Post by beebs on May 30, 2011 18:23:24 GMT -5
Copied & Posted my own post from FAVC -
This is for educational purpose only: Do your own research specially the latest concerning Omega 3, can be harmful for many. Hum, best to read and self monitor rather than just popping pills. Remember, individual responses and so on.
We cannot separate since all systems are connected. Reading up on ROS, Mito, NO, NMDA receptors etc... puts in perspective how very complex it is. It all weaves in nicely, that is the little we know and for contradictions ;D, and constant evolving theories,
Dr Pall's NO-ONOO theory: 74.6.238.254/search/srpcache?ei=UTF-8&p=dr+palls+theory+NO+ONOO&xa=FZwze2tAFvT99CkqIhJaBQ--%2C1306883937&fr=moz35&u=http://cc.bingj.com/cache.aspx?q=dr+palls+theory+NO+ONOO&d=4750152426193702&mkt=en-US&setlang=en-US&w=5f954796,e8aa81d&icp=1&.intl=us&sig=6gW03iLpolRj3Hro4gncMg--
Summary/Excerpts from Dr Pall's theory about his
vits and supps protocols:
There are 23 distinct agents/classes of agents found in these products that are predicted to down-regulate the NO/ONOO- cycle biochemistry. Most of these predictions are discussed and documented in Chapter 15 of my book “Explaining
‘Unexplained Illnesses’”. All 23 of these are described in the following Table 1:
Table 1
Agent or class Mechanism Comments
Vitamin C (ascorbic acid)* Chain breaking antioxidant; lowers NF-kappa B activity; reported to scavenge peroxynitrite and also help restore tetrahydrobiopterin
(BH4) levels May require high doses to be effective with the latter two mechanisms; this may be the basis of so called “megadose therapy” for vitamin C Vitamin E including tocopherols and tocotrienols Lipid soluble antioxidant;
gamma-tocopherol may be particularly useful in scavenging breakdown products of peroxynitrite; tocotrienols may be particularly important in protecting from excitotoxicity and protecting mitochondria; lowers NF-kappa B activity High dose alpha-tocopherol, the most commonly used form of vitamin E induces an enzyme that degrades other forms of vitamin E; thus high dose alpha-tocopherol should be avoided, in my view Magnesium* Lowers NMDA activity and may be useful in improving energy metabolism
and ATP utilization Magnesium is the agent that is most widely studied and found to be useful in the treatment of the multisystem illnesses N-acetyl cysteine (NAC) Precursor in the synthesis of reduced glutathione.
Some people with multisystem illnesses appear to be sensitive to this, possibly because of excitoxicity of the cysteine produced from it; we use a relatively modest dose here and suggest always taking it with meals Fish oil (long chain omega-3 fatty acids)* Lowers iNOS induction; important for brain function; alsolowers production of inflammatory protaglandins Highly susceptible to lipid peroxidation and may, therefore be depleted Flavonoids* Chain breaking antioxidants; some scavenge peroxynitrite, some scavenge superoxide; some reported to induce SOD; All three types are found in FlaviNox; some flavonoids may also act to help restore BH4 levels; lower NF-kappa B activity Flavonoids go up rapidly in the blood after consumption but also drop rapidly; taking them four times a day is an attempt to maintain higher blood levels over much of the day Carotenoids, including beta-carotene, lycopene, lutein.
These are all reported to scavenge peroxynitrite in lipids, such as biological membranes Only natural forms are used here; the natural form of beta-carotene has substantial amounts of cis double bonds, whereas synthetic beta-carotene is predominantly all trans and largely inactive as a scavenger; the other carotenoids are very active, particularly in certain regions of the body and may be more active than even natural beta-carotene Selenium in the form of seleno-methionine Serves as a precursor for selenoproteins including three forms of the antioxidant enzyme glutathione peroxidase and a selenoprotein reported to be a peroxynitrite scavenger Peroxynitrite reacts with many selenium compounds; if this generates products that are not retained in the body this will lead to lowered selenium levels which have been found in the multisystem illnesses.
Acetyl L-carnitine* Helps transport fatty acids into mitochondria; may be important here not only directly for energy metabolism but also to restore the oxidized fatty acid residues that may be produced by superoxide in the cardiolipin of the inner membrane May also help lower reductive stress Ecklonia cava extract* Polyphenolic chain breaking antioxidant; reported to help scavenge both peroxynitrite and superoxide; based on its reported properties, it may also help restore BH4 levels Appears to stay in the body much longer than do the flavonoids, a useful property; reported to be helpful in a clinical trial study of fibromyalgia Vitamin B6 including pyridoxal phosphate
Multiple functions; is present here primarily because of its activity in the enzyme glutamate decarboxylase (it can be rate-limiting) May help restore balance between glutamate and GABA; lower excitotoxicity and excessive NMDA activity Hydroxocobala-min form of vitamin B-12* Potent nitric oxide scavenger, lowers nitric oxide levels Taking this orally four times per day is an attempt to saturate the intrinsic factor mediated uptake over much of the day and thus get maximum oral uptake; still higher levels can be obtained by injection, inhalation or nasal spray Folic acid* Relatively high doses will lower the partial uncoupling of the nitric oxide synthases by helping to restore tetrahydrobiopterin Reacts with oxidants and therefore may be depleted due to the NO/ONOO- cycle Niacin Helps restore NAD/NADH pools that can be depleted by peroxynitrite mediated poly ADP-ribosylation
This may be important, in turn for lowering
mitochondrial/energy metabolism dysfunction
Riboflavin including 5’-phosphate Multifunctional; main rationale for including it here is to stimulate glutathione reductase, a key enzyme for maintaining levels of reduced glutathione.
One of four agents here that are important for maintaining reduced glutathione; reacts with oxidants and therefore may be depleted due to the NO/ONOO- cycle Thiamine (vitamin B1) Important in energy metabolism, including two steps in pentose phosphate shunt which generates NADPH Critical for NADPH which can act to regenerate reduced glutathione; reacts with oxidants and therefore may be depleted due to the NO/ONOO- cycle R-Alpha-lipoic acid Important antioxidant; helps restore reduced glutathione levels; lowers NF-kappa B activity Rapidly converted in the body to reduced lipoic acid and lipoamide, the most active forms; possibly one of the most
important agents but not tested in clinical trials for multisystem illnesses.
Other B vitamins Biotin reported to be depleted with alpha-lipoic acid supplementation; pantothenic acid important for energy metabolism Coenzyme A (produced from panthothenic acid) is a thiol compound which may be depleted under conditions of oxidative stress; this may be still another mechanism producing energy metabolism dysfunction ethyl glycine (betaine) Lowers reductive stress; also helps with the generation of S-adenosyl methionine (SAM) While the main rationale for including
this here is from the reductive stress concern, SAM generation may also be of concern; the enzyme methionine synthase is inhibited by nitric oxide and inactivated under conditions of oxidative stress, thus leading to lowered SAM
and lowered methylation Coenzyme Q10 (ubiquinone) Important in mitochondrial function; important
antioxidant; reported to scavenge peroxynitrite Optimal dosage may vary considerably among different individuals; suggest taking in the morning as some report it can keep them up at night Zinc, copper and manganese These minerals are all precursors of the antixodant enzyme superoxide dismutase (SOD) and can be rate limiting for its synthesis
under some circumstances Dosage here is important as too high doses can all cause problems RNA (another member of this group has been tested in a clinical trial) Two important functions: Provides adenosine for restoring adenine nucleotide pools after energy metabolism dysfunction; when meatabolized, the purine bases generate uric acid, a peroxynitrite scavenger Two other agents can act similarly:
D-ribose and inosine. Each of the three have their isadvantages, however.
D-ribose is a potent glycating agent. Inosine acts to stimulate mast cells. And the commercial source of RNA is yeast and this may be a problem in those who have a yeast allergy.
Taurine Lowers excitotoxicity including NMDA activity; helps restore balance between glutamate and GABA activity Reported to be depleted in multisystem illnesses
It can be seen from the above-described combination of Allergy Research Group nutritional supplements supply nutrients that help down-regulate various aspects of the NO/ONOO- cycle. Many act as antioxidants, lowering oxidative stress, blocking oxidative chain reactions, and in some cases scavenging such oxidants as peroxynitrite and superoxide or acting to increase superoxide dysmutase
activity. Some agents act to help restore tetrahydrobiopterin (BH4) levels and thus lower partial uncoupling of the nitric oxide synthases. Some agents lower nitric oxide levels.
Some agents act in various ways to restore metabolism. Some act to lower excitotoxicity including excessive NMDA activity.
Some act to lower certain inflammatory aspects including lowering NF-kappa B activity or lowering inflammatory prostaglandin synthesis. Thus all of the various aspects of the NO/ONOO- cycle mechanism as I have proposed it should be
lowered to at least a certain extent.
The theory concerning the biochemistry of the nitrous oxide following chemical injury has its merits. Followers of the Pall Protocol as with the Yasko Protocol seem to improve, the success rate estimated at over 80%. Neither are quick fixes. It takes a few months to a year for sustainable improvement.
See the hypothesis by Dr M Pall, Biomolecular Science, University State of Washington. These protocols should be followed under the supervision of a medical doctor or doctor of biomolecular medicine. Contact details of three biomolecular scientists will be posted under the Good doctors threads, and details of their protocols. These have a high success rate, (unfortunately, not everyone responds). They are mostly nutritional approaches, and some supps need presciptions.
His nutritional protocol. Please note as in previous posts that I have advised against glutamine, which can cause a rise in glutamate, which is excitory, in particular, those with severe CNS symptoms. In fact, quite a few amino acids are known to have these effects, with wiser doctors acknowledging that affects of amino acids are not conclusive.
1. #75930 CoQ-Gamma E with Tocotrienols & Carotenoids: one capsule per day in the morning. Those with body weights over 100 lbs should add a second capsule at mid-day.
2. #75780 FlaviNox: one capsule, four times per day, three preferably with or after meals. Those with body weights over 120 lbs, should add a second capsule with each of three meals.
3. #75940 MVM-A Antioxidant Protocol, multivitamin mineral supplement with added N-acetyl carnitine: one capsule, four times per day, three preferably with or after meals. Those with body weights over 120 lbs, should add a second capsule, with breakfast and with dinner.
4. #75960 NAC Enhanced Antioxidant Formula: one each twice per day, with or after breakfast and supper.
5. #71250 & #73870 Super EPA (fish oil): one per day in the morning after breakfast. Those with body weights over 100 lbs, should add a second capsule at mid-day, taken with or after lunch.
6. #75910 FibroBoost (Ecklonia cava extract): one each twice per day, with or after breakfast and supper.
7. #70010 Buffered Vitamin C: one capsule, four times per day, preferably three with or after meals.
I am suggesting that the three products that are to be taken four times per day, be taken at the same times, with three being taken with or after the three meals of the day and the fourth taken at bedtime.
I suggest that for those intending to try all seven, that you start with the first, trying it alone for three days to see if it is well tolerated, adding second for three days, and so forth. By doing this you should find if there are any products that are not well tolerated, such that they can be eliminated for the time being and perhaps be tested later with either the same or possibly lower dosage. It will take 21 days, in this way, to get to the end of the initial period, into a period where all tolerated products are being taken.