There is no universally agreed upon staging system, so healthcare providers may use the one that they are most familiar with.
Multiagent protocols lowering several aspects of the cycle appear to be the most promising approaches to therapy.
These include an entirely over-the-counter nutritional support protocol developed by the author in conjunction with the Allergy Research Group. This paper argues that what is called the central couplet of the cycle, the reciprocal relation between peroxynitrite elevation and BH4 depletion, is not being adequately downregulated by these multiagent protocols.
It is suggested, then, that treatments that simultaneously effectively downregulate both ends to the central couplet, when used along with multiagent protocols lowering other aspects of the cycle and avoidance of stressors that otherwise upregulate the cycle, will lead to substantial numbers of cures of these chronic diseases.
It is that various short-term stressors can initiate this cycle which, like all vicious cycles, propagates itself over time.
The cycle then, depending on where it is located in the body, causes various chronic diseases. And that is where things becomes much more complex. Each of the arrows shown represents one or more mechanisms by which one element of the cycle raises the levels of another cycle element.
There are now a total of 30 specific mechanisms involved here, most of which are well-documented, well-accepted biochemistry and physiology. Peroxynitrite, a potent oxidant, produces oxidative stress lower center, Figure 1. On the right side of Figure 1 are a number of inflammatory responses, including elevation of the transcription factor NF-kappa B, increased production of inflammatory cytokines upper right box and also induction of the inducible nitric oxide synthase iNOS.
Nitric oxide synthase activity may be elevated not only from iNOS induction but also from the calcium-dependent elevation of the other two nitric oxide synthases, nNOS and eNOS upper center. Multiple mechanisms lead to increases in superoxide center left both intramitochondrial and extramitochondrial.
And mitochondrial dysfunction leads to lowered energy metabolism and depletion of ATP, the energy currency of the cell lower left. Another important cycle element is the elevated activity of the NMDA receptors which leads, in turn to what has been called excitotoxicity Figure 1, top.
Peroxynitrite oxidizes BH4 at physiologically relevant concentrations leading to a BH4 depletion. In partial uncoupling, this superoxide can react in turn with the nitric oxide produced by adjacent coupled enzymes, leading to more peroxynitrite.
Because the reaction between superoxide and nitric oxide is extraordinarily rapid, what is called diffusion controlled, the production of both molecules by adjacent enzymes may be particularly effective in raising peroxynitrite levels.
It should be noted that the production of superoxide remote from the production of nitric oxide will be much less effective in raising peroxynitrite levels because there are high amounts of superoxide dismutase in cells and extracellular fluid, which destroys most of the superoxide before it travels very far from its site of synthesis.
The importance of this reciprocal relationship between peroxynitrite elevation and BH4 depletion, what we are calling the central couplet, has also been proposed by Foxton et al. There are a total of 17 distinct short-term stressors that are reported to initiate cases of one or more of these diseases, and all 17 are known to be able to stimulate cycle elements, and known or presumed to in turn increase subsequent nitric oxide and peroxynitrite.
The various cycle elements have been found to be elevated in the chronic phase of illness in at least one and in most cases all four of these diseases. Several aspects of the cycle are implicated by genetic studies of susceptibility. Published trial on D-ribose; trial currently in progress suggesting inosine can be helpful.
IV high dose, buffered ascorbate Lowers both ends of central couplet see below ; may be particularly helpful agent. Discussed in detail below.
May also improve brain function. Specifically, agents that lower oxidative stress, lower peroxynitrite, improve mitochondrial function, lower NMDA activity, increase BH4 availability, or have anti-inflammatory activity all appear to be helpful in treatment.
Multiagent Protocols and the Allergy Research Group Nutritional Support Protocol I described the responses to five multiagent protocols developed by different researchers, one of which I had a role in developing, in Chapter 15 in my book.
Each of these apparently produces substantial improvements in many patients suffering from these multisystem diseases, although four of the five have only been tested on one disease.
This nutritional support protocol is described elsewhere as well as on a page of my website thetenthparadigm.
It should be noted, however, that the extent of improvement tends to vary considerably, from responses described as miraculous to modest improvements.
Patients with high levels of mercury in their bodies may react negatively to the protocol, presumably because mercury can be mobilized by the alpha-lipoic acid found in the protocol. One group who appear not to respond substantially, either positively or negatively, are the chronic Lyme disease patients.
I must point out to the reader that I do have a conflict of interest here. I receive a small royalty from the Allergy Research Group for designing much of this nutritional support protocol.
She found, surprisingly for such a small group, statistically significant improvement in physical health measures within four weeks, with a further statistically significant improvement over another four weeks personal communication; statistical analysis performed using a paired Student's t test.
In summarizing the last two sections of this article, there are four important points to be made: Third, and not surprisingly, treatment protocols using multiple agents predicted to downregulate the cycle seem to be more effective than single agents.
Clearly, these four points are very important and exciting, considering that the conventional wisdom has been that there is little that can be done to treat these illnesses.
My own view is that the Allergy Research Group nutritional support protocol is the most promising of these multiagent protocols, because it is relatively inexpensive; it is available over the counter in the US, Canada, and much of Europe; and it apparently achieves good responses despite the limitations inherent in over-the-counter approaches.
However, based on published and to the extent I have access to it unpublished evidence, none of these protocols produces any substantial numbers of cures.
Why has this not happened? My own view, is that the central couplet is insufficiently downregulated in these protocols. The main argument explored in this article is that by more effectively lowering this central couplet mechanism, we may be able to extend these multiple agent protocols to obtain substantial numbers of cures.Glyphosate, the active ingredient in Roundup®, is the most popular herbicide used worldwide.
The industry asserts it is minimally toxic to humans, but here we argue otherwise. Residues are found in the main foods of the Western diet, comprised primarily of sugar, corn, soy and wheat.
Glyphosate's inhibition of cytochrome P (CYP) enzymes is an overlooked component of its toxicity to mammals. Get the latest health news, diet & fitness information, medical research, health care trends and health issues that affect you and your family on ashio-midori.com The subject of aluminium and Alzheimer's disease has been plagued with controversy.
This controversy has served to obscure much of the scientific research in this field, and subseq read full description.
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