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This page is dedicated to the memory of my father, CDR Paul L. Dennis, USN (Ret.), who battled sideroblastic anemia for nearly seven years. He was a decorated war hero, loving father, devoted husband, and above all else a gentleman. I miss him dearly.
The author of this page is not a medical professional and makes no drug claims for the following information. Although the protocol described contains non-toxic, non-prescription ingredients, and is based on relevant medical research, it also is unproven by established medical science. YOU are responsible for your own health! The author has no vested or monetary interest in anything contained on this page, but believes the information may be able to help those with various anemias and other diseases of the marrow. It is in this spirit that this is presented to you.
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My interest in sideroblastic and aplastic anemia (and related diseases) began when my father was diagnosed with sideroblastic anemia in the mid 1990s. He had been exceptionally healthy for many years until he noticed, at age 69, he was starting to get very short of breath after only moderate exertion. He thought he must have developed heart disease and finally went to the Naval Hospital for an evaluation. The doctors said his heart was fine, but he was very anemic. Tests determined he had sideroblastic anemia. At first the family breathed a sigh of relief, but as we learned more about the disease we felt less assured. We learned it is sometimes referred to as "smoldering leukemia", and like leukemia is a disease of the bone marrow. It is considered an "orphan disease" with comparatively little research currently being undertaken. However it, along with other myelodysplastic and aplastic anemias, is a disease whose frequency is on the rise. Some researchers I have spoken to think exposure to benzene-related compounds is THE culprit, although others disagree.
Even more distressing, we learned that for a person over the age of 55 or so current medical science offers no treatment options with any significant likelihood of working. Care consists of regular transfusions of blood with careful monitoring of blood chemistry, especially iron levels. For younger patients, these diseases are treated aggressively in a similar manner to attacking leukemia i.e. killing off the bone marrow with chemotherapy, followed by a bone marrow transplant.
After learning all of this I became determined to learn more about this disease in the hope of helping my father.
After many many hours of research I have come to believe that there are some key nutrients and supplements needed to help fight these anemias and help ameliorate the damage caused by persistent and profound anemia. Most of the information to follow will focus on a substance called N-Acetylcysteine, or NAC for short. This information is written in a simple writing style so as to not bombard the reader with medical jargon, and because I am not a doctor nor scientist and do not even begin to claim a thorough knowledge of the biochemistry involved. However, the Pubmed abstracts I link to are often filled with technical details. The easiest way to discern what is going on in an abstract is to read the title, go to the bottom and read the conclusion(s), then read the rest of the text.
Current research is showing that myelodysplasia and similar diseases is caused by improper regulation of cellular growth. A substance called TNF-alpha appears to be main culprit. TNF stands for "tumor necrosis factor". It does just what the name says. The body uses TNF-alpha to stop improper cell growth and destroy tumor cells. But in cases of myelodysplasia, the TNF-alpha for some reason kills off the good, developing bone marrow cells before they can mature to the point where they then generate red blood cells and platelets.
This is where N-Acetylcysteine (NAC) comes into the picture. Way down deep at the cellular level, the body produces and uses substances called cytokines. TNF-alpha is a cytokine. These cytokines are basically signalling agents. There are many different kinds. Depending on what their roles are, cytokines either make something start or else make it stop. There are chemical pathways for cytokines in the body that tell TNF-alpha to either start killing off cells or stop killing them off. But in myelodysplasia and related anemias the cytokines do not work correctly. TNF-alpha is turned on at the wrong times. See:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9883804&dopt=Abstract
Anti-cytokine therapy suggested for myelodysplasic syndromes
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8847900&dopt=Abstract
Cytokines and TNF-alpha implicated in myelodysplastic syndromes
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10752992&dopt=Abstract
Elevated TNF-alpha levels noted in patients with myelodysplastic syndromes. Differentiation inhibited
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10052711&dopt=Abstract
Yet again anti-cytokine therapy suggested
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12008086&dopt=Abstract
Higher TNF-alpha levels in MDS
Researchers have found that NAC keeps those cytokine pathways from incorrectly signalling TNF-alpha to kill off the good but still-developing bone marrow cells. On top of that, NAC also ensures that TNF-alpha kills tumor cells when it is needs to. For an analogy, think of TNF-alpha as an old fashioned light switch with two push buttons, the cells as a light bulb, and the NAC as someone pushing the buttons on the light switch. When you want the room dark so you can sleep, you want to be sure the light is turned off. When you want light so you can read a book before snoozing, you want the switch to be pushed to the on position. Inside the body, NAC helps turn on or off these cytokines in an appropriate manner. In the case of sideroblastic anemia, one important role NAC plays is that of an anti-cytokine, thus keeping normal bone marrow cells from being killed off by TNF-alpha. It also helps in the proper signalling of TNF-alpha in destroying defective bone marrow cells that cannot form viable red blood cells or hemoglobin. Typically in these anemias normal marrow cells are eventually crowded out by defective marrow cells to the point where the body no longer produces blood cells capable of carrying oxygen. See:
New! http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12601528&dopt=Abstract
NAC causes a significant decrease in plasma TNF-alpha in the elderly
New! http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12678402&dopt=Abstract
NAC reduces reduces TNF-alpha, reduces reactive oxygen species levels, and increases glutathione peroxidase activity
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11062741&dopt=Abstract
NAC prevents inappropriate cell destruction and inhibits damage from low oxygen states
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9242544&dopt=Abstract
NAC turns off TNF-alpha when it is incorrectly killing off normal cells
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10438532&dopt=Abstract
NAC reduces inappropriate signalling of cytokines
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11301180&dopt=Abstract
NAC regulates cytokines
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11156586&dopt=Abstract
Again, NAC regulates cytokines
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11978899&dopt=Abstract
NAC inhibits TNF-alpha
From the above noted research you can see that NAC is being tested as a therapeutic agent for many ailments, including cancer, leukemia, and heart disease. However, this in vitro study puts it all together:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10654448&dopt=Abstract
NAC reduced TNF-alpha levels in MDS cells. It greatly improved bone marrow cells chance of surviving. When the normal marrow cells are allowed to mature they then produce normal red blood cells and platelets.
Since NAC is an antioxidant, an effective way of raising glutathione levels in the body, and a source of sulfur, it also offers other benefits to great to be considered just fringe benefits:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11896744&dopt=Abstract
Low plasma cysteine levels linked to muscle wasting and immune system dysfunction
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11820776&dopt=Abstract
NAC protects red blood cells from damage
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11691805&dopt=Abstract
NAC protects bone marrow from myelosuppression caused by toxic compounds
In summary, I believe strongly that supplementing with N-acetylcysteine may help sideroblastic and aplastic anemia patients improve their blood profile by assisting in the preservation and development of normal bone marrow cells, and possibly in keeping abnormal cells from reaching maturity. Plus NAC offers other benefits such as protection from muscle wasting and protection of erythrocytes.
**New Information: Additional research is also looking at another cytokine, related to TNF-alpha, called TRAIL (tumor necrosis factor alpha related apoptosis-inducing ligand). Note that once again cysteine (and n-acetylcysteine) play an important role in the proper functioning of TRAIL. See: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11840265&dopt=Abstract and
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10947965&dopt=Abstract
If you decide to try the suggested experimental adjunct treatment protocol, please stay on it for at least one month (preferably two months) in order to give the protocol time to start working. You have nothing to lose.
Before I conclude I must note to you what happened when I convinced my father to try some of these ideas, including the NAC. In early summer of 2001 I purchased for my father NAC tablets, mixed carotenoids, and a B12 sublingual spray. He had for many months been on injections of Epogen® along with his weekly blood transfusions and Desferal® (iron chelator). His blood counts stayed fairly stable but with no improvements. After 4 weeks of taking the NAC, B12, and mixed carotenoids his blood work improved, with a noticeable improved in hemoglobin. However, he stopped taking the NAC as it upset his stomach severely. About a month later his blood levels returned to their previous lower state, despite the continued injections of Epogen®. I attempted to get his physicians to provide for him a prescription for buffered NAC by sending them the information presented on this page and the information for Westlab pharmacy. However they refused to follow up on this information and he, discouraged by the doctors and a skeptic himself despite the experience he had, stopped pursuing the matter. There is much more to be told regarding my father's illness and the attitudes of the Naval hospital physicians but I will not go into detail here.
Please feel free to email me at groovetube66@yahoo.com with any thoughts you may have. I will try to answer your questions but please keep in mind I am not a medical professional. It is a very good idea to inform your physician if you attempt this protocol. This will help to guard against inadvertent duplicative or interfering therapy, and help your doctor to monitor for positive and negative effects. Although I cannot and have no business telling you what to do, it is my strong belief that you should COMBINE this protocol with any current "mainstream" treatments you may be given. The combination of epoetin with NAC should be synergistic. I am hoping the information on this page can help you - myelodysplastic or aplastic anemia patient, caregiver, doctor, researcher, or friend - in battling this terrible disease.
If you decide to try this protocol please contact me with what you have done, what the test results were, and your subjective impressions of any changes in your health. I plan to update this page as more relevant research abstracts are posted on Pubmed.
copyright Sean Dennis 2003-2007
last update, February 8, 2007