Excitotoxins

1. Excitotoxins • What are they? • So what’s the problem? • What’s that have to do with chiropractic?

2. What is an excitotoxin? • These are a group of excitatory amino acids than can cause sensitive neurons to die, when neurons are subjected to excessive amounts of these substances • Glutamine which is converted to glutamate • Glutamate is an excitatory neurotransmitter • Glutamate in excess is a powerful neurotoxin • Monosodium glutamate is the sodium salt of glutamate, and is neurotoxic, used as a flavor enhancer in processed foods • Aspartate is an excitatory neurotransmitter and in excess is a neurotoxin

3. Neurodegenerative diseases • Parkinson’s disease • Alzheimer’s disease • Amyotrophic lateral sclerosis • Huntington’s chorea • Can overstimulation of neurons contribute to the above • Is there a common thread?

4. Other neurologic disorders where overstimulation may play a role • Seizures/epilepsy • Headaches • Brain injury • Strokes

5. Is there a common thread? • Its all a question of balance • To much or not enough create problems • In order to function properly the brain needs a balance of excitatory and inhibitory chemicals/neurotransmitters • Proper stimulation of the brain is one event that is critical to the development and proper wiring of this organ (neural plasticity) • Touch, speech, vision

6. Role of chiropractic intervention • Restore normal joint mechanoreceptor function normalizing afferent input into the spinal cord and brain • May play a key role in optimizing plasticity in the spinal cord and brain • Stimulation of the brain is critical to development and proper wiring • Chronic back pain and atrophy of the brain

7. Out of balance • Overloading the system with excitatory amino acids that are consumed • Flavor enhancers • MSG • Artificial sweetner • “NutraSweet”

8. Miswired brain • Conditions • Cerebral palsy • Epilepsy • Autism • Learning disabilities • Dyslexia • Down’s syndrome • schizophrenia

9. What can cause elevated levels? • What we eat can cause elevated levels in the blood and elevate levels in the brain • Humans concentrate glutamate 20 X higher in their blood compared to monkeys and 5 X higher than mice • Consumption of products containing “NutraSweet”. • Diet soda/pop

10. Sources of MSG • Hydrolysed vegetable protein • Sodium caseinate • Calcium caseinate • Yeast extract • Textured protein • Natural flavoring (frequently contains MSG)

11. “NutraSweet” • Discovered in 1969 by accident by a scientist working with a compound called aspartame as a possible cure for stomach ulcers • A boom to the soft drink business • Aspartame / Nutrasweet Detoxification • Aka Phenylketonurics or phenylalanine • excitotoxic

12. Glutamate receptors • 3 types of glutamate receptors • NMDA, quisqualate, kainate • Activated by both glutamate & aspartate • Glutamate is one the most common neurotransmitters in the brain • Neurons that release glutamate are found in almost all areas of the brain • Cortex, striatum, hippocampus, hypothalamus, thalamus, cerebellum

13. NMDA receptor • N-methy D-aspartate receptor • Most common glutamate receptor • Gates calcium channels • Glutamate/aspartate binding opens calcium channels • Works in concert with other receptors • Zinc receptor activation closes the channel • Magnesium receptor activation closes the channel • Glycine receptor activation necessary for Ca++ channel to open

14. Excitotoxins • Aspartate & Glutamate • Open calcium channels • When these NT are in too high a concentration, the calcium channel gets stuck in open position, allowing too much calcium into the cell • Calcium pumps (E dependent) have to work harder • Cysteine

15. Calcium • Influx of Ca++ activates protein kinase C • Causes more Ca++ release from the ER • Helps keep Ca++ channel open • Excess Ca++ triggers phospholipase C • Causes release of arachidonic acid release from the cell membrane • AA attacked by lipoygenase & cyclo-oxygenase • Inflammatory response mediated by prostaglandins • Promotes formation of free radicals

16. Excitotoxins • Low E levels greatly enhance the toxicity of excitotoxins (glutamate) making you more susceptible to the effects of excitotoxins • Mechanisms that protect the brain from excess excitotoxin accumulation are heavily E dependent • Glutamate pumps that pumps excess glutamate into astrocytes (heavily E dependent) • Magnesium deficiency compounds the problem because Mg++ normally closes calcium channels • Effect released as neuron fires

17. Magnesium • Deficiency in the brain of Alzheimer’s patients • Levels may be low in neurons when plasma levels are normal • Exposure to heavy/toxic metals • Metals compete with Mg++ for entry into brain • Mg++ deficiency can interfere with learning • Hippocampal deficiency in Alzheimer’s • Memory function impaired

18. Aluminum • Affected neurons in Alzheimer’s disease have significantly elevated aluminum levels, and low levels of magnesium • Impairs the function of enzymes that require magnesium • Decrease the formation of acetylcholine • Its toxic effects may be due to magnesium depletion

19. Variation in sensitivity to a toxin • Within individuals of same species • Differences in concentration & competency of protective enzymes • Efficiency of cellular energy production • Differences in absorption from the gut • Between different species

20. Failure of the blood-brain barrier • Trauma • Head injuries • Stroke • Viral infections of brain & spinal cord • Bacterial infections of brain & spinal cord • Hypertension • Heavy metal exposure • Lead & tin • Elevated core body temperature • Aging

21. Areas of the brain without a BBB • circumventricular organs • Area postrema, subfornical organ, laminar terminalis, subcommisural organ, median eminence, posterior pituitary • Consistent with physiological function • Neurosecretory products have to pass across the endothelium into circulation • These areas are especially vulnerable to the effects of elevated levels of excitatory amino acids

22. Glutathione • Antioxidant enzyme (free radical scavenger) • Occurs in two forms • Reduced • Oxidized • By switching from the reduced form to the oxidized form it neutralizes free radicals

23. Domoic Acid/Mussel Madness • Fall of 1987 (Canada) • 3 cases where victims developed disorientation, confusion, memory loss, muscle weakness w/in 24 hours of eating mussels • By December 1987 107 cases reported • 1/3 developed serious neurological symptoms • Mutism, seizures, purposless chewing, grimacing, emotional lability • Those less affected, many had short term memory loss

24. Domoic Acid/Mussel Madness • 4 of 107 died • Microscopic examination revealed a severe loss of glutamate-sensitive neurons in the hippocampus & amygdala • Findings identical to pattern of neural loss when kainic acid (powerful excitotoxin) is administered to animals • Kainic acid binds to non-NMDA glutamate receptors • Source of was from an algae with high concentration of domoic acid that these particular mussels were dinning on

25. Domoic Acid/Mussel Madness • Very resistant to heat • Reacts only with the kainate type of glutamate receptor • 2-3 X more powerful than kainate • 30-100 X more powerful than gluatamate • Can cross the BBB • Subtoxic doses of DA, aspartate, glutamate together can severely damage neurons

26. Cell Membrane • Plays a key role • Receptor function • Ion exchange • Enzyme function • Nutrient entry into the cell • Loss of membrane fluidity with age • Can impair function • Omega 3 fatty acids can improve membrane fluidity

27. Omega 3- fatty acids • Can improve nerve conduction • Are effective in treating bipolar disorder • Caution • Be unsaturated they are subject to rancidity • Keep refrigerated

28. A word about aging • As we age, all cells, including neurons lose a significant amount of their ability to generate energy • Electron transport generate the majority of the cells energy under aerobic conditions • Those electrons are derived from the breakdown of glucose in Kreb’s cycle • Aging is associated with an increase in free radical production along with a decrease in reduced glutathione

29. Free radicals • Highly reactive oxygen species with unpaired electrons in outer shell • Can damage: • cell membranes • Intracellular organelles • DNA • Kept in check by antioxidant enzymes • glutathione, catalase, superoxide dismutase

30. Free radical scavengers • In addition to the antioxidant enzymes (glutathione, catalase, superoxide dismutase) there are a host of scavenging vitamins and minerals • Vitamins • C, E, D, K, beta carotene • Minerals • selenium, magnesium, zinc • Co-enzyme Q10

31. What can be done • Eliminate intake of excitotoxins • Aspartate (NutraSweet) • MSG • Increase dietary intake of organic fresh fruits and vegetables, foods high in antioxidants and omega-3-fatty acids (coldwater fish) • Decreased intake of red meat

32. Excitotoxins The taste that kills Russell L. Blaylock, M.D.