that cows eating grass (their natural food) contained a better fatty acid (n3: n-6) profile and more CLA than cows fed concentrates from bags. Wow! What a stunning discovery!1 2 were molecular studies. 24 were studies using cell cultures. 69 were studies performed on animals. 14 studies were carried out on humans. Of these research studies, those carried out in living animals and humans (in vivo) are more likely than studies carried out in various normal and abnormal animal and human tissue cultures (in vitro studies) to show how CLA actually affects human health and disease. And, it is important to note that, while CLA is being touted for many human problems, there are relatively few human studies to draw on. Unfortunately, a substantial number of these studies indicate that CLA does not do in human studies what it appears to do in animal studies. -- Conjugated linoleic acid (CLA) is a mixture of 8 (and perhaps even more) different forms (or isomers)2 of an 18-carbon fatty acid made by a high-heat industrial process from linoleic acid (LA), the omega-6 (n-6) essential fatty acid (EFA). In nature, this is accomplished by bacteria in the stomach of ungulates: beef, goats, sheep and other cud-chewing animals (which include deer, moose, caribou, elk, buffalo, yak, musk ox), and CLA is found in meat and milk fat of these species. Each of its eight different isomers has a different spatial structure and each therefore has different action in the body, with different effects on health. The isomer found in dairy products is mainly the (delta)9c,11t-18:2 isomer.3 Butter normally contains about 5mg of CLA per gram of fat, but this can be increased to 40mg per gram by feeding cows sunflower oil.4 Milk chocolate contained 0.3mg of CLA per gram chocolate in a study.5 Commercially, CLA is made by a high-temperature (overheating) process, or by " hydrogenation " of *soybean* or *canola* oils, or by transformation carried out by bacteria in one of the four stomachs of cud-chewing animals from the n-6 EFA, LA. How is LA Changed to CLA? CLA is made from LA, the n-6 EFA, by flipping one of the double bonds in the LA molecule one carbon closer to the other one. This changes the ‘methylene-interrupted’ double bonds present in EFAs (double bonds start 3 carbons apart) into ‘conjugated’ double bonds (double bonds start 2 carbons apart). At the same time, one of the double bonds found in the cis- configuration in an EFA (hydrogen atoms on the carbons involved in the double bond are on the same side of the molecule) twists 180°. The hydrogen atoms are now in a more stable, but biologically less desirable trans- configuration (hydrogen atoms on the carbons involved in the double bond are on opposite sides of the molecule). Trans- means ‘across’. Hence the name trans- fatty acid. Is CLA an Essential Nutrient? CLA is not an essential nutrient. It is, like monounsaturated (n-9) and saturated fatty acids, a non-essential fatty acid. It is not required for human health. This means that, unlike the n-6 and n-3 EFAs, which we cannot live without, we can live on a CLA-free diet a whole life time and continue to be healthy. CLA is also a " trans- fatty " acid (transfat). To be fair, the 9c,11t-18:2 (the letter " t " after the number " 11 " in this designation means: " trans " ) isomer of CLA found in milk fat and beef appears to be one of the more easily digested trans- fatty acids, and is therefore less toxic than the types of trans- fatty acids found in margarine, shortening, and partially hydrogenated vegetable oils. However, CLA " interferes " with the *conversion* of EFAs (especially n-6) to " derivatives " from which the body makes " eicosanoid (prostaglandin) hormones " . This should concern low fat dieters, who already get too little n-6 EFA, LA. It should also concern those who use flax oil exclusively, because they get too much n-3 in " comparison " to their intake of n-6, and CLA will make their low n-6 status even worse. Conjugated Double Bonds Conjugated double bond systems have antioxidant activity, and some studies suggest that CLA can perform antioxidant functions. Other studies suggest that CLA " increases oxidation " , which is not so good. However, there are hundreds of molecules with antioxidant activity equal to or better than that of CLA. Among those that, like CLA, are oil-soluble there are vitamin A, carotene, vitamin E, and many complex molecules with aromatic carbon rings. Molecules with " antioxidant activity' provide " protection " against degeneration, and hence might have anti-cancer, anti-inflammatory, anti-diabetic, and cardio-protective properties. However, hundreds of molecules from nature provide equal or better protection against degeneration. For instance, about *half* of all " edible green " plants contain anti-cancer, cardio-protective, anti-diabetic, anti-inflammatory ingredients—hundreds of different ones— and they confer their protection in many different ways. Some people in the marketplace suggest that CLA is protective against degenerative conditions, but here too, the research is contradictory, and CLA may be over-rated. In the following pages, I summarized 43 clinical studies done with CLA. The remaining studies came to similar conclusions, or were of a technical nature. I have tried to report fairly. Check out the studies, and judge for yourself. -- PART 4: The negative changes induced by CLA include: Alteration of egg yolk and egg white pH, distribution of minerals in yolk and white, and decrease egg quality and hatchability of chicks;31 At 2% of food, CLA " accelerates " the " decomposition " of storage lipids, resulting in " lipid peroxidation " and " morphological change " in the liver;32 In hens, 2.5% CLA reduced level of n-6 and increased level of n-3 fatty acids;33 At 1% of feed in mice, CLA increased TNFa (tumor necrosis factor alpha, an inflammatory factor) by 12 times, and uncoupling protein UCP-2 (a thermogenic factor) by 6 times; there was liver swelling, increased insulin resistance, a nd leptin depletion;34 Given 1g of CLA every second day, chicks showed altered fat metabolism;35 Given to rats at 3 to 5%, CLA changes the membrane lipids, increasing some and decreasing others, increases antioxidant enzymes in liver, and reduces both LDL and HDL (good) cholesterol;36 At 6.6g/kg (0.66%) of food, CLA increased liver weight by increasing cell size (hypertrophy) but not fat levels in hamsters;37 In rats given 180mg/day of mixed isomers, CLA was found to compete for enzymes used to elongate and desaturate EFAs, thereby " decreasing " the " production " of " EFA " derivatives " important " to health;38 At 10g/kg (1%), CLA " reduced rate " of " bone formation " in rats, while EFAs enhanced bone growth;39 In mice fed an atherogenic diet containing 5g/kg (0.5%) of CLA, CLA " increased " the " development " of " fatty streaks " , one of the atherogenic (heart attack) markers;40 At 3% of food, CLA was ineffective in mice tumor multiplicity , whereas SDA and EPA decreased TM by 50%;41 -- In summary, while CLA has shown promises of improving degenerative condition in animal studies, the promises come with contradictory findings and warnings of worsening of some conditions. -- 3.9g/day of CLA for 63 days *did not* show benefits regarding the prevention of atherosclerosis; blood cholesterol and lipoprotein levels did not change;42 3.9g/day of CLA for 63 days did not show benefits regarding blood coagulation and platelet function;43 Increasing CLA in the fetus correlated with decreased length of gestation;44 3.9g/day of CLA for 63 days did not show benefits regarding immune function in human females;45 4.2g/day of CLA " increased " lipid peroxidation in men with abdominal obesity after one month of use;46 In patients with chronic renal failure, CLA did not help;47 At 3 g/day, CLA resulted in no fat loss, no change in appetite, no change in blood glucose, but increased insulin and produced a transient decrease in leptin; CLA did not affect these parameters in a manner that promotes fat loss;48 At 3 g/day, CLA provided no change in body composition, energy expenditure, fat oxidation, or respiratory exchange ratio;49 4.2 g/day of CLA increased lipid peroxidation, apparently by both enzymatic and non-enzymatic processes;50 3.4 g/day of CLA reduced body fat mass; more than 3.4 g/day did not provide any additional benefit;51 16 g/day of n-6 LA from safflower oil did not result in any increase in CLA in the body, i.e. the human body does not make CLA from LA; -- PART 6: Dose and Effectiveness Taken together, what do these studies say about the health value and future of CLA? It seems that CLA is highly " over-rated " in terms of its human health benefits. More sizzle than steak, as the saying goes. There are several kinds of possibly serious negative side effects from the use of CLA that should not be ignored. These negative effects are found mainly in animals, and accompany the use of doses substantially higher than those used in humans. At the doses used in humans, the research results are quite disappointing. Most human studies find " no benefits " in the " degenerative conditions " for which CLA is recommended: weight loss, immune function, cardiovascular problems, and antioxidant functions. The usual doses of CLA used in animals greatly exceed those used in human studies. T his may explain why animal studies come up with better results than human studies, and my also explain the negative effects of CLA on liver and insulin in rats, and the changes in yolk quality and hatchability in eggs. So there appears to be a dose-related shadow side to CLA. Remove the shadow by lowering the dose, and the benefits also disappear. -- If the Results are Mediocre, what " Drives " CLA promotion? What drives CLA promation is obviously profit. Cheap sunflower oil can be sold at retail for about $150 per pound. In comparison, a pound of Udo's Choice Oil Blend™, which contains about 75% undamaged EFAs (50% n-3), retails for about $20. Natural Sources of CLA: Cream, nature’s richest natural source of CLA, contains 5mg/gram (0.5%) of fat. The dairy isomer of CLA is mostly c9,t11-18:2. That much is apparently safe and desirable for calves. That much CLA in butter is probably safe for humans as well. At 0.5% CLA, a tablespoon (14 grams) of butter provides about 70mg of CLA. To get 3 grams of CLA from butter, one would need to eat more than 40 tablespoons of it, which is 560 grams of 1.25 pounds of butter. That’s a lot more than can be recommended, even if EFA intake is optimal (about 1 tablespoon/body weight in winter; less in summer), the level that makes skin soft and velvety (more in winter, less in summer). By the way, 560 grams of butter is 560 x 0.8 (butter is 20% water) x 9 (calories per gram) = 4,032 calories. Butter, nature’s richest source of CLA, does not provide any creature with very much of it. This may explain why high levels result in disturbing negative (side) effects. In commercial preparations, the c9, t11- isomer is found mixed with large amounts of the t10, c12-18:2 (the letter " t " before the number " 10 " means: " trans " ) isomer, along with smaller amounts of the other six CLA isomers. Each of these has different properties and will therefore have different effects on cell and tissue biochemistry. The specific effects of all isomers are not yet known, but need to be known before safe recommendations for this new mixture of CLA isomers is recommended for health. Commercial preparations also differ from one another in the relative amounts of the different isomers they contain. According to tests that have been carried out, they even differ from batch to batch. Therefore research done on one commercial CLA preparation cannot be automatically transferred to another. This point, conveniently overlooked by manufacturers, is unknown to most consumers. To effectively treat human diseases, for which CLA showed benefits in animals, larger doses would be needed. Instead of 3 grams/day, on which we based out calculations above, and which is already very high when compared to what butter (the richest natural source) could supply, CLA doses would need to be even higher. -- PART 7: How high would these doses need to be? Let’s do some calculations. A man eats about 2.8kg of food daily; a woman eats about 1.7kg. If the diet was normal, it would provide about 55% of calories from carbohydrates, 30% from fat, and 15% from protein (the exact numbers are not critical for this calculation). The food eaten might provide around 2,800 calories for a man, and 1,700 for a woman (I use these numbers just to keep the math easy; the actual number of calories would be lower for a sedentary person, and higher for an athlete, logger, or body builder). To make human food intake comparable to the dry food compositions fed to rats, mice, and other animals in captivity, we have to convert the amount of food eaten by humans into a ‘dry’ (still containing 5-10% water) animal food weight equivalent. If 2.8kg (2,800 grams) provides 2,800 calories about 55% of calories come from carbohydrates at 4 calories per gram, which make up 2,800x0.55/4=385 grams of the food; 30% of calories come from fats at 9 calories per gram, which make up 2,800x0.3/9=93 grams of the food; fat makes up 30% of calories, but only 13% of food weight; 15% of calories come from protein at 4 calories per gram, which make up 2,800x0.15/4=105 grams of the food; 5% of dry weight (600 grams) comes from minerals, which =30 grams of the food; about 5% of the ‘dry’ animal (and equivalent human) food is water, which =30 grams of the food; and 10% of dry weight comes from fiber, which =60 grams of the food. The human equivalent of the ‘dry’ animal food sums up to 703 grams. Of the 2,800 grams of food eaten by a man each day, about 75% (2,100 grams) is water. Based on these figures: CLA at 0.5% of food intake would be 3.5 grams/day for a man, and 2.1 grams for a woman. CLA at 1% would be 7 grams/day for men and 4.2 grams for women. CLA at 2% would be 14 and 8.4 grams for men and women, respectively. 3% CLA would be 21 and 12.6 grams for men and women, respectively. 5% CLA, the highest dose used in studies on animals, would be 35 and 21 grams for men and women, respectively. This would be 2.5 tablespoons for men, and 1.5 tablespoons for women. The high doses of CLA are unaffordable for many, making it impossible in practice to provide effective doses to those who have the problems that CLA might address. Inability to afford the expense may be a beneficial deterrent, given the negative effects associated with higher doses of CLA in animals. At these high CLA doses, negative effects such as those seen in some animal studies would likely occur in humans as well. Remarkably, daily intakes in the 5% of food or even higher (up to 10 tablespoons per day) are appropriate for the more important and at the same time more affordable n-3 and n-6 EFA mixtures. CLA at high doses competes with EFAs and crowds them and their derivatives out of enzyme spaces. This is cause for great concern. The body has no requirement for CLA. But it has an " absolute " *requirement* for EFAs, which should not be interfered with. -- PART 8: What Should be our Focus? Recall that EFAs cannot be made by the body, must be present for the normal (healthy) functioning of every cell, tissue, gland, and organ, and must therefore be provided by foods. Since EFAs are easily destroyed by light, oxygen, and heat, oils containing them should be made and stored under protection from these destructive influences, and should not be used for high heat applications in the home. While they can be used in hot soup or on steamed vegetables, they should not be fried, deep-fried, or even sautéed. They can be used in all kinds of foods—cold, warm, and boiling water-hot foods. EFAs come in two varieties: n-3 and n-6. Both are essential. Both are sensitive to destruction. N-3 is too low for good health in most people’s diet. Low and no fat diets are too low in n-3 and n-6. N-6 is too low in people who use flax oil exclusively as the source of EFAs in their diet (these are primarily people who have been misled, by research on the benefits of n-3s and problems caused by n-6s, to seek to remove n-6s from their diet. It is important to obtain both EFAs in the most beneficial ratio, which we find to be 2 n-3s to each n-6. It is also important that our EFAs come from oils that retain their ‘minor ingredients’, which include antioxidants, phytosterols, lecithin, and other oil-soluble molecules present in seeds and nuts. These ‘minor ingredients’ have major health benefits. When colorless, odorless, tasteless, shelf-stable oils are made, the ‘minor ingredients’ are removed from oils for the sake of longer shelf life. In addition, some of the fatty acid molecules present in the oil are changed from natural to toxic. The toxicity blamed on n-6 oils like corn and safflower results primarily from the removal of ‘minor ingredients’, damage to fatty acids due to careless processing, and lack of sufficient n-3. -- Summary and Recommendations: Bottom Line Instead of using CLA, we need in our diet EFAs made with health in mind, in an optimal n-3: n-6 ratio, " pressed " from " organically grown " seeds, and retaining their natural antioxidants, phytosterols, and other ‘minor ingredients’. Being far less expensive than CLA, such oils can be taken in the 30 to 150 gram/day range over the long term, and confer all of the health benefits hyped for but not delivered by CLA. We recommend this approach as part of the ‘The Right Fat Diet®’, a food program emphasizes green vegetables, the right fat rich in both EFAs in the right ratio and made, packaged, stored and used right (carefully with health in mind), and proteins as the foundation for good health. To make sure that digestion works effectively, we recommend that digestive enzymes be taken with meals. The Right Fat Diet® lowers most cardiovascular risk factors, provides the EFAs essential for insulin function, inhibits fat production and enhances fat burning, promotes healthy fat loss, increases thermogenesis, and improves insulin sensitivity. The Right Fat Diet® also improves brain function and mood, inhibits cancer, enhances bone mineral retention, improves protein retention, has anti-catabolic benefits, improves skin beauty, increases energy, stamina, performance, recovery, and healing of injuries, and improves thyroid, adrenal, and reproductive gland functions. Further, The Right Fat Diet® decreases inflammation, improves digestion, reduces allergy symptoms, and decreases the problems of autoimmune conditions. Finally, The Right Fat Diet® enhances food flavors, suppresses appetite, and improves the absorption from food of oil-soluble phytonutrients with health benefits. All of the benefits touted for CLA (and more) are more effectively provided by good old EFAs. That’s why we use the following slogan: -- " Forget CLA, and remember EFA. " -- References - click link for article or abstract French P et al. Fatty acid composition, including conjugated linoleic acid, of intramuscular fat from steers offered grazed grass, grass silage, or concentrate-based diets. J Anim Sci 2000 Nov; 78(11): 2849-55. Eulitz K et al. Preparation, separation, and confirmation of the eight geometrical cis/trans conjugated linoleic acid isomers 8,10- through 11,13-18:2. Lipids 1999 Aug; 34(: 873-7. Ma DW et al. Conjugated linoleic acid in Canadian dairy and beef products. J Agric Food Chem 1999 May; 47(5): 1956-60. Bauman DE et al. Technical note: production of butter with enhanced conjugated linoleic acid for use in biomedical studies with animal models. J Dairy Sci 2000 Nov; 83(11): 2422-5. Hurst WJ et al. 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Tsuboyama-Kasaoka N et al. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetics 2000 Sep; 49(9): 1543-42. Latour MA et al. Effects of conjugated linoleic acid. 1. Fatty acid modification of yolks and neonatal fatty acid metabolism. Poult Sci 2000 Jun; 79(6): 817-21. Stangl GL. High dietary levels of a conjugated linoleic acid mixture alter hepatic glycerophopholipid class profile and cholesterol-carrying serum lipoproteins of rats. J Nutr Biochem 2000 Apr 1; 11(4): 184-91. de Deckere EA et al. Effects of conjugated linoleic acid (CLA) isomers on lipid levels and peroxisome proliferation in the hamster. Br J Nutr 1999 Oct; 82(4): 309-17. Sebodio JL et al. Geometry of conjugated bonds of CLA isomers in a commercial mixture and their hepatic 20:4 metabolites. Lipids 1999 Dec; 34(12): 1319-25. Li Y et al. Dietary conjugated linoleic acid alter serum IGF_1 and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids. J Bone Miner Res 1999 Jul; 14(7): 1153062. Munday JS et al. Dietary conjugated linoleic acids promote fatty streak formation in the C57BL/6 mouse atherosclerosis model. Br J Nutr 1999 Mar; 81(3): 251-5. Petrik MB et al. Highly unsaturated )n-3) fatty acids, but not alpha-linolenic, conjugated linoleic, or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice. J Nutr 2000 Oct; 130(10): 1434-43. Benito P et al. The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 2001 Mar; 36(3): 229-36. Benito P et al. The effect of conjugated linoleic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 2001 Mar; 36(3): 221-7. Elias SL, Innis SM. Infant plasma trans, n-6, and n-3 fatty acids and conjugated linoleic acids are related to maternal plasma fatty acids, length of gestation, and birth weight and length. Am J Clin Nutr 2001 Apr; 73(4): 807-14. Kelly DS et al. Dietary conjugated linoleic acid did not alter immune status in young healthy women. Lipids 2000 Oct; 35(10): 1065071. Basu S et al. Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity. Clin Sci (Colch) 2000 Dec; 99(6): 511-6. Lucchi L et al. Changes in conjugated linoleic acid and its metabolites in patients with chronic renal failure. Kidney Int 2000 Oct; 58(4): 1695-702. Medina EA et al. Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Lipids 2000 Jul; 35(7): 783-8. Zambell KI et al. Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Lipids 2000 Jul; 35(7): 777-82. Basu S et al. Conjugated linoleic acid induces lipid peroxidation in humans. FEBS Lett 2000 Feb 18; 468(1): 33-6. Blankson H et al. Conjugated linoleic acid reduces body fat in overweight and obese humans. J Nutr 2000 Dec; 1301(12): 2943-8. Herbel BK et al. Safflower oil consumption does not increase plasma conjugated linoleic acid in humans. Am J Clin Nutr 1998 Feb; 67(2): 332-7. _________________ _________________ JoAnn Guest mrsjoguest DietaryTipsForHBP www.geocities.com/mrsjoguest/Genes AIM Barleygreen " Wisdom of the Past, Food of the Future " http://www.geocities.com/mrsjoguest/Diets.html Discover Have fun online with music videos, cool games, IM & more. Check it out! Quote Link to comment Share on other sites More sharing options...
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