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http://www.healthlink.com.au/nat_lib/htm-data/htm-supp/supps41.htm Lipids and Derivatives The 1980s can be called the decade of fat (lipid) consciousness several prestigious medical and scientific organizations decided that there is ample evidence that a high-fat and high-cholesterol diet is not healthy and that it is time that people lowered fat and cholesterol intakes. In 1988 the U.S, Surgeon General joined this battle, making it a top health priority. Actually, not all lipids are our enemies; as youll soon learn, some are looking downright friendly. Lipids are a heterogeneous group of biologic compounds that in contrast to carbohydrates and proteins are defined according to their solubility rather than their chemical structure. Of all the biologic substances, the lipids are those that are least soluble in water. Lipids are commonly called fats, although in stricter usage fat comprises the most abundant kinds of lipids called triglycerides or neutral fats. In addition to triglycerides, substances classified as lipids include phospholipids, (phosphatidylcholine, phosphatidyle thanolamine, phosphatidylserine and phosphatidy Inositol (Myo inositol) and Phosphatidylinositol, cholesterol, steroids (cortisone, testosterone, estrogen, progesterone), sphingolipids ( Glycosphingolipids , sphingomyelin and cerebrosides), fatty acids (saturated, mono unsaturated, polyunsaturated prostaglandins and leukotrienes) and vitamins A, D, E and K. High cholesterol levels are associated with an increased incidence of coronary heart disease and heart attacks. Diets of Western societies have had a tendency to be high in triglyceride (common fats), cholesterol and fatty acids, especially of the saturated types. We now know that increased intake of fatty acids of the mono unsaturated types (eg, oleic acid found in olive oil) and of the polyunsaturated types (linoleic acid, can lower serum cholesterol levels and protect against coronary heart disease. Recently some evidence has emerged that even one of the saturated fatty acids, stearic acid, can lower serum cholesterol levels. Long-chain fatty acids, found in cold-water oily fish, can decrease platelet stickiness, which is also considered beneficial in the prevention of coronary heart disease. The so-called fish oils can lower cholesterol levels in those who also have elevated triglyceride levels and they also have anti-inflammatory properties. Linoleic acid, which is an omega-6 polyunsaturated fatty acid, was considered, until recently, the only essential fatty acid for humans. That is, humans cannot make linoleic acid and are thus absolutely dependent on dietary sources for it. The omega-3 fatty acid, alpha-linolenic acid, which is found in certain plants, is now also considered essential. An important concept that has now become popular is that of membrane fluidity. This refers to the responsiveness and resiliency of cells. As cells age, their membranes become less fluid and more rigid. The ratio of cholesterol to phospholipids (mainly phosphatidylcholine) in the cell membrane is associated with its fluidity. The higher the ratio the lower the fluidity and vice versa. Also, the greater the degree of saturation of fatty acids in the membrane structure, the less its fluidity. By the same token, the greater the degree of unsaturation of fatty acid, the greater its fluidity. Cellular membrane fluidity can be influenced by diet. Nutrients that increase membrane fluidity include fish oils and phosphatidylcholine (of the type that contain polyunsaturated fatty acids). Diets low in saturated fats and cholesterol maintain membrane fluidity; diets high in these substances produce rigid membranes. Thus, we see that cholesterol not only plugs up our arteries but also our very cells. A new field is emerging called membrane engineering. Substances are now available, made from lipids, which can fluidize cell membranes and potentially rejuvenate cells. Fats may, ironically, turn out to be some of the most exciting anti-aging, disease-fighting nutritional and pharmaological substances of the next decade. http://www.healthlink.com.au/nat_lib/htm-data/htm-supp/supps43.htm PHOSPHATIDYLSERINE AND PHOSPHATIDYLETHAN Phosphatidylserine and phosphatidylethanolamine are phospho Lipids and Derivatives present in the structure of cell membranes. (phosphatidylcholine, as discussed earlier, is the major phospholipid found in human cell membranes). A 1987 report by an Italian scientist showed that when phosphatidylserine was given orally to rats with known age- dependent declines in cerebral function it improved memory deficits, prevented the decline in learning capacity observed in aged rats, restored age dependent electroencephalogram (EEG) abnormalities and prevented some degenerative nerve cell changes in certain parts of the brain. Other reports show similar behavioral benefits in animals, and there are reports that phosphatidylserine can activate cells of the immune system. Phosphatidylserine is thought to work by stimulating repair of cell membranes. Preliminary results of a multi-center trial in Italy on phosphatidylserine in Alzheimers disease patients have now been reported It appears that after the first six months of the study, improvements in memory and overall decrease in dementia were observed, but only in the most severely demented patients. Phosphatidylserine does not appear to have any adverse side effects. Future results of this study are eagerly awaited and will, perhaps, be confirmed by others. Capsules containing phosphatidylcholine, phosphatidylethanola-mine and phosphatidylserine are available in Europe and are use for the enhancement of memory. There are only anecdotes regarding their benefits. Finally, it should be noted, phosphatidylethanolamine is part of the structure of AL 721. http://www.healthlink.com.au/nat_lib/htm-data/htm-supp/supps40.htm AL 721 In late 1986 reports began circulating in the popular press and in some medical magazines about a substance that was being used in Israel for the treatment of ARC (AIDS-related complex) and AIDS. The substance is called AL 721. In most cases, letters and/or numbers are code terms for experimental medicines to hide their true identities. This was not the case for AL 721. AL 721 stands for active lipid made up of 70 percent or 7 parts of neutral lipids, 20 percent or 2 parts of phosphatidylcholine and 10 percent or 1 part of phosphatidylethanolamine. The lipids are derived from egg yolk, which means that their fatty acids are mainly of the saturated variety. AL 721 exists as an aggregate of the above lipids, a kind of soap bubble, if you will. It is thought to work by modifying the structure and fluidity of cell membranes by removing cholesterol and possibly adding phosphatidylcholine and phosphatidylethan olamine to the membranes. Membrane fluidity, which is crucial to the cells responsiveness and processing of nutrients and information, is determined by the ratio of cholesterol and phospholipid (mainly phosphatidylcholine), or the C/PL ratio of the membrane. The greater the C/PL ratio, the more rigid or less fluid the membrane, and vice versa. Typically the C/PL ratio increases with aging and this is associated with certain cells, such as immune cells, losing their special functions. AL 721 was developed by the Israeli scientist Meier Schinitzky and colleagues at the Weizmann Institute in 1981, and was shown to lower the C/PL ratios of several different types of cells, even though its phosphatidylcholine utilizes saturated fatty acids. Its reported benefits, if confirmed, seem to hinge on its unusual geometry. Many pathogenic human viruses contain lipid membranes as part of their structure. Such viruses include herpes simplex I and II, herpes zoster, cytomegalovirus (CMV), Epstein-Barr virus (EBV), the influenza viruses and HIV (human immunodeficienay virus), which is the prime player in AIDS. In November, 1985, a letter appeared in the New England Journal of Medicine demonstrating AL 721 clearly interfered with the infection of cells by HIV in vitro (in the test tube). Presumably, it did this by altering the lipid membrane of the virus. Others have reported that AL 721 interferes with the infectivity of herpes virus in animals, as well. In 1986 it was reported that several AIDS patients who were being treated with AL 721 in Israel appeared to do better clinically. Since the method of making AL 721 was published and the patent readily obtainable, it wasnt too long before copycat or work-alike versions of AL 721 became available in the United States. In fact, the company that holds the patent on AL 721 decided against pursuing FDA approval of the substance as a drug and instead, at this writing, plans to sell it as a food supplement. AL 721 or, more commonly, one of the AL 721 work-alikes have been, or are being, used by many who are infected with the HIV virus including those with lymphadenopathy syndrome (LAS), ARC and AIDS. Those who use these substances usually start with 10 grams twice a day for a month and then 10 grams daily. Some report feeling better when taking this substance, some report improvement in their T-helper Iymphocyte counts (these cells decrease as the disease progresses), some report no difference and some say they do worse. But, overall, those taking these substances appear to be doing better clinically than before they started taking them. No one, however, believes AL 721 is a cure for AIDS. There are a few studies going on looking at the effects of AL 721, in LAS, ARC and AIDS patients, either alone or in combination with the anti-viral agent AZT. A 1988 study looked at the effects of AL 721 in eight patients with LAS. AL 721 given at 10 grams twice daily was found to reduce the extent of HIV proliferation in five of the patients and to improve immune-cell responsiveness in four of the patients. No change was noted in the number of T-helper lymphocytes AL 721 was stopped after eight weeks and then restarted after a four-month period at 15 grams twice daily. The results were not nearly as positive in the follow-up study, a rebound effect had earlier been reported, suggesting that those starting the substance should continue it without interruption. It is possible that AL 721 will play a useful role, even if a small one, in the fight against AIDS. In addition, AL 721 may have immune-enhancing effects. The Israeli scientists withdrew Iymphocytes from men between seventy and seventy-five years old and found that treatment of these cells in vitro (in the test tube) with AL 721 produced a marked increase in immune responsiveness. In another experiment, blood taken from elderly subjects was found to have significantly greater anti-bacterial activity if the subjects were first treated with AL 721. AL 721 did not stimulate lymphocyte activity of young subjects, nor did it increase anti-bacterial activity of blood from young donors. Immune responsiveness is known to decrease with age, and the Israeli researchers believe that AL 721 has a rejuvenating effect on the immune system of the elderly. Much more research is needed to verify this. It is possible that whatever benefits this substance may have in HlV-infected individuals are due to immune enhancement, though AL 721 may also have direct anti-viral activity. The Israeli researchers found that AL 721, given orally or by injection, reduced, or almost completely eliminated, withdrawal symptoms in morphine-addicted mice. More research on the possible role of AL 721 and phosphatidylcholine in the treatment of drug addiction is urgently needed. AL 721 has also been suggested for the treatment of Chronic Fatigue Syndrome, which appears to be increasingly prevalent these days. In some cases of chronic fatigue, viruses as well as immune dysfunction's are involved. Some with these disorders are trying AL 721 at doses of 10 grams daily or 10 grams twice a day, and in a few cases those who are taking it claim that it makes them feel less tired. These are all anecdotal reports. There have not been any controlled studies on the effects of AL 721 in this illness. Reversal of aging of cells, rejuvenating the immune system, anti-viral activity, abolishing the withdrawal symptoms of drug and alcohol dependence, and more; such are the claims for AL 721. Will it turn out to he a miracle substance or will it fizzle out as many have before? Only time and continued research will tell the story. It is apparent, however, that various lipids look very promising as potential therapies in a wide range of ailments. Perhaps Al. 721, even if it doesnt live up to its promises, will help point the way to new lipid preparations that will.