POTS and Excitotoxicity
Excitotoxicity in the pathogenesis of POTS, Fibromyalgia, Chronic Fatigue Syndrome, and other disorders
Excitotoxicity is a cause of nerve damage that occurs when neurons become overly excited, begin to malfunction, and sometimes commit cellular suicide. A poignant example of how it occurs is what happens during alcohol withdrawal in persons who are severely addicted. As that person misses a drink, glutamatergic, excitatory neurons which have been suppressed by alcohol for days, months, even years are suddenly switched back on and they become so excited by glutamate/aspartate activation that they influx calcium until they die, leading to in alcohol withdrawals, anxiety and panic attacks, which in the worst cases can progress to delirium tremens with hallucinations, seizures, and even tachycardia so extreme that the heart muscle tears itself and death ensues. This is an extreme example of excitotoxicity.
However, in some conditions such as Parkinson’s and Amyotrophic Lateral Sclerosis, excitotoxicity occurs over an extended period of time, with no known cause. This excitotoxicity affects the motor neurons and sufferers often lose the ability to move efficiently. I believe that in POTS, Fibromyalgia, CFS and other disorders exhibiting autonomic dysfunction, essentially the same process is causative.
In early developing cases of dysautonomia, the causative factors are likely to be largely genetic and having to do with diet. High carb diets with lots of refined sugars and sugary drinks have been shown to have similar effects to drugs like opiates and cocaine on the brain. This effect alone can cause some nervous system problems of which parents are generally aware, calling it a ‘sugar high’. However, the effect gets compounded when refined sugars cause an insulin overshoot which causes vascular dysfunction and hypoglycemia. The body reacts to hypoglycemia by producing more stress neurotransmitters such as adrenaline because they allow quick use of energy in glycogen and fat cells. What this creates in predisposed persons is essentially the same type of excitotoxic damage that occurs in depressant withdrawal but the effect comes entirely from diet. Added to this, an American diet also contains actual stimulants such as caffeine, aspartate from aspartame sweeteners, and glutamate from MSG. If one often experiences ‘the shakes’ from hunger which one seeks relief from sugary foods, then this process of excitotoxicity and depressant dependence is occurring from food the same as it occurs from depressant abuse. The genetics of many persons react this way to diets with refined sugars and fats.
As persons with these sensitivities are treated for mood conditions and other manifestations, the problem can be compounded by any drug that exhibits significant tolerance and withdrawal, including opiates and benzodiazepines. What will happen with these drugs is the same thing that occurs with refined carbs and alcohol, a depressant effect, then rebound excitotoxicity from withdrawal. This effect will often set in partially even if the drug is continued and taken on time each day.
The process can be seen thus, depressants lead to rebound excitation which can cause progressive nerve cell death in motor neurons and other brain cells leading to conditions of dysautonomia as the nervous system is continually over-and-under shooting trying to balance itself. Here are some steps to take to reduce or eliminate excitotoxicity so that healing can occur.
A low insulin diet. This will eliminate hypoglycemic episodes. Ketogenic diets and Atkins diets may work well for those who can tolerate them. For those who need higher carb amounts, choose carbs which have a low glycemic index, which take longer to digest and are hard, solid, and fibrous, rather than white, soft, and sugary. Ketogenic diets i.e. high healthy fats with low or no carbs are used to treat epilepsy and seizures in those who don’t respond to traditional medication so it is already known that this diet will decrease neuron excitability.
- Reduce tolerance and withdrawal from medications. Benzodiazepines and opiates can worsen or cause excitotoxicity as neurons go into withdrawal even if you don’t miss a dose. To reduce this problem, choose medications with less tolerance and withdrawal including medications like Lyrica, gabapentin, buprenorphine, Vistaril, and clonidine for pain and anxiety rather than Xanax and oxycontin which can produce strong dependence and withdrawal. Where stronger medications are needed, be sure to discuss with your doctor methods of decreasing tolerance and withdrawal, which is possible even with the strongest pain and anxiety medications.
- NDMA antagonists. I have found that NDMA antagonists, at sufficient doses, will powerfully block excitotoxicity to improve symptoms from chronic pain and POTS. I have studied doses of dextromethorphan 150 to 300 mgs and found it to control anxiety, depression, chronic pain, and POTS symptoms. These doses are above current prescribing guidelines and are not safe as DXM becomes a dissociative hallucinogen at higher doses such as used in some studies and has significant and potentially dangerous drug interactions. However a lower dose of 90mgs of dextromethorphan has shown efficacy in reducing fibromyalgia pain in several studies. The active ingredient, dextromethorphan is available over the counter in cough medicines. A prescription formula called Nudexta is available for the treatment of pseudobulbar affect in MS, ALS, and Parkinson’s disease.
Ketamine is another NDMA antagonist that has shown promise but it not yet available in the formulation used in studies. Magnesium is the body's natural NDMA antagonist. Choose bioavailable forms of magnesium including magnesium citrate, taurinate, glycinate, sulfate as sources that are bioavailable rather than the magnesium oxide in cheap supplements which cannot be absorbed by the body. Magnesium in bioavailable forms is as potent as prescription anxiolytics and healthier. Magnesium supplementation should be explored before using dextromethorphan or antidepressants since it is natural and potentially more effective or more effective used in conjunction with antidepressants as many studies have demonstrated.
- Anticholinergics. Antimuscinarics are helpful for those with hyperadrenergic symptoms such as sweating and anxiety. I have found OTC doxylamine in Unisom when taken at night with clonidine produces an antimuscanaric anti-pain effect that persists throughout the day.
As a disclaimer, I am not making medications recommendations. Any medications you are interested in, you should research and discuss them with your doctor and let us know if you find significant relief since that information can help others.
I have found potent blockade of NDMA receptors to produce periods of total remission far above the effects of other medications. I have also found a low carb diet with sufficient calories from healthy fats such as medium chain triglycerides and fish oils to produce extraordinary gains against chronic pain and POTS symptoms by reducing excitotoxic blood sugar peaks and crashes. Anticholinergics I have found to help tremendously with sweating, shaking, heat sensitivity, and pain. It is important to find anticholinergics with less potential for tolerance, dependence, and side effects.
I believe, though I have not yet proven, that POTS can be cured by the combination of diet and glutamatergic blockade. I have been able to induce remission but not extinction of POTS and chronic pain and anxiety symptoms with these methods. I believe that once the hypoglycemic process is reversed completely, excitotoxic damage will cease and a curative healing can be ensue.
Thanks for reading. This article is informed by my own study and experience. I understand that other people have different bodies and causes for their symptoms. I’d like to know what you think. Leave a question or comment.
-DF Seldon, MS, NBCC