http://www.smart-dru...xcitotoxins.htm
Read all of it. Just by looking at the website, it initially appears that this is just another copy-paste with nothing useful in it. But I gave the article a read and all I can say is WOW. If you've ever wanted to really examine the fundamentals of life extention and neural enhancement, this article in my view is IT.
From reading it I've also re-considered two things:
1. Dropping excess calcium (e.g., HMB supplementation)
Normal levels of calcium inside the neuron allow normal functioning, but when excessive calcium builds up inside neurons, this activates a series of enzymes, including phopholipases, proteases, nitric oxide synthases and endonucleases.(1,3) Excessive intraneuronal calcium can also make it impossible for the neuron to return to its resting state, and instead cause the neuron to "fire" uncontrollably. (1,3) Phospholipase A2 breaks down a portion of the cell membrane and releases arachidonic acid, a fatty acid. Other enzymes then convert arachidonic acid into inflammatory prostaglandins, thromboxanes and leukotrienes, which then damage the cell. (1,3) Phospholipase A2 also promotes the generation of platelet activating factor, which also increases cell calcium influx by stimulating release of more glutamate. (3) And whenever arachidonic acid is converted to prostaglandins, thromboxanes, and leukotrienes, free radicals, including superoxide, peroxide and hydroxyl, are automatically generated as part of the reaction (1-3, 16). Excessive calcium also activates various proteases (protein-digesting enzymes) which can digest various cell proteins, including tubulin, microtubule-proteins, spectrin, and others. (1,3) calcium can also activate nuclear enzymes (endonucleases) that result in chromatin condensation, DNA fragmentation and nuclear breakdown, i.e. apoptosis, or "cell suicide". (3) Excessive calcium also activates nitric oxide synthase which produces nitric oxide. When this nitric oxide reacts with the superoxide radical produced during inflammatory prostaglandin/leukotriene formation, the supertoxic peroxynitrite radical is formed (3,17). Peroxynitrite oxidizes membrane fats, inhibits mitochondrial ATP-producing enzymes, and triggers apoptosis (17). And these are just some of the ways glutamate -NMDA stimulated intracellular calcium excess can damage or kill neurons!
2. Dropping glutamine supplementation entirely!
An enzyme called "glutamate dehydrogenase" also helps neurons dispose of excess glutamate by converting glutamate to alpha-ketoglutarate, a Krebs' cycle fuel. Glutamate dehydrogenase is activated by NADH, so taking the NADH recommended in the energy and antioxidant programs will also promote breakdown of glutamate excess. Excessive levels of free radicals has been shown to inhibit glutamate uptake by astrocytes, the major route for terminating glutamate receptor activation (29), so following the antioxidant program will also aid in clearing excess synaptic glutamate. In order to maximize clearance of synaptic glutamate, it will also be necessary to avoid use of the nutritional supplement glutamine. The health food industry has promoted glutamine use for decades, often in multi-gram quantities. A 1994 book touts glutamine "to strengthen the immune system, improve muscle mass, and heal the digestive tract" (43). It is true that many studies do show benefits form short-term, often high dose, glutamine use. It must be remembered, however, that glutamine easily passes the blood-brain barrier and enters the astrocytes and neurons, where it can be converted to glutamate. And the excitotoxic damage from excess glutamate may take a lifetime to develop to the point of expressing itself as a stroke, Alzheimer’s or Parkinson's disease, etc. But high dose glutamine can cause excitotoxic problems even in the short term. At last year's Monte Carlo Anti-Aging Conference, I met a man who routinely consumed 20 grams of glutamine daily. He suffered extremely severe insomnia, nervousness, anxiety, racing mind, and other symptoms of excessive glutamate neurotransmission. glutamine supplementation should probably not exceed 1-2 grams daily, if it is used at all.
I never even knew that about glutamine. I guess it's like an anti-oxidant in that we all need a certain amount, but too much can be bad for you (in the case of anti-oxidants they have a pro-oxidative effect if you take too much or don't use a full regime of them) but the downside to glutamine it appears is that there is no way to counter the effects of taking above 1g in "extra" supplementation.
Finally, what do you all think of this place? Apparantly it's a store too and they sell QUITE a bit.
http://www.antiaging...m/a2z/home1.htm
They appear to be legit and they have quite a bit of stuff.
Edited by ozone, 22 April 2005 - 09:19 AM.
