see the video: http://vimeo.com/28441817
In February, I did talk about the relationship between stress and inflammation, but one of the problems, especially during times of active detox, that many of the kids encounter is aggression. There is a tie in that goes on with aggression and the stress pathway. So, I’ve been spending a bit of time since February looking at apraxia, and we’ve talked about that a bit today. We’ll talk about it a bit more tomorrow, but also, what we can do to address the aggressive situation that can happen during detox.
So, again, as I usually do, looking at the pathways involved and the processes that are initiated so that we first understand what’s going because it puts us in a better position to address it. There’s a couple of key mediators that are involved in key mediators. Some of them are mediators that I haven’t really talked about too much in the past.
Histamine you’re all probably familiar with because it’s involved in allergic reactions, but many of you may not be familiar with bradykinin or protein kinase C or substance P. So, a number of these, if they’re out of balance, will create problems with aggression. Also, if we have imbalances with dopamine and serotonin, if they get too high, those mediators can feedback and inhibit themselves and drop too low and create aggressive behavior.
Now, there’s a very tight tie in between aggression and pain. So, when you’re feeling pain and extrasensitivity, it leads to problems with aggressive behavior, and we’ll talk about, in a moment, the relationship that’s already been very well characterized between COMT status and pain sensitivity. So, there’s a large recognition that pain and distress are tied together with aggression, and the mediator for that, where it all comes together, is the level of bradykinin in the system.
So, we’ve talked about, in the past, the angiotensin system when we look at ACE mutations. To refresh your memory, going from angiotensin I to angiotensin II, when you have that ACE deletion, it causes and increase conversion of the angiotensin I to angiotensin II, but what we haven’t talked about in the past is the fact that bradykinin is also acted on by that same enzyme, the angiotensin-converting enzyme. So, it will break it down into inactive peptides.
So, while having an ACE deletion that causes this conversion at a higher level causes us some difficulties. Again, the whole them of moderation this weekend because that same ACE deletion will play a role in helping to break down bradykinin, and that means that individuals who do not have an ACE deletion may be in a position to have higher levels of bradykinin. So, aggression may be more of a problem if you have no ACE deletion during times of high detox, especially depending on your COMT status. Those who are COMT++ may be more sensitive to pain. So, if you’re COMT++ and you do not have an ACE deletion, bradykinin may be more of a player in terms of aggressive behavior.
Just to remind you, when we convert angiotensin I to angiotensin II, we get higher levels of aldosterone, and aldosterone competes with cortisol in terms of looking at this stress response. We’ll get into that a bit later. So, we’re looking at two parallel pathways that this particular enzymes can help to break down bradykinin so that we’re less likely to have some of the issues with aggression. Yet, at the same time, we’re making more aldosterone, and that competes with our cortisol and works against us when it comes to the aggression pathway.
Again, looking at bradykinin and protein kinase C, this is a diagram we’ve looked at before in terms of triggering an inflammatory cascade that we can use chamomile for to help to balance, and polyamines which are tied together with SAMe levels will help to tone down protein kinase C. So, if we’re lacking in SAMe or methylation function and we don’t have enough polyamine, the levels of protein kinase C may be higher. Protein kinase C is central in the cascade tied together with bradykinin. It increases the bradykinin receptors. So, it’s going to add to the aggressive pathway, and protein kinase C is also triggered by calcium in this map, 38-kinase inflammatory cascade that I’ve talked about in the past.
Now, remember earlier today, I spoke about the fact that the dopamine-4 receptor is triggered by the MAT enzyme and a methionine at a particular point. Most of the receptors in these membranes are actually interactive with protein kinase C, and so, for instance, inhibitors of protein kinase C eliminate the signs of morphine withdrawal. So, it’s tied together with a mechanism of addiction and withdrawal for drugs.
If we look at prolonging the agony, again, in other words, what prolongs the pain sensation and the pain sensation is tied together with aggression. Some of the mediators in this pathway are protein kinase C and substance P are involved in this pathway. In terms of the COMT status, why some people feel pain and others don’t is related to your COMT status. So, those who are COMT++ will feel more physical pain actually than those who are COMT- -.
Here we go, the blowup I was just talking about. When we’re looking at the pain cascade, we have glutamate again. Every time we turn around, glutamate’s in the middle of what we’re talking about. Protein kinase C, MAT-38 kinase being triggered, substance P. So, all the mediators that we’re looking at now in terms of the aggression pathway.
Again, looking at what happens with pain, certain inflammatory mediators like COX-2 and some of the herbs that we use, the supplements, the RNAs, help us to keep the inflammatory cascade in better balance. Again, the level at which this is being triggered is at an RNA level. So, using certain things like the health foundation, nerve calm, the aggression support helps us to keep this pathway in better balance.
When we have damaged tissues, it creates pain, dilation of blood vessels, bradykinin. That’s related to your mast cells which is where your IgE-mediated immune response comes from and release of histamine. So, this is all tied together with aggression. So, some of the kinds of things that can help us are supplements like quercetin or butterbur which are going to help to stabilize the mast cells so they don’t release as much histamine will help us with aggression. The hyperimmune RNAs and SAMe will help. As I already mentioned, aggression and health foundation, stress and comfort to try to get some edge of that pain and the pain-stimulated aggression response.
Now, high levels of adenosine can be generated via the methylation pathway, and there’s been work to show the in some autistic children, the level of adenosine can be particularly high. That can then act on the mast cells to cause the release of histamine, and histamine, then, is tied into this aggression-bradykinin pathway.
One of the tools that we have besides the butterbur and the quercetin is also to look at the methylation support formula which will help us to stabilize some of the imbalances leading to higher levels of adenosine. Again, adenosine is going to be generated by our methylation cycle so when you get adenosine, we’re going backwards from the histamine. We’re tied together with this whole bradykinin pathway.
The use of the methylation support helps to stabilize us a bit. Also, the new apraxia support formula will help us with that, but both of those do trigger some fairly significant detox. So, you’re in a little bit of a circular issue. If you’re having aggression and you’re trying to stabilize it somewhat, you don’t want to be triggering that much more detox, or you may accelerate the problem. So, just very low levels of something like methylation support and apraxia support not high doses to trigger more detox and aggravate an aggressive situation.
Also, looking at the interaction between adenosine and what goes on with serotonin release, imbalances in the serotonin levels. We like our serotonin levels balanced all the time just like with our dopamine levels. So, adenosine is going to suppress serotonin release, and it’s going to give us some of those imbalances in serotonin that can be related to mood swings as well as aggravating aggression. So, some of the tools we have for that would be low doses of St. John’s wort, Mood S, 5-HTP. The company that makes that new B12 patch is coming up with a patch that looks like it has TNA and 5-HTP in it for a more sustained time release support system for 5-HTP and TNA. That may also be helpful for keeping serotonin levels more balanced as well as help with aggression and mood.
Again, looking at the relationship between serotonin triggering the release of substance P which creates capillary permeability, inflammatory cascades, again bradykinin, and the perception of pain and lower pain threshold for some individuals. So, again, the COMT++ status would create a lower pain threshold. If, on top of that, we’re having imbalances in serotonin, release of substance P and bradykinin, we create a situation where we have some of these non-ideal behaviors.
Using sufficient magnesium besides magnesium to help with balancing calcium levels may help to keep the level of substance P in better balance. So, when we look at the urine essential element test, you’ll see this in some of the case studies I’ll be showing tomorrow, I like the magnesium levels to be the right off 50% whereas the calcium levels to be the left of 50%. Doing what will help us keep the substance P in better balance.
The hydrogen sulfide that we talked about earlier today that’s generated as a result of the CBS upregulations or mutations in SUOX can lead to an increase in norepinephrine as well as serotonin, and that can then play a role in feeding back, inhibiting more serotonin and aggravating this aggression and hyperactivity cycle. Some of the kinds of things we can use in those cases would be attention support, ammonium support if we have CBS or a SUOX mutation as well as some DM and SAMe.
Now, in addition, the hydrogen sulfide has been shown to inhibit MAO, and those are the enzymes that break down serotonin as well as act on dopamine. So, if we have fluxes in the levels of serotonin and dopamine, it’s going to aggravate some of those aggressive behaviors. So, again, looking at ways to try to keep the hydrogen sulfide in better balance, dealing with the CBS mutation, dealing with the SUOX mutation, and using some of the RNAs, Mood D and Mood S, to try to keep things a little more even.
Now, MAO-A is the enzyme that breaks down serotonin, and so, looking at that in particular, CBS upregulations are going to increase sulfide levels. That, then, plays a role in affecting MAO-A. We have MAO-A mutations that we look at. Many of the kids are MAO-A++.
Stress and Aggression,