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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.

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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.

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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.