(this was taken from a post to CFSFMExperimental@yahoogroups.com on 2/28/06)
At the
OHM meeting last weekend, a talk on lipid replacement therapy was presented by
Dr. Rita Ellithorpe of the Tustin Longevity Center in southern California. In
addition, I had extensive discussions with John Casey, President of Nutritional
Therapeutics, the producer of the products NT Factor and Propax. I've also
(both recently and in the past) read some papers that Dr. Garth Nicolson has
written about lipid replacement therapy trials. Based on all of this, I want to
comment on this subject in relation to CFS.
As I think most of you are aware, it has been shown quite conclusively by
several studies that most PWCs are in a state of oxidative stress. It is well
known that glutathione is at the basis of the antioxidant enzyme system in the
body, which normally protects against oxidative stress. We also know that many
PWCs are depleted in glutathione, and that some have genetic defects in some of
the enzymes that use glutathione to prevent oxidative stress. It is my belief
that these problems with the glutathione system are the reason for the state of
oxidative stress in many PWCs.
(By way of review, in order to put things in context, as I've been writing since
the beginning of November, 2005, I believe that there are vicious circle
mechanisms in many PWCs that prevent the glutathione level from coming back up,
and that these result from inherited genetic variations in enzymes that impact
the sulfur metabolism, particularly the methylation cycle, the transsulfuration
pathway, and/or sulfoxidation, and also from the buildup of toxins, particularly
the metals mercury, lead and aluminum, which occurs when glutathione is depleted
for an extended period of time and the person is exposed to these metals in
various ways. I believe that the types of nutritional treatments used by the
DAN! project doctors and by Dr. Amy Yasko are the best way to compensate for
these genetic variations and toxins and to break the vicious circles so that the
glutathione level will be allowed to come back up to normal, and that these
treatments will get to the root cause of the chronic nature of CFS in many PWCs.)
What I want to write about now is the accumulated effects of the long term state
of oxidative stress in CFS, and what can be done about that. What I'm
suggesting is that it is very important to get to the root cause of CFS and to
deal with it, but that it is also important to correct damage that has occurred
during the time the PWC has been in the state of oxidative stress.
As you may know, when cells are in a state of oxidative stress, the reactive
oxygen species (including oxidizing free radicals) react with lipids, proteins
and DNA, particularly in the mitochondria (power plants) of the cells, where
most of the reactive oxygen species are formed as a byproduct of oxidative
metabolism. Without effective antioxidant enzyme system operation, the excess
reactive oxygen species damage these cellular species, and that has deleterious
effects on the operation of the mitochondria, which lowers the energy supply to
the cells. We are getting more evidence lately that there is mitochondrial
dysfunction in CFS, including the ATP Profile testing by John McLaren Howard of
the BioLab Medical Unit in London, the experience of Dr. Sarah Myhill in use of
the supplements pioneered by Dr. Stephen Sinatra for heart conditions, and the
impedance cardiography and echocardiography measurements reported by Dr. Paul
Cheney, showing diastolic cardiomyopathy in CFS, which has its origin in
mitochondrial dysfunction.
It is well established that the lipids, as are found in the inner and outer
mitochondrial phospholipid membranes, bear the brunt of the attack by the
reactive oxygen species. In particular, the unsaturated fatty acids (omega-3
and omega-6) which are an integral part of these phospholipids, sustain most of
the attack, because fatty acids are highly reduced chemically and are the most
chemically reactive of the fatty acids. This has been discussed in papers by
Prof. Martin Pall and by Dr. Kenny de Meirleir and associates, among
others. Several studies have shown that PWCs are particularly depleted in these
essential unsaturated fatty acids, including a recent one by Dr. Maes as well as
several earlier ones. Some studies have shown that PWCs benefit from
supplementing with lipids containing these fatty acids. It is very important to
have sufficient unsaturated fatty acids as part of the phospholipids that form
the membranes in order to maintain the fluidity of the membranes, which is
necessary for proper operation of the protein transporters that carry substances
in and out of the mitochondria, and part of the mitochondrial dysfunction in
PWCs is undoubtedly due to depletion of these fatty acids. These unsaturated
fatty acids are also important for the formation of eicosanoids, such as
prostaglandins, which act as local hormones and exert control on variety of
processes, including inflammation. The flexibility of red blood cells also
depends on unsaturated fatty acids in their membranes, and they need to be
flexible to squeeze through the capillaries, which have smaller inside diameters
than the size of the undistorted red blood cells. You may recall that Dr. Les
Simpson of New Zealand emphasized the supplementation of essential fatty acids
in CFS (ME) for this reason.
However, if a person takes flax oil or fish oil or evening primrose oil, for
examples, the body must convert the unsaturated fatty acids in these supplements
to phospholipids if they are to be used in mitochondrial and other cellular
membranes. If the mitochondria are not in good condition, it is likely that
this process will not proceed at a normal rate. In recent years, various
approaches have been used to attempt to bypass this conversion, which requires
energy and may not be operating efficiently in people who are ill or in older
people. Dr. Patricia Kane and her associates have used intravenous infusion of
phospholipids, together with intravenous glutathione infusions, and have
reported good results. The first liposomal glutathione supplement on the
market, which was Lipoceutical Glutathione, from Wellness Products, makes use of
hydroxylated phospholipids to form the microsomes. Makers of the other two
liposomal glutathione products (Essential GSH from Wellness Health, and LipoFlow
Glutathione from LipoFlow) claim that their phospholipids are unaltered and can
be used by the cells directly. I don't know of direct testing that demonstrates
how well these phospholipids can be incorporated in cells.
In addition to these approaches, there is also a product called
NT Factor, manufactured by Nutritional
Therapeutics, Inc. This product was initially developed to treat leaky gut
syndrome. The idea was to supply unoxidized phospholipids to the cells lining
the gut. Probiotics and prebiotics as well as antioxidant protection were
included to help the delivery of the phospholipids. When the resulting
supplement was tested, it was found that it not only helped the gut, but also
other organs in the body. It appears that excess phospholipids were also
transported to the cells of other organs as a result of the diffusion gradient,
and became incorporated in cell membranes as well as mitochondrial membranes,
improving function. Therefore, this supplement was tested in various groups of
people including people with fatigue (not specifically limited to CFS), older
people, and people under treatment for cancer. Some of these studies were done
by Dr. Garth Nicolson, who you may know was coauthor of the monumental paper
many years ago that set forth the fluid mosaic model of the cell membrane, which
was a major advance in the understanding of membrane structure and function.
Dr. Nicolson is well-positioned in terms of his experience in membrane science,
cancer therapy, and the study of fatiguing illnesses to understand the function
of this product, and I have confidence in him.
The results of this testing and of the clinical experience of the doctors using
NT Factor, including Dr. Rita Ellithorpe, who spoke at the OHM meeting, has been
that this product is very effective in restoring mitochondrial function in these
groups of people, as evaluated by improvement in their fatigue. Lab experiments
on animals also showed that the electrical potential across the mitochondrial
membranes was significantly improved, and this is a measure of their function.
I don't know how NT Factor's benefits compare with those of the other methods
used to do lipid replacement therapy, but it does appear that there is a good
scientific basis for this product, and Dr. Ellithorpe said that in her
experience with trying various approaches on her patients, this was the best she
has found.
I have no financial interest in this product.
Rich