Dave Johnson's Proletariat Protocol
Source for this document is a discussion thread on the ALSTDI forum, where also updates will be posted.
- 1 Introduction
- 2 The Proletariat Protocol - Dave J. version
- 3 The Pile of Pills
- 4 Candidates for Addition to the List
- 5 Nutritional supplements, herbs, and OTC's rejected for Proletariat Protocol:
- 6 Prescription Drugs That Might Be Worth Taking
- 7 Prescription drugs and related OTC's etc. to avoid in ALS
- 8 Other Protocols Worthy of Mentioning Here
- 9 REFERENCES AND RESOURCES
- 10 Short Essay: ALS Fads
- 11 Short essay: What does "neuroprotective" mean?
- 12 NEXT PILE OF PILLS
- 12.1 CONTENTS OF THE PILE
- 12.2 PILE OF PILLS: DISCUSSION
- 12.2.1 First, the boilerplate
- 12.2.2 Introduction
- 12.2.3 Stuff to begin with
- 12.2.4 If all that goes fine for several days, then:
- 12.2.5 If that goes well for two days, then introduce the following, one at a time every two days:
- 12.2.6 Items that may provide quick symptomatic improvement, and possibly long term benefit:
- 13 What’s most important?
- 14 Summary, grouped by therapeutic action
A protocol (in this context) is a system of medical treatment. For the purpose of treating ALS, numerous protocols have been proposed, and some have resulted in credible reports of benefit for some patients. This is the ALSTDI "ALS Research & Treatments" forum: therefore we don't believe in "untreatable". ALS is treatable, and the question is which treatments are most likely to produce benefit.
Of reported therapeutic successes, most have come from patients who knew how to do medical research and who had money to spend doing their own thing. My own story is like that. Unfortunately the average ALS patient does not know how to do medical research and doesn't have much money to spend on therapeutics. (Insurance won't pay for ALS therapeutics, it's cash out of pocket.) Furthermore the average ALS patient does not have a medical doctor who knows anything about ALS therapeutics; or if the doctor does, the doctor will not apply that knowledge to help the patient.
The Proletariat Protocol is aimed at patients in the USA who are newly diagnosed and are trying to get started on a therapeutic protocol as fast as possible without having to spend a lot of money or to depend on their medical doctor for advice. This particular version is my (Dave Johnson) version. ....... Other "ALS Yodas" are invited to publish their own versions, keeping in mind what a "Proletariat Protocol" is and is not. Proletariat Protocols are not a replacement for other protocols which are based on other criteria or are intended to target specific therapeutic concerns.
BOILERPLATE: This is not "professional medical advice", that's what your neurologist is for. (Good luck on that one!) These statements have not been evaluated by the FDA. For general information purposes only. Offer void where taxed or prohibited. Subject to change without notice. Your mileage may vary.
WHAT IS "ALS"? If you've been diagnosed with "ALS", you have amyotrophy, but nobody knows whether or not you have lateral sclerosis. And you do have upper motor neuron disease even though the phrase "ALS" doesn't indicate that. When you read or hear "ALS", it's best to mentally substitute the international phrase "Motor Neuron Disease" which is more scientific, and which also tacitly admits that we're referring to a syndrome. We're not making assumptions regarding the cause of the observed disease condition or the biological processes which underlie it. As it turns out, MND is marked by diversity of clinical signs and symptoms, diversity of causes, diversity of biological processes, and diversity of outcomes. What's not diverse is the neurologist's proposed therapeutic regime: "Sorry chap, the Merck salesman was just here an hour ago and they still ain't got anything. Could I interest you in a clinical trial?"
As a newly diagnosed ALS patient, you probably don't know what caused you to get ALS. The field of ALS genetics and disease marker discovery is making progress in these areas, but what the scientists may do 5 years from now is no help for you today. When it comes to treating ALS, you're on your own. Sorry, that's the current state of the art. Treating ALS is a do-it-yourself project. Fortunately, when it comes to DIY ALS therapeutics, this very forum is the best place on the entire planet. When I say "best", I mean that nothing else is even in second place. This is where the action is.
So, how good is the Proletariat Protocol compared to anything else? Heckuva good question, and unfortunately no straight answer is possible. Here's my best stab at it.
- Let's begin with what the Proletariat Protocol is and isn't. It is a cocktail approach based on readily available inexpensive ingredients. It is fairly general, not making very much distinction between different types of ALS. It does not address the issues of hypermetabolism & muscle wasting, which deserve their own additional protocol, presumably ketogenic diet. And, inasmuch as it does not include any therapeutic strategy knowingly targeted to genetic defects in glia/astrocytes, the Proletariat Protocol will probably not do very much for patients having such genetic defects (for example fALS mSOD1).
- Sorry to sound so pessimistic. On the upside, most patients who have credible reports of major therapeutic benefit, were doing a protocol of this same general nature. It's that track record of occasional success with cocktail therapies that led to the Proletariat Protocol.
- What makes this particular Protocol different from all the others, is that this one was developed in plain view right here in the ALSTDI Research & Treatments Forum, with critique by some of the smartest ALS researchers on the entire planet. Although Dave J. is the guy actually doing this project, it has been and continues to be a project with quite a bit of PALS and research community involvement. It's got peer review.
- The Proletariat Protocol is not driven by commercial considerations. I'm not selling any ALS-related products or jockeying for a job with a biotech company. That having been said, Life Extension Foundation was an early leader in the field of do-it-yourself ALS cocktail therapeutics and I've been trying to drag them back into it. Sorry to report that so far my invitation has gotten no traction.
The Proletariat Protocol - Dave J. version
The components of the Protocol comprise three major categories:
- Lifestyle do's and don'ts.
- "Pills" (actually, mostly capsules) which may provide immediate symptomatic improvement. Most of these may also slow disease progression, but their potential to provide immediate results makes them of special interest.
- "Pills" the purpose of which is to slow disease progression. It will probably take weeks or months (rule of thumb: 3 months) to know if they're helping, and since you'll be doing a pile of them, you won't know of the pills in the pile which ones are actually helping and which ones are a waste of money.
The long list of things which could have been included as components of the Protocol has been weeded down to just a few things according to the following preferences.
- It's gotta be cheap and available in the USA without assistance from a medical doctor. (This is a fundamental criterion for inclusion.)
- There has to be a body of science suggesting its probable usefulness.
- It has to be nearly without downside risk.
- I have relied heavily on credible reports of efficacy coming from persons who post on this forum. To me, one credible anecdotal report of efficacy is worth more than a hundred PubMeds. A lot of PubMed is absolute crap, and even the reported results of clinical trials should be subjected to ruthless critique. (We're good at that here.)
- Therapeutic components (usually "pills") that may produce immediate (within hours or several days) symptomatic improvement are to be preferred over those which lack such potential. You can find out in a hurry what actually works for you and what doesn't.
- Therapeutic components which are not aimed specifically at symptom improvement but rather at slowing disease progression, should have a pretty solid basis in the scientific literature. "Solid basis" in this context does not necessarily mean a long history or a huge number of publications, it's more about the quality of the basis.
- A lot of what we think we know about the biology of ALS comes from research on one specific "mouse model", 93a. ALS is many diseases and nobody reading this is a mouse. Nonetheless I regard good quality mousework as superior to in vitro labwork, and regard claims of extension of life after disease onset exceeding delta 15 days as worthy of serious attention.
- There is abundant evidence in both humans and in animal models that the ALS disease process is typically that of a "neurodegenerative cascade". The biological processes prior to symptom onset are those of homeostasis (keeping things in balance, even though something may be out of whack), whereas after symptom onset the body's attempt to maintain things in balance has failed and the body's attempt to clean up the resulting mess inadvertently winds up causing further damage to motor neurons. Therefore, a therapeutic regime, in order to be maximally effective, has to tackle a wide range of processes in an attempt to stop the neurodegenerative cascade and to enable the body to recover homeostasis. In practice, this means an effective protocol needs to be a pile of various components, it's not likely that any one "pill" is going to suffice to correct the problem.
Lifestyle Do's and Don'ts
- Exercise as you are able, but do not exercise to the point of extreme fatigue. http://blogs.als.net/post/Exercise-does-a-body-good-But-what-about-pALS.aspx Moderate exercise helps keep active the body's repair processes. But for someone with ALS, pushing beyond that into lactic acidosis is pushing into a regime that the body has lost the ability to compensate. .......The single most common anecdote among newbies is "a year ago I was running marathons, and now I can't walk without crutches, what happened?" That's not the most common anecdote you hear among heart attack or lung cancer victims. ALS is different from the customary couch potato degenerative diseases.
- Get plenty of sleep. In order to survive ALS your body's repair mechanisms have to be allowed to function, and most repair happens during sleep. http://ens-newswire.com/2013/10/18/brain-cleans-itself-of-toxins-during-sleep/
- If you're under a lot of stress, and if there's some way you can get out from under that stress, do it. Prolonged stress impairs your body's ability to repair itself.
- Regarding Vitamin A (including retinoids) supplementation, there is conflicting information. Natural dietary carotenes aren't a problem.
- Don't supplement with copper, and avoid foods high in copper such as shellfish. Don't use copper or brass cookware. (More on this subject later.)
- Don't supplement with iron, unless prescribed by a medical doctor for treatment of anemia.
- Don't supplement with "pills" that claim to increase SOD-1. Since wild-type (normal) SOD-1 can become misfolded (and therefore toxic)in sporadic ALS, such supplements are likely to make the disease worse.
- Don't go berserk piling on antioxidant supplements, choose antioxidants carefully. A lot of patients have tried flooding their bodies with all kinds of antioxidants (out of desperation, not knowing what else to do), and that approach has a dismal track record of failure. There are theoretical reasons to believe that overdoing the antioxidants may even throw your body's ability to control oxidation out of whack leading to accelerated disease progression. Do however make sure you have adequate vitamin C intake.
- Don't drink aspartame sweetened soft drinks. Most bodies are strong enough to handle that neurotoxin but yours may not be.http://www.als.net/forum/yaf_postsm387065_Glutamate-esp-biological-regulation-thereof.aspx#387065
- Don't eat foods that are high in free glutamate flavor enhancers such as MSG, soy sauce, hydrolyzed vegetable protein, yeast extract, or aged cheeses such as Parmesan. Most bodies are strong enough to handle a sudden excess of glutamate but yours may not be. http://www.als.net/forum/yaf_postsm387065_Glutamate-esp-biological-regulation-thereof.aspx#387065
- Avoid aluminum compounds. This means aluminum-based antiperspirants, alum as an additive to pickles, aluminum-based antacids, and the use of aluminum cookware where the food being cooked comes into contact with an aluminum surface.
- If you are taking statin drugs, either stop or begin supplementing with plenty of CoQ10. If your medical doctor argues with you, tell the cuss that ALS patients don't die from heart attacks, you want high cholesterol to protect what's left of your nervous system. It should provoke an interesting conversation......... You need to find out NOW what your doctor does and doesn't know, and what conversations are and aren't possible. ALS therapeutics are a DIY project and the question is not who can do it for you, the question is who can provide useful support on that very personal journey.
- If you're taking phytosterol nutritional supplements (esp. saw palmetto), stop taking them. Beta sitosterol does have certain health benefits, but over time it compromises brain health by substituting for cholesterol.
Whatever you do or don't do, first read up on it sufficiently that you at least know what it is and have some idea how it works. You don't have to become an expert on the stuff but you don't want to be popping pills without even knowing what they are. Wikipedia is usually the best place to start. In nearly every case there will be lots of info here, too, but plowing through the posts can be time-consuming and tedious.
The Pile of Pills
- Dexthromethorphan (DM). Over-the-counter cough suppressant, usually in the form of cough syrup. There are several kinds. Read the label carefully (get the pharmacist to help you if necessary). Get something that has only DM as the active ingredient, no antihistamines or decongestants or expectorants. Then take the stuff at twice the label recommended dosage for two days. There's a good chance it will help with bulbar and/or upper motor neuron symptoms. (You know what those are, right? If not, you need to revisit ALS 101.) Probably won't help with lower motor neuron symptoms. If you see improvements in symptoms, keep it up, but cut dosing back to the label recommendation. If at any time you notice mental side effects, reduce dosage or stop entirely. Long term use of DM probably reduces the rate of disease progression when combined with other cocktail ingredients: the mere fact of being a Ca++ channel inhibitor suggests this, see also http://www.als.net/forum/yaf_postst52536_SigR1.aspx .
WARNING: if you are taking any prescription antidepressants, before taking DM you need to read up on Serotonin Syndrome inasmuch as combining DM with prescription antidepressants can lead to that syndrome: other potentially problematic substances include diphenhydramine (Benadryl) and grapefruit juice. If you experience any symptoms of serotonin syndrome, stop the DM and tell your medical doctor what happened. If the DM seemed to help with ALS symptoms, you might want to tinker with dosing or switching to a different antidepressant. Also, some of the other things you'll likely be taking (for example vitamin D, 5-HTP, and magnesium) have antidepressant action and may allow reduction in dosage of the prescription antidepressant.
- Zinc 50 mg/day as chelate(for example picolinate). Do NOT supplement with copper. There is a lot of information in this forum about zinc. You probably won't feel any immediate effects, just do it on faith. Available almost anywhere that nutritional supplements are sold.
UPDATE 23 Feb 2013: gluconate is the form preferred in treating Wilson's disease, and there's a pharmaceutical grade nutritional supplement form available that's designed for and marketed to Wilson's patients.
Kevin (and everyone else who DID NOT participate in the trial for that matter),
You take your total serum copper level and then subtract your total serum ceruploplasmin level times three from it to get your total free copper level. It should be in the 5-15 range. Anything over and you have too much free copper running around in your body (most likely accumulating in your brain and spinal cord). Interestingly enough, our controls did not (for the most part) have elevated levels seen in every PALS in our trial.
As a side note (if your doctor refuses to do the tests or you would prefer to get results quicker), you can purchase both tests at LEF (Life Extension foundation) for under $100 I believe around. Click Here For COPPER Blood Test Click Here For CERUPLOPLASMIN Blood Test
You simply take the orders which you actually print off from what they send via email to you (or they may mail the orders to you also) and you simply take them to Labcorp for the blood draw. Results are emailed to you. Simple as that again if your doctor won't agree to do it or you want the results quicker.
Also, here's the medical grade zinc we recommend to use (used in Wilson's patients too); Medical Grade Zinc Gluconate (the only one recommended from our trial results) ,
Note - If you are within the 5-15 free copper range, then simply take 50mg. If you are above that, I recommend 100mg (like the majority of our trial patients took) as too much free copper is within your body if above 15 (especially if it is way above that number of 15).
- Magnolia extract, for bulbar and UMN symptoms. In Chinese traditional medicine (and in my personal experience and that of others), especially effective in treating problems related to swallowing. Magnolia is rather new to ALS but it's gotten good reviews. The best dosage seems to be about 100 mg of the standardized concentrate, but that disappeared from the market late 2013 and now it's either 30 mg or 200 mg. I regard 200 mg as too high a dosage, and I expect that problems with that dosage unit will drive it out of the market. My source for 30 mg is www.roex.com. Give Magnolia extract a 2-day test drive. If no improvement in symptoms, stop. If improvement, continue, but be aware that there are theoretical reasons be concerned that tolerance may develop. My personal opinion is that this concern is unfounded but this is new territory and the verdict isn't in yet. Honokiol is a PPAR agonist, suggesting it may be of value to treat neurodegenerative processes, not just symptoms.
- 5-HTP (anecdotal report of benefit, information scattered, use search tool) 5-HTP may help with lower motor neuron symptoms such as cramps and muscle spasms. It may also help slow down neurodegeneration. Before taking 5-HTP, read and understand the precautions. 5-HTP raises serotonin levels (that's its purpose) but so do many other drugs (esp. many prescription antidepressants). Too much serotonin leads to serotonin syndrome. If you are at risk for serotonin syndrome, learn the symptoms in detail and watch out for them.
- Vitamin D3. Most PALS are shut-ins and without exposure to sunlight, they're deficient in this very important anti-inflammatory and calcium regulator. 5,000 IU/day. Best to also take Vitamin K2, which is a co-factor with D3.
- Magnesium taurate. Glutamate antagonist and GABA agonist. Magnesium deficiency is widespread in the modern diet. Only manufacturer of mag taurate I know of is Cardiovascular Research Ltd., but it's widely available. If you can't get it, then do magnesium citrate or orotate (NOT oxide) and taurine separately, those are even more widely available. Magnesium is a traditional remedy for muscle cramps. At magnesium dosages above about 200 mg per day, you may experience noticeable improvement in some ALS symptoms. Also be aware of the potential for "intestinal relaxation": with magnesium "more" isn't always "better". Most people can tolerate up to about 400 mg/day of magnesium without any difficulty. Since many people are magnesium-deficient anyhow, and since magnesium has so many health benefits, taking magnesium supplements makes good sense. Here is an excellent review of magnesium. The authors express concern that that taurate may be too tightly bound to magnesium to release either: however if the stuff isn't being pissed out as magnesium taurate, then the body is breaking it down into its components. So far no data if it's being pissed out as magnesium taurate. If you're concerned about it, you can always do magnesium citrate and then the taurine separately. However, there is some evidence that supplementing with several grams a day of taurine will cause the body to downregulate the taurine transporter molecule, defeating the purpose; and, that the said downregulation kicks in above some threshold (i.e. it's not linear with dosage). Therefore is it probably not a good idea to supplement with more than about 2 grams of taurine a day.
UPDATE: at some point in the future I intend to break up magnesium and taurine into separate categories.
- Curcumin (turmeric extract) An anti-inflammatory that crosses the BBB and which is also a heat shock protein inducer. Don't expect immediate noticeable effects. However among old-timers who are doing cocktail therapies, curcumin is almost always on their list. Curcumin is variously marketed as "turmeric", "turmeric extract", "curcumin", and "curcuminoids". Bioavailability is poor, which has led to the development of formulas which supposedly enhance absorption. LEF Super Bio-Curcumin is an example of such a product which is widely available.
NOTE: if you're concerned about the piperine in Super Bio-Curcumin, they've recently taken that out and replaced it with tumerones. And there's the phospholipid complex formulation Meriva.
- Glutathione support: NAC, selenium chelate, and milk thistle extract. N-acetyl-cysteine, 1.2 grams per day. Selenium, 100 micrograms/day (see post on page 3 of this thread for discussion). Milk thistle extract: commercial product is typically standardized to about 80% silymarin, 500 to 800 milligrams per day of extract is about right on dosage.
- Mitochondrial support: acetyl-L-carnitine (800 to 1200 mg/day) plus alpha lipoic acid (500 to 1,000 mg/day). NOTE: recently R-lipoic acid has become commercial available, with appropriate dosing about 1/3 to 1/2 of the regular (racemic) alpha lipoic acid.
- Water-pack sardines, several ounces a day. Yep, them little fishies. They're high in CoQ-10 (an important antioxidant), Omega-3's (anti-inflammatories), purines (raise uric acid levels), protein, and minerals. Darn near a miracle health food - IF you don't have gout. If you have gout, you already know to avoid sardines, you can get CoQ10 and Omega-3's in pill form almost anywhere that nutritional supplements are sold. Omega-3's are also widely available as hemp, flax, and fish oil. If you don't know if you have the metabolic disorder called "gout", before you start loading up on sardines, get your uric acid levels checked and then discuss the results with your doctor.
Suppose you can't do the sardines? In my opinion, when it comes to CoQ10, 100 mg/day of an advanced form (for example ubiquinol in oil) is probably enough, I haven't seen evidence that piling it on is better. My preferred brands are Dr. Mercola Ubiquinol 100 mg, and LEF Super Ubiquinol CoQ10 100 mg. When it comes to the Omega-3's, there are many ways to do that, from canned salmon (which is not high in purines like sardines are) to fish oil pills to flax oil to hemp oil and others. My personal preference is cold-pressed organic hemp oil inasmuch as it has a pleasant taste that goes well with almost anything. Hempseed is good stuff too, doesn't have that paint taste that flax has. Chia is another alternative, but tends to become a gooey mess.
- Citicoline (also called CDP choline), 400 to 1,000 mg/day. Try it for a couple days to see if you get a noticeable improvement in energy and reduction in "brain fog". Unclear if it has any effect on disease progression.
- Vitamin E complex (natural mixed tocopherols and tocotrienols). These can be purchased separately, but my personal preference is "TOCO-SORB", Jarrow #112026, which has everything in one softgel that's small enough to actually swallow. LEF has recently introduced Gamma E Tocopherol/Tocotreinols #00559 which as far as I can tell is the same thing.
- B-complex. Most so-called "B-50" formulations (for one a day dosing) seem fairly good, but read the label details before buying. B6 (pyridoxine) is important, but don't supplement more than 50 mg/day. Be warned also that quite a few nutritional supplements you wouldn't expect B-6 in contain B-6: read the fine print on the label. ...There's a whole slew of B-vitamins with different possible impacts on ALS, and it's going to take years to figure out what sort of combination is optimum. Some people are really big on B-12: if you're going to bother, go all the way to 5 mg/day methylcobalamin separately from your B-complex.
B-1 (Thiamine) deserves special attention Here's a summary I posted about page 5 in that thread: Most of the posting relating to thiamine is over my head, but I do skim through it anyhow hoping to absorb some information by osmosis. The encouraging PubMed is tempered by an anecdotal report of benfotiamine toxicity.
Here's my tentative summary of what I think I've seen so far.
- Thiamine deficiency is very common in ALS, probably because of genetic abnormalities and/or disease processes rather than inadequate dietary intake with food.
- Therefore supplementation is advisable at a level many times the RDA (1.6 mg). So-called "B-50" formulations usually contain 50 milligrams, or nearly 35 times the RDA.
- Because benfotiamine is lipophilic (and perhaps for other reasons also), it has pharmacological actions of types believed to be beneficial in ALS, which go beyond what you get from regular thiamine. Therefore benfotiamine is the preferred form of thiamine supplementation.
- Ordinary B-complex vitamin "pills" always include thiamine but to my knowledge never include benfotiamine. Therefore benfotiamime supplementation has to be done separately.
- Trimethylglycine (TMG, Betaine). The addition of TMG to the list emphasizes lower motor neurons: see Persevering's "Fasciculations" thread for more details. TMG is also a methyl donor which (like methylcobalamin B-12 and methylfolate helps to suppress the inflammatory factor homocysteine.
- 3nB (celery seed extract) anti-inflammatory, gliosis inhibitor.
- Ibuprofen anti-inflammatory, anti-gliosis, disinhibits neuron repair. See also apigenin.
- Peony root Peony is usually taken with non-DG licorice, which enhances its effects. Two anecdotal reports here of benefit, good underlying science. Usually thought of in terms of HSP up-regulation, peony is also a sodium channel inhibitor, which makes it a promising therapeutic for lower motor neuron disease particularly: see Persevering's "Fasciculations" thread.
- Resveratrol + niacinamide (nicotinamide) http://en.wikipedia.org/wiki/Nicotinamide Check your B-complex vitamin for its niacinamide content (if any). For more detailed discussion regarding this combo, see the paragraph below on "Nicotinamide riboside + resveratrol".
WARNING: if you're taking riluzole, be aware that resveratrol and several other natural substances may increase the toxicity of riluzole. I'd argue that if you're doing things that make sense, you shouldn't be taking riluzole anyhow. See also this thread wherein we discuss ideal dosing of resveratrol and come to a tentative conclusion that the customary high dosages found in most supplements nowadays are inappropriate, and that dosage should probably not exceed more than several tens of milligrams. Another link supporting the assertion that high doses are a bad idea.
Candidates for Addition to the List
The following are under consideration for addition to the list. Of course nobody needs my permission to go ahead and decide on their own to take them! ....The ones I regard as most promising (based on what I think I know at the moment) are at the top of the list, less promising stuff on the bottom.
Ethyl alcohol (the beverage kind) http://www.als.net/forum/yaf_postst52660_ethyl-alcohol-booze.aspx http://www.news-medical.net/news/20120813/ALS-risk-markedly-lower-among-alcohol-consumers.aspx Glutamate antagonist, GABA agonist, synergistic with glycine. "Candy is dandy but liquor is quicker", you'll know real soon if it provides symptomatic relief for you, plus it's cheap and needs no Rx. Epidemiological study showed drinkers are only half as likely to develop ALS as non-drinkers: the benefit would presumably extend to reduced rate of progression among those who get ALS anyhow. ......WARNING: Too much booze can be bad for you, I hope everyone knows that. Plus, some people readily become addicted to the stuff, which probably results from upregulation of NMDA receptors which would be a bad thing in ALS. So-- I'm not recommending getting smashed every day; and, if you have a family history of alcohol addiction, alcohol may be bad medicine for you. As I sometimes say, "Some people should drink, and some people shouldn't." It's up to you to figure out which category you're in. .......If you drink on a daily basis, it's a good idea to quit cold turkey for a week every now and then. Some people will experience withdrawal symptoms and others won't. If you experience withdrawal symptoms, probably the best thing to do is to taper off the drinking over a period of several weeks in order to detox without landing in the hospital, and thereafter don't touch the stuff. (Yep, I know this is contrary to AA dogma.)........ Going on a ketogenic diet? Sorry, the liver metabolizes alcohol into glucose, that's gonna work against you. .......If you drink, quaff a few pints (not all at once!) to support ALS research, no I'm not kidding: http://www.alesforals.com/ Since this is all about the hops, some pretty good IPA's are likely to come out of that project.
Nicotinamide riboside plus resveratrol Looks fairly promising, see especially the -NR thread. The related Nicotinamide is also worth investigation. The related NADH is so far looking like something we do not want to take. Although resveratrol seems to be the most popular candidate as a co-factor for NR, other molecules such as fisetin and even telmisartan have been proposed. NOTE: both theory and anecdotal reports indicate that NR should not be taken without a suitable co-factor.
Baicalin (Baical Skullcap extract) Complex interactions (apparently mostly favorable) in molecular pathways involved in ALS. http://www.als.net/forum/yaf_postst52727_Baicalin.aspx http://examine.com/supplements/Scutellaria+baicalensis/
Idebenone Synthetic analogue of CoQ10 said to be much improved over the natural stuff. It'd be on "the list" except that its commercial availability has diminished probably due to harassment by the FDA.
Creatine (long history of use in ALS, probably slightly beneficial, but several grams a day are needed)
Forskolin (cAMP agonist, information scattered, use search tool to search cAMP as well as forskolin) http://en.wikipedia.org/wiki/Forskolin UPDATE: there's now a forskolin thread here: http://www.als.net/forum/yaf_postst53906_forskolin-and-cAMP.aspx
Methylcobalamin B12 (methylating agent etc., info scattered, use search tool)
Vinpocetine There was a flurry of interest in it here a year or two ago. Usually thought of as a nootropic, but its sodium channel modulation properties make it of special interest as a prospective LMN therapeutic. Also inhibits degradation of cAMP, a good synergist for use with forskolin and/or methylxanthines if you're shooting the cAMP angle. http://en.wikipedia.org/wiki/Vinpocetine
Magnesium L-threonate http://www.lef.org/magazine/mag2012/feb2012_Novel-Magnesium-Compound-Reverses-Neurodegeneration_01.htm Supposedly gets magnesium past the BBB better than other mag supplements.
Sex hormone boosters and modulators DHEA, Tribulus, chrysin, natural estrogen and progesterone creams, Pueraria. Note: there is evidence that beta sitosterols (present in saw palmetto, nettle root, and pygeum) displace cholesterol in the formation of nervous tissue and may thus contribute to neurodegeneration.
Green tea extract (popular anti-aging agent, specificity for ALS unclear)
Pomegranite extract (popular anti-aging agent, specificity for ALS unclear)
Fisetin (new but popular anti-aging agent, specificity for ALS unclear)
Lecithin http://en.wikipedia.org/wiki/Lecithin http://en.wikipedia.org/wiki/Phosphatidylcholine http://en.wikipedia.org/wiki/Phosphatidyl_serine "Brain food", I'd rather get mine by eating eggs than popping pills. Mackerel and herring are high in PS (and also in purines if that matters to you for better or for worse). Soy-derived PS lacks the effectiveness of animal source PS; for this reason I don't think much of soy lecithin as a supplement.
Berberine http://en.wikipedia.org/wiki/Berberine http://www.als.net/forum/yaf_postst48627_Berberine.aspx http://en.wikipedia.org/wiki/Goldenseal (most common herbal source of berberine) http://examine.com/supplements/Berberine/ Note: There's lots of herbal supplements out there containing small amounts of berberine, but I haven't yet found one that contains berberine at meaningful dosage levels.
Butyrates HDAC inhibitors http://en.wikipedia.org/wiki/Butyric_acid http://en.wikipedia.org/wiki/Sodium_butyrate http://www.livestrong.com/article/557578-benefits-of-sodium-butyrate/ http://www.als.net/ALS-Research/SodiumPhenylbutyrate/ALS-Topics/ http://www.als.net/forum/yaf_postst53961_Sodium-butyrate.aspx NOTE: although butyrate could theoretically be offered as a nutritional supplement, to my knowledge it's available only as Rx medications.
Gardenia extract mitochondrial UCP2 agonist http://www.als.net/forum/yaf_postst52984_Gardenia-jasmoides-extract.aspx#370971 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699730/
Apigenin anti-inflammatory, anti-gliosis. See also ibuprofen. http://www.sciencedirect.com/science/article/pii/S0304394004013722 http://en.wikipedia.org/wiki/Apigenin http://www.swansonvitamins.com/swanson-ultra-apigenin-50-mg-90-caps
Luteolin closely related to apigenin and more widely available as a supplement.
Vitamin B-1 thiamine, benfotiamine If this makes it into the Prole Prote Toplist, it'll probably be as benfotiamine. http://www.als.net/forum/yaf_postst44708_Foot-drop-and-thiamine.aspx Note: anecdotal report of benfotiamine toxicity, second post in the following thread: http://www.als.net/forum/yaf_postst49223_Melanin-and-Vitiligo.aspx#334751 This was at high dosage, same patient chose to continue benfotiamine at a more moderate dosage.
Nutritional supplements, herbs, and OTC's rejected for Proletariat Protocol:
NOTE: This category does not mean the item is "bad", it only means that it seemed worthy of consideration, I did consider it, and regarded it as unsuited for the Proletariat Protocol.
inosine raises uric acid levels,disinhibits neuron repair esp. of axons. Probably worthwhile under careful medical supervision, but the risk of gouty arthritis and/or kidneystones mean it's not for newbies. http://en.wikipedia.org/wiki/Inosine Inosine has been discussed quite a bit here on the forum.
Cannabis and CBD For most patients, cost, quality of the product, and legal obtainability are problems. If the goddamn government would treat it like tobacco or alcohol, it'd be legal, affordable, and you could know what you were buying. US government has patented the use of cannabidiol to treat neurodegenerative diseases (which however wouldn't stop individuals), see http://www.als.net/forum/yaf_postst53669_Patent-6630507.aspx The inventors seem to think that dosing on the order of half a gram a day would be appropriate, but this seems to be extrapolation from in vitro research and so may be highly inaccurate. In the absence of clinical data, actual anecdotal reports would have more relevancy.
Ginseng http://en.wikipedia.org/wiki/Ginseng Although popular, the evidence in its favor is decidedly mixed, and unwanted side effects are common. http://www.als.net/forum/yaf_postst53520_GINSENG-.aspx
Ginkgo biloba Like aspirin, the stuff turns many people into "bleeders". (Like me for instance, this isn't just hypothetical.) Ginkgo might have value for someone who pays close attention to its anti-coagulation properties and makes sure they don't get into trouble with the stuff.
Methylene Blue TDP-43 aggregation inhibitor and other interesting actions. Not sold as a nutritional supplement, but available without Rx as a dye used in biological research. Failed in both SOD-1 and TDP-43 fALS mouse models, but that doesn't end interest in the stuff. http://www.als.net/forum/yaf_postst49812_Methylene-Blue.aspx http://www.als.net/forum/yaf_postst52580_Methylene-blue-Salubrinal-Guanabenz-and-Phenazine-were-each-tested.aspx
Prescription Drugs That Might Be Worth Taking
Research carefully both here and on the Internet, any Rx drug before taking it. The Proletariat Protocol is based on the assumption of no Rx drugs (since doctors usually won't cooperate). However, realistically speaking, most patients who are on a do-it-yourself protocol such as the Prole Prote will also taking one or more Rx drugs either with the cooperation of their medical doctor, or without it. The following list is not intended to be a comprehensive list of interesting Rx drugs, but may serve as a place to begin investigation. Those drugs which in my opinion show the most promise I have shown in boldface. BOILERPLATE: I am not endorsing anything on this list. The only drug on this list that I take specifically for ALS is Deprenyl (Jumex), but that doesn't mean anyone else should. I also take Telmisartan for hypertension and occasionally inhaled beta agonists and steroids for COPD.
Riluzole (I'll catch hell for even mentioning that stuff!)
Memantine NMDA receptor antagonist (Ca++ channel blocker), also exhibits activity at several other receptors of neurological interest. Clinical trial failed (of course) since it was not cocktailed. http://en.wikipedia.org/wiki/Memantine
Prozac and other SSRI's (risky if used with other serotonin enhancers)
Tricyclics (risky if used with other serotonin enhancers)
Prednisone and other corticosteroids
Dilantin (phenytoin) sodium channel inhibitor, long history of use as an anti-epileptic drug. http://en.wikipedia.org/wiki/Dilantin
Deprenyl (selegiline) and related drugs MAO-B inhibitor; may also inhibit apoptosis in neurons. Widely used to treat Parkinson's. http://en.wikipedia.org/wiki/Selegiline http://en.wikipedia.org/wiki/Rasagiline probably superior to selegiline http://www.als.net/ALS-Research/197/ClinicalTrials/ (rasagiline) http://www.als.net/forum/yaf_postst45697_selegiline-Deprenyl-vs-ciclosporin.aspx
Losartan and related drugs
Albuterol and other selective beta agonists
Theophylline and theobromine http://en.wikipedia.org/wiki/Theophylline Theophylline used to be an OTC bronchodilator but was reclassified as an Rx drug with the popularization of the safer inhaled beta agonist drugs. Theophylline raises cAMP, inhibits TNF-alpha, is an adenosine receptor antagonist, and histone deacetylase agonist. ......The closely related theobromine and caffeine have somewhat similar drug actions but with different profiles. http://en.wikipedia.org/wiki/Theobromine http://en.wikipedia.org/wiki/Caffeine
Valproic acid and valproates Sodium channel blocker, HDAC1 inhibitor, possible neuron apoptosis inhibitor. http://en.wikipedia.org/wiki/Valproic_acid http://en.wikipedia.org/wiki/Sodium_valproate http://www.als.net/ALS-Research/SodiumValproate/ALS-Topics/
Ramelteon ("sleeping pill", melatonin agonist) http://www.als.net/forum/yaf_postst53582_Rozerem-ramelteon.aspx
Copper chelating agents
Brintellix (Vortioxetine) new antidepressant different from the oldies, acts on a number of different types of serotonin receptors, Jason (jchexpress) reports definite improvement in motor neuron symptoms. http://en.wikipedia.org/wiki/Vortioxetine
Quinidine (often used in conjunction with dextromethorphan). With quinidine the problem is to find a product with sufficiently dosage: Nuedexta analogue would require 10 mg doses whereas the drug is usually available as 200 mg depot tablets.
Acamprosate NMDAr antagonist, GABA agonist, used to suppress alcohol withdrawal. http://en.wikipedia.org/wiki/Acamprosate
Gabapentin (Neurontin) GABA agonist, although its pharmacology is poorly understood. http://en.wikipedia.org/wiki/Gabapentin WARNING: http://www.wellnessresources.com/main/printable/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/#ref1
Pregabalin (Lyrica) GABA agonist closely related to gabapentin, Schedule V drug in the USA. http://en.wikipedia.org/wiki/Pregabalin WARNING: http://www.wellnessresources.com/main/printable/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/#ref1
Baclofen GABA-B agonist often used to control cramps and spasms, but once you're on it, stopping is difficult due to withdrawal syndrome. http://en.wikipedia.org/wiki/Kemstro (that link looks wrong but works)
Naltrexone (low dose protocol)
Edaravone (MCI-186) powerful nervous system antioxidant http://en.wikipedia.org/wiki/Edaravone
Mexiletine (sodium channel inhibitor) http://en.wikipedia.org/wiki/Mexiletine http://blogs.als.net/post/Mexiletine-channeling-ALS.aspx http://blogs.als.net/post/2013/03/14/Taming-the-Charley-Horse.aspx
Ivermectin (AMPA antagonist?) http://en.wikipedia.org/wiki/Ivermectin http://www.als.net/forum/yaf_postst50414_Ivermectin.aspx
'Retigabine and Flupirtine (Potassium channel openers) http://en.wikipedia.org/wiki/Flupirtine http://www.als.net/forum/yaf_postsm384498_Retigabine--potassium-channels.aspx#384498
Dichloroacetic acid (DCA) This stuff's a chemical, not an approved drug or natural supplement. Looks easy to obtain on the gray market. A lot of excitement over its purported anti-cancer benefits, including in neuroblastomas. http://thedcasite.com/ http://en.wikipedia.org/wiki/Dichloroacetic_acid
Statins (unless supplementing generously with CoQ10) This includes Red Yeast Rice, a natural source of lovastatin.
Anticholinergic antihistamines (including non-Rx OTC's)
Retinoids (related to vitamin A)
Drugs or supplements containing copper
Drugs or supplements intended for supplementing iron, unless for the purpose of correcting a diagnosed iron deficiency
Arguably the GABA agonists Neurontin and Lyrica: http://www.wellnessresources.com/main/printable/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/#ref1
WARNING ABOUT RILUZOLE
Neurodegener Dis. 2013 Dec 20. [Epub ahead of print] The Neuroprotection Exerted by Memantine, Minocycline and Lithium, against Neurotoxicity of CSF from Patients with Amyotrophic Lateral Sclerosis, Is Antagonized by Riluzole.
Abstract In a recent study we found that cerebrospinal fluids (CSFs) from amyotrophic lateral sclerosis (ALS) patients caused 20-30% loss of cell viability in primary cultures of rat embryo motor cortex neurons.
We also found that the antioxidant resveratrol protected against such damaging effects and that, surprisingly, riluzole antagonized its protecting effects.
Here we have extended this study to the interactions of riluzole with 3 other recognized neuroprotective agents, namely memantine, minocycline and lithium. We found: (1) by itself riluzole exerted neurotoxic effects at concentrations of 3-30 µM; this cell damage was similar to that elicited by 30 µM glutamate and a 10% dilution of ALS/CSF; (2) memantine (0.1-30 µM), minocycline (0.03-1 µM) and lithium (1-80 µg/ml) afforded 10-30% protection against ALS/CSF-elicited neurotoxicity, and (3) at 1-10 µM, riluzole antagonized the protection afforded by the 3 agents.
These results strongly support the view that at the riluzole concentrations reached in the brain of patients, the neurotoxic effects of this drug could be masking the potential neuroprotective actions of new compounds being tested in clinical trials.
Therefore, in the light of the present results, the inclusion of a group of patients free of riluzole treatment may be mandatory in future clinical trials performed in ALS patients with novel neuroprotective compounds.
© 2013 S. Karger AG, Basel.
PMID: 24356417 [PubMed - as supplied by publisher]
Other Protocols Worthy of Mentioning Here
Dr. Kathy Graham's commentary and critique of the Prole Prote: http://drkathygraham.com/2014/03/19/als-treatments-part-4/#more-1645 She's a physician naturopath in BC Canada who lost her mother to ALS a few years back, hence her interest in ALS. Some of her critique is a little off-base, in part because she was working with an early version of the Prole Prote, and because I'm not sure she fully understood what it is and what it isn't. However, some of it is definitely worth some investigation, for example her low opinion of curcumin and her high opinion of boswellia and berberine. Kinda sounds like she wants to be done with ALS now, but I sure wish we could get her posting here!
2004 LEF "Yellow Book" ALS Protocol This publication revolutionized DIY ALS therapeutics a decade ago. I regard the new 2014 "Blue Book" revision as inferior because of its emphasis on the drug pipeline rather than on DIY now.
Chelation Protocols The emphasis used to be on lead and/or mercury, but the attention has recently shifted to copper. I have a low opinion of protocols based on amalgam dental work: supplementing with selenium helps to protect against mercury toxicity.
Ketogenic diet In my opinion, it's valuable for athlete patients, and for non-athlete patients who are losing a lot of muscle mass. Lots of discussion here on the ALSTDI forum. I don't do it myself and haven't researched it well enough to integrate it into the Proletariat Protocol.
Anti-catabolic therapy Note how much this has in common with ketogenic protocols. Possibly a better approach than what we presently think of as ketogenic protocols? http://www.lef.org/protocols/health_concerns/catabolic_wasting_01.htm http://en.wikipedia.org/wiki/Glutamine
Deanna Protocol This is a general purpose throw-everything-at-it protocol which began as a personal protocol so complex that it was almost impossible for mere mortals to replicate. DP fans are trying hard to simplify the thing to make it easier for mere mortals to do. Philosophically it's traceable to the 2004 LEF "Yellow Book". I predict that as both the Deanna and Proletariat protocols evolve, there will be some tendency toward convergence. There's already quite a bit of overlap.
Mitochondrial Disease Protocol "Mitochondrial Diseases" can be loosely described as diseases caused by defects in mitochondria. Defective mitochondria play a key role in ALS, although defective mitochondria are not usually believed to be the root cause of the disease. However since ALS is many diseases, it's entirely possible that some ALS is a type of mitochondrial disease. The United Mitochondrial Disease Foundation obviously thinks so: http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=8032195 A number of therapeutics have been developed for treatment of mitochondrial disease, the United Mitochondrial Disease Foundation's list of which I've named "the Mitochondrial Disease Protocol" although it is actually a shopping list and not specific protocol as such. http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934635 Notice how much similarity there is between that "protocol" and what we bandy about in relation to motor neuron disease! Also notice that the UMDF has actually published such a list: where are the much larger ALS organizations doing the same? In ALS, it's patients and freelance medical doctors who are working on protocols.
The Ultimate Ducktail Back in Nov 2010, I proposed this therapeutic cocktail based on a fairly short list of carefully targeted "pills". I don't know if anyone ever used it as the basis of their own personal cocktail. If you have access to prescription drugs it's still worth a look. http://www.als.net/forum/yaf_postsm327843_The-Ultimate-Ducktail.aspx#327843
The Olly ADAR2 Protocol http://www.als.net/forum/yaf_postst53503p4_Gene-therapy-of-Tokyo-University-for-Sporadic-ALS-additional-information.aspx See page 4, post 3 Feb 2014. A work in progress, here's a glimpse: .....Olly wrote: Correcting declining ADAR2 seems to be the better of several other approaches so I'll start there. First a list of possible therapeutic substances followed by a very simple explanation of why they may work. In no particular order: IP6 - Inositol Hexakisphosphate - a cheap ready available supplement. 5-HTP - a cheap ready available supplement but can be dangerous if mixed with certain drugs causing serotonin overdosing. You may want to take B6 -daily amount only - as 5-HTP requires B6 to function. Thiamine (Vitamin B1) High fat diet Selective Anti-depressant/s
Anti-copper protocol This is a project led by fellow forum denizens jchexpress and inventor2, based on the theory that in many ALS patients, a key component of the disease process is misregulation of copper resulting in copper toxicity, having some similarity to Wilson's Disease. Stay tuned to their posts here, this could be a biggie.
Jock Science I love hiking in the desert mountains, and researched the DIY sports medicine literature for ways to temporarily extend my physical abilities and to recover quickly after serious hikes. My ability to go hiking seems to be gone now, but for several years the effectiveness of "jock science" made a huge difference in my life. ...To my knowledge, I'm the only PALS doing "jock science", probably because most PALS have progressed to a point where there's not much left to apply "jock science" to. It's also another pile of stuff that you have to do your own research and get it figured out for yourself.
Cannabis Otherwise known as "marijuana". Many ALS patients, including people who never thought they'd smoke weed, engage in cannabis therapy because it works for themin the area of symptom relief, both upper and lower motor neuron symptoms. It probably slows disease progression as well. Cannabis is arguably the single most useful therapeutic available for ALS, but it's mostly illegal. ....... Cannabis is actually two different pharmaceuticals, THC and its relatives (psychoactive) and CBD (not psychoactive). Both are valuable drugs but their pharmacology is different, and how they impact neurological symptoms and disease processes is only beginning to be unraveled. .......Since CBD is not psychoactive, the legalities surrounding it are less complicated. Dixie Botanicals (located in Colorado) has decided that CBD isn't even a controlled substance and has begun marketing it nationwide. I'd have put it on the Proletariat Protocol list except that the stuff costs several hundred bucks a month, that's not proletariat pricing. I suppose that in another couple years the price will come 'way down. NOTE: Echinacea also contains (non-psychoactive) cannibinoids and might have therapeutic value in ALS: however there seems to be very little research on this.
Anaesthetics Propofol is reported to have helped several ALS patients, but it has to be administered by an anaesthesiologist in a clinical setting. Just about the only way to DIY is to decide that you need a routine colonoscopy and hope you can get the anaesthesiologist to follow your instructions.
Chlorite therapy This is a do-it-yourself project. To do it, it helps if you know a thing or two about chemistry. Several patients have reported benefit. It's not clear how the stuff actually works.
So-called "Stem Cell" therapies These have been going on for decades for many diseases, and have produced virtually nothing. In ALS, there are a few isolated poorly documented reports of some benefit in bulbar and upper motor neuron disease, but even those (if real) are almost certainly a temporary result of the procedure itself and not of new neurons replacing dead ones. And forget LMN's, that'll never happen. .....There is some genuine stem cell research going on, but the field is rife with incompetency and outright fraud because there's so much popular press hype aimed at gullibillies, creating flocks ready to be fleeced. ......If you are being tempted by a stem cell clinic, first vet it here in this forum and on ALSUntangled.
Therapeutic regime targeted to lower motor neuron disease http://www.als.net/forum/yaf_postst49311_Are-Fasciculations-Good-or-Bad.aspx For most ALS patients, it looks like loss of the neuromuscular junction is the major driver of physical disability and of maintaining the neurodegenerative cascade. Unfortunately most of what we think we know about treating neurodegenerative disease is borrowed from biggies like stroke and Alzheimer's which don't involve lower motor neurons. We need a therapeutic regime targeted to the lower motor neurons, and the Fasciculations thread seems to contain enough information to at least get us pointed in the right direction: see also Aketri's "ALS theories summary" thread. ...We're making some progress on identifying promising LMN therapeutics and eventually an LMN protocol will probably be integrated into the Proletariat Protocol.
Therapeutic regimes targeted to specific types of ALS There is scattered here and in other places, information on the biological differences between the different types of ALS, which implies specifically targeted therapeutics are needed. It is my goal to be able to flesh out the Proletariat Protocol with those kinds of targeted therapeutics, but that's probably going to take at least several months, possibly years inasmuch as the data we have to work with is so little, so fragmented, and in many cases contradictory. ....We do however have the beginnings of such an approach with DM already on the list being targeted particularly to bulbar symptoms, and the ongoing work on LMN targeted therapeutics which is beginning to be pulled into the Proletariat Protocol.
Protocols targeting sex hormone levels Scattered through the forum is a lot of information relating to the possible influence of sex hormones on motor neuron disease, but it's never been collected all into one place for a good overview. There was a good thread recently on progesterone. Over the years, on this information, I've performed using the grey matter meat-technology CPU, a decimate-integrate-and-dump operation. What comes out of that particular information processing pipeline is this:
- Reduced hormone levels increase risk of developing ALS, and this is one reason why age and sex are such important ALS demographics.
- It's not just one hormone, it's all of 'em-- testosterone, estrogens, and progesterone.
- Probably the easiest way to raise hormone levels in a relatively balanced way, is to supplement with DHEA.
- There's a lot of angles to consider: hormones in OTC-supplement form, Rx hormones, tribulus, puereria, epimedium, anti-aromatase, finasteride, minoxidil, vitex, beta sitosterols, etc.
- But not to make it sound too dangerous or complicated, this is ALS we're dealing with, not acne! Doing nothing has a solid track record of poor outcomes, whereas we're not all dying like flies from overdoses of nutritional supplements. Therefore in my opinion (nonprofessional, your mileage may differ, etc.) if you're into serious ALS therapeutics and over 50 years of age, supplementing with 100 mg a day of DHEA is a good place to begin targeting hormone levels. Preferably getting hormone levels tested occasionally, and preferably staying current on the subject and changing your approach if warranted based on new or additional information.
Guys, pay attention to possible BPH. The traditional supplement fix for that is beta sitosterol plant extracts, which however may possibly represent a long-term risk of neurotoxicity (information on that is rather sparse, sorry!). There's other stuff like chrysin and pollen extract and boswellia which however don't have as solid a track record in treating BPH as beta sitosterol does.
The OFF-LABEL PROTOCOL http://www.als.net/forum/yaf_postst53854_The-OFFLABEL-PROTOCOL.aspx This thread is intended to develop a protocol based on a mix of Rx drugs prescribed off-label, and herbal and nutritional supplements. So far (17 May 2014) unfortunately not much has happened in that thread.
REFERENCES AND RESOURCES
The background of this project is found in the following thread: http://www.als.net/forum/yaf_postst53404_The-price-tag-of-hope.aspx
Aketri's "ALS Theories Summary" thread: http://www.als.net/forum/yaf_postst48203_ALS-theories-summary.aspx A long and difficult read, but arguably the best thread on ALS anywhere on the entire planet. Anyone who is putting together their own DIY formula needs to plow through this thread.
http://www.lef.org/protocols/neurological/als_01.htm Best short introduction to the subject, greatly revised from the contents of the 2003 edition of the Big Yellow Book which still afford good reading. You probably know Life Extension Foundation, but if you don't, becoming a member is worth it. Wide range of leading-edge herbs & supplements, every late spring they have a sale on medical testing, and they are affiliated with a USA mail order pharmacy which is good at saving you money if you have appreciable prescription drug expenses. Of those who have reported doing things that helped them with their ALS, many have said that LEF played a key role in their education and in supplying good nutritional supplement products. I'm one of those people.
http://violentmetaphors.com/2013/08/25/how-to-read-and-understand-a-scientific-paper-2/ Scientific papers are hard to read and make sense out of, especially if you're not familiar with the subject matter. This web essay explains how to get started, and the emphasis is on medical science. Its biggest weakness is that it begins with the assumption that you have access to the whole paper, whereas the reality is that most of the time we only have access to the abstracts.
http://www.als.net/forum/yaf_postsm387608_New-website-to-comparefilter-ALS-therapeutics-and-protocols.aspx#387608 "TuKa's List". A resource for comparing various ALS therapeutic protocols and their ingredients.
http://www.vitaminshoppe.com/store/en/vitamins_minerals/index.jsp My primary source for herbal and nutritional supplements. Used to buy online until they built a bricks & mortar store in El Paso, so now I shop in person. They carry many LEF products.
http://www.antiaging-systems.com/ My primary source for supplements and a few Rx items that have to be obtained internationally. I used to be able to go down the street and across the "river" to get some stuff in Mexico, but in 2009 the drug wars got too nasty and I haven't been back. At last report (Jan 2014) they're taking Visa and bank drafts, but not any other credit cards or bitcoin.
http://www.nutritionexpress.com/ Used to be my primary mail-order source for "jock science stuff". However nowadays I can get most of that at the VitaminShoppe locally.
http://www.patientslikeme.com/als/community Good tools for keeping track of your "disease progression" and comparing it to that of others, and "social networking" with other ALS patients and their caregivers. I recommend staying out of the forums, they're a reminder that half the population has an IQ below 100 and they also get ALS. (Nearly all ALS forums are dominated by bozos, ALSTDI's forums being an exception.) Once upon a time I was a member of PLM but they kicked me out and erased my profile. I believe my posts are still in the forum archives.
http://www.dixiebotanicals.com Located in Colorado, source of mail-order CBD. To my knowledge they're presently (Jan 2014) the only online source shipping nationwide, but I expect it won't be long until they have competition.
http://www.swansonvitamins.com/ Major online retailer of nutritional supplements, etc. Swanson was around a long time before there was an Internet. I haven't used them much, but have been happy with them as a supplier. They're a favorite supplier of some PALS, and have a far broader range of stuff nowadays than they used to. Nowadays they often have stuff that's almost impossible to find elsewhere.
http://www.iherb.com Another popular online supplier of nutritional supplements. Don't recall having used them myself.
http://www.roex.com/ Relatively new company, seems to have been put together from the pieces of a couple other suppliers that went belly up. It's where I get magnolia extract.
http://www.lef.org/Vitamins-Supplements/Blood-Tests/Blood-Tests.htm Wide selection of medical tests (primarily bloodwork)available mail-order, the blood will be drawn at a local medical lab under contract. The product offering includes ceruloplasmin and copper, two tests that all ALS patients should probably get but medical doctors don't know that. Every late spring they have sale with huge discounts.
http://alsuntangled.com/ Unique resource based on a social networking model, their primary mission is to research and to publish reviews on various proposed ALS therapeutics. Some would say they tend to err too much on the side of caution, but they're far less biased than the well known "Quackwatch" which is prone to label anything that didn't come from Big Pharma as quackery. I just now checked out Untangled's report on Prevagen: it looked fairly well done and it convinced me that Prevagen probably doesn't belong in anyone's Pile of Pills (although someone else's informed opinion may differ).
http://www.als.net/forum/yaf_postst48193_Peony-root-and-paeoniflorin-long-essay.aspx People sometimes ask me what my protocol is or has been. There are in the Peony thread several links to snapshots of my protocols as they have evolved over time. This thread is also the basic resource here on peony if you happen to be interested.
http://www.naturdoctor.com/Chapters/Research/ALS/ALS1.html Lengthy and well-researched 9-part essay on ALS and potential therapeutics. I disagree with the author on several points, esp. his recommendations to increase SOD1 and to supplement with copper, which at one time seemed to make sense, but nowadays are pretty much proven wrong. Despite a few glitches like that, overall it is an excellent essay and a heckuvalot easier to read than Aketri's ALS theories summary thread.
Somewhat off topic but great information on this als online genetics database and this ALS gene website.
The genetics of ALS is in the very early stages of being unravelled. At this (Jan 2014) stage it's nearly useless to patients other than a few known familial cases. It's looking like in sporadic two main groups may emerge: TDP-43 and SOD-1, and that the corresponding targeted therapeutic approaches will be somewhat different.
http://www.yorku.ca/hamadeh/CLINNUTRTABLES2009.pdf Emphasis on ALS from the perspective of antioxidant therapy. In vitro, in vivo, and human trials of various nutritional supplements, a summary of what's been done. 28 pages!
http://examine.com/ This is a website which collects information on nutritional and herbal supplements and summarizes the information in convenient form. All kinds of stuff you never heard of. Excellent resource esp. for unusual stuff, but their perspective is often different from ours and that has to be considered when relying on their information.
Questioner made a great find. Here's the thread http://www.als.net/forum/yaf_postst53895_Review-of-nutritional-supplements-for-ALS.aspx and here's what he found http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631353/ It's a review of the scientific basis of DIY cocktail therapies, the lead author of which was none other than Dr. Jeff Rosenfeld, Ron's hero neurologist. Recommendations don't get better than that! I'm hoping someone will copy the document into Aketri's ALS Theories Summary thread.
http://www.als.net/docs/pdf/ips/Full_Experimental_Protocol.pdf ALSTDI has embarked on a research project that integrates genome analysis with in- vitro "drug trials" on tissue samples. This is a revolutionary technology, we're very fortunate to have something like this going on with ALS. Most diseases that aren't in the top 10 get very little research. ........ It'd be easy to explain the expected long-term benefits from this research project, but unlike most research this one stands a chance of benefitting a few PALS while they're still alive. How? If you have a list of your genetic abnormalities, that provides clues to potential therapeutics that may already be available. An obvious example is that if you've got genetic abnormalities known to be associated with dysregulation of copper, you probably really oughta be taking zinc. 2014 was a landmark year, the year we began to develop therapeutic protocols targeted to different types of ALS. On this very forum. It looks like 2015 will also be a landmark year, the year in which genome sequencing finally becomes relevant to therapeutics. Thanks to ALSTDI.
Short Essay: ALS Fads
The field of ALS therapeutics goes through fad cycles. I'm constantly tweaking my therapeutic regime based on what people are posting about that sounds interesting at the time. .....What gets forum action doesn't necessarily have anything to do with the merit of the stuff in question. It can have to do with availability of information about the stuff, with availability of the stuff itself, or with reports from PALS of supposed benefit or lack of benefit. ....Several years ago, lithium was all the rage: that probably won't happen again with lithium. Nowadays, DM is at the top of my Proletariat Protocol list: it was clinically trialed 'way back when and the results were evidently bowdlerized, the whole time it was a well known NMDA receptor inhibitor, and here we are with the stuff in clinical trial again and more useful information coming from DIY'ers than out of the clinical trial. ........As an ALS patient researching potentially useful therapeutics, you've got a huge pile of possibilities to choose from and not much time to decide and act. I can't tell you to stick with the stuff that's proven, because the only protocol that meets the criterion of proof is the do-nothing protocol and I don't like what it proves. ..... So, I don't discourage newbies from trying stuff that may not have won any popularity contests here. What interests you might be something new (like Gastrodia)or something old that somehow failed to trigger excitement (ibuprofen?). If it looks affordable and safe and the evidence in its favor dials your number, have at it! Sure beats "placebo therapy"!
Short essay: What does "neuroprotective" mean?
The word is bandied about here as though it actually meant something important. Sure sounds important when the topic is ALS.
The list of substances described as "neuroprotective" in the PubMed Pile is almost limitless. Most commonly, a substance is described in this way for one of the following reasons:
- It inhibited damage or death to neurons in in vitro testing, when the neurons were exposed to some kind of agent known to cause damage to neurons.
- In an animal model of stroke or other localized experimentally induced ischemia, the substance reduced death and/or improved recovery. The underlying molecular biology is almost always either modulation of glutamate, or modulation of glutamate receptors.
In the context of ALS therapeutics, this isn't very good news.
In vitro research is useful for discovering molecular pathways. However the molecular biology of living animals is very complex, and what works in the test tube usually doesn't work in clinical trials (often doesn't even work in lab animals engineered for the purpose).
In my opinion, stroke and related experimental ischemias are nearly worthless as models of neurodegenerative processes.
Substances trialed on animal models of neurodegenerative disease, when successful in those models, almost never translate to provably useful therapeutics in humans with those purportedly same diseases because the disease in humans is so variable, unlike in the engineered animal strains which have variability bred out of them.
When it comes to the underlying molecular biology of substances which get referred to as "neuroprotective", there are two big groups: antioxidants, and glutamate modulators (inclusive of GABA agonists etc.). Huge amounts of those kinds of stuffs have been thrown at ALS patients, with very little to show for it.
This does not mean I regard such things as useless, only that in human ALS they're not much use all by themselves. I regard antioxidants and glutamate modulators as essential ingredients in any promising cocktail therapeutic regime.
Also, keep in mind that antioxidants are not all the same and neither are glutamate modulators. These mechanisms of action include many actual molecular pathways, and the substances in question often have pharmacological activity beyond antioxidation or glutamate modulation. Therefore it's possible that something that's been labeled as an antioxidant or glutamate modulator (or words of generally similar meaning) could prove to be an extremely valuable therapeutic.
Cross-posted on 15 Feb 2014 from Nemesis' "The Metabolic Core of ALS" thread, please note the implications it has for the efficacy or lack of same of "protocols" including the Proletariat Protocol. When I get some time I'll rewrite this and integrate it into the earlier part of this document.
cell-specific mSOD1 in neurons, doesn't cause ALS in mice, while cell-specific mSOD1 in astrocytes makes them toxic to the extent that they kill motor neurons expressing WT SOD1.
Labwork using different methods substantiates this basic principle, and extends it to sporadic ALS in humans. This is well known (at this point) in the ALS research community but easily forgotten because it's so counter-intuitive.
Most therapeutic interventions proposed for ALS focus on helping the neuron survive the attack it's under. A few therapeutic interventions (generally in the "anti-inflammatory" category) hope to reduce the intensity of the attack or to eliminate it. The Proletariat Protocol includes therapeutic interventions in both categories.
The underlying theory of the Prole Prote is that of the "neurodegenerative cascade", a theory which includes as a basic element the idea that damaged neurons release proinflammatory cytokines which sustain the attack. The "neurodegenerative cascade" theory does not address the question of why the attack began in the first place.
It appears that at least in the case of SOD1 fALS, the attack is going to proceed because of a fundamental defect in the astroglia, without dependence on release of proinflammatory cytokines by damaged neurons to maintain the attack. Therefore a protocol such as the Prole Prote, although it may prolong life somewhat in an SOD1 sALS patient, is not going to halt the disease much less make recovery possible. This is more than just a limitation of the Prole Prote, it indicates a fundamental inability of the G93a mouse model to be used for testing therapeutics intended for a sporadic ALS patient population.
The problem goes beyond SOD1 fALS, it extends to any case of ALS which is initiated and sustained by a fundamental genetic defect in the astroglia.
I'll stretch this line of reasoning a bit further. ALS is not "a disease", it is a collection of many different diseases, a fact better grasped by replacing the misleading acronym "ALS" with "Motor Neuron Disease". There are credible reports of varying degrees of therapeutic success, mostly with cocktail approaches that have a lot in common with the Prole Prote. And, reports of no apparent benefit as well. Some of this variability in results is obviously attributable to the fact that every DIY'er does their cocktail differently, but some has to be attributable to variability in what disease is actually afflicting the patient. And the patient rarely knows what disease that is, other than that is some kind of nebulous "ALS" thing.
There have been a few reports of definite therapeutic success from monotherapies: joelC (IV glutathione) and (as I recall) an animal model using a copper chelator and another using a small-molecule antioxidant. The animal models aren't representative of sporadic (that's not even possible with animal models), they're usually a mutant SOD1 model.
Somewhere along the line I've read of purported effective "alternative medicine" treatment of gliomas, but paid little attention to it because I didn't think it was directly applicable to ALS. Nemesis' post has changed that perspective.
Because of the importance of this line of reasoning to therapeutic strategies, I will cross-post some version of this to a couple of other threads.
Dave Johnson's case history
People occasionally ask me about my personal case history. Rather than retelling it over and over, I'll stick a summary here where it's easy to find.
Onset early 2005, upper and lower motor symptoms, rapid progression, no bulbar. Usually required crutches for ambulation. Self-diagnosed Dx late spring, confirmed by neurologist summer and reconfirmed by another neurologist in October. Some respiratory impairment Aug through Oct.
Had been researching therapeutics and began a protocol generally similar to the Prole Prote in August. At that time I didn't know anyone else who'd done this type of protocol and frankly my expectations were low. During the fall, symptoms were highly variable but my worst days were no worse than they had been earlier in the year, and on good days I decided not to use the crutches any time I didn't really have to. By November the respiratory impairment (diaphragm involvement) was gone. By December most of the time I didn't need crutches.
Began Jan 2006 with the crutches in the closet. During winter-spring re-learned how to run and to kick (had to figure it out, not just a matter of regaining strength, similar to what stroke victims describe) and by early summer was nearly fully recovered. Next several years did some good mountain hiking upon occasion, but the last 4 years or so symptoms have been returning enough to cause impairment esp. upper motor neuron. Last good hiking was July 2012. Oct 2013 I went hiking and people were asking if I needed to be rescued, it was that ugly. I knew my limits and got out. Despite application of "jock science", I suffered a neurological setback (sometimes back on crutches). Since I hadn't had a setback like that before, I figured it was now "end game". However, gradually recovered over a period of a couple months. These days (spring 2014) I use a cane but don't need crutches.
I'm hoping for some good new developments in therapeutics this year to keep me going. Zinc gluconate and 5-HTP are now regular items in my diet, and switched to LEF Peony Root Extract which is much higher dosage than the Roex I had been taking. Magnolia has also been a help, suppressing vagus hyperreflexia (esophageal spasm etc.) to where I can reliably get the Pile of Pills down. The vagus hyperreflexia I've had for about 15 years, and doesn't seem to be related to the ALS.
Regarding the specifics of my therapeutic regime over time, the information is scattered. There are links to most of the pieces in the Peony thread http://www.als.net/forum/yaf_postst48193_Peony-root-and-paeoniflorin-long-essay.aspx
18 May 2014 The following is a sneak preview of the next "Pile of Pills" and instructions what to do with it. The information is arguably useful to anyone about to embark on some version of the Proletariat Protocol. I'll eventually transfer this information to the Pile of Pills thread when I'm back to actually putting piles of pills into boxes.
NEXT PILE OF PILLS
CONTENTS OF THE PILE
- Wal-Tussin DM liquigels, 15 mg
- Trimethylglycine caps, 750 mg
- 5-HTP caps, 100 mg
- Gamma E toco's softgels,470 mg
- Licorice root extract caps, 450 mg
- Vit D+K+iodine caps, approx 4 mg
- Zinc (as gluconate) caps, 25 mg
- Milk thistle extract softgels, 460 mg
- Ibuprofen caplets, 200 mg
- CDP-choline caps, 250 mg
- Celery seed extract caps, 75 mg
- B-12 methylcobalamin tablets, 5 mg
- Vit B-50 complex caps, 850 mg
- Curcumin complex caps, 400 mg
- Carnitine complex caps,700 mg
- R-lipoic acid caps, 300 mg
- Magnolia bark extract caps, 30 mg
- Resveratrol tablets, 17 mg
- Niacinamide caps, 250 mg
- Benfotiamine caps, 150 mg
- Selenium (methionine) tabs, 0.1 mg
- N-acetylcysteine caps, 600 mg
- Peony root extract caps, 600 mg
- Ubiquinol liquicaps, 100 mg
- Magnesium (taurate) caps, 125 mg
PILE OF PILLS: DISCUSSION
First, the boilerplate
You know I'm not a medical doctor, you know that this pile of pills comes with no warranty other than there has been no intentional material misrepresentation on my part, and you acknowledge that nobody knows the outcome of taking this pile of pills. It's a box of stuff that you want because having informed yourself regarding its contents, you believe it might be beneficial to you. You understand that my "advice" and "recommendations" regarding this stuff comprise nonprofessional (although hopefully well-informed) opinions, and not more than that. If you utilize materials or information that I have provided, you acknowledge that you are doing so having researched these things yourself, and having done so that you are acting on your own personal knowledge and opinion.
This Pile of Pills corresponds loosely to the toplist of the Proletariat Protocol. This Protocol comprises more than a pile of pills: it also involves diet and lifestyle practices. Those are things I can't ship in a box, you have to take responsibility for them yourself.
There's a lot of pills there, and if you simply start out the first day with the full regime, if you have unwanted side effects (or for that matter immediate beneficial effects) you won't know what caused them.
The Pile of Pills does include several items the primary purpose of which is symptomatic improvement. However the Proletariat Protocol is designed around the theory of the “neurodegenerative cascade”, and every day that the neurodegenerative cascade continues, additional permanent damage is done. Therefore, I suggest starting out with stuff that's not likely to have any immediate symptomatic effect, but which may begin targeting neurodegenerative processes. A few people may have undesirable reactions to "pills" that otherwise rarely cause problems, and if you're one of those few people you need to find out immediately. More on this in the next section.
Before taking any “pill” (even a prescription from a doctor), first go on the Internet and read at least the following pieces of information:
- The information about the product on the manufacturer’s website. It’s important to know what the “pill” actually is.
- A Wikipedia article on the substance in question.
- The Proletariat Protocol, see what information may be there about the stuff. ……...These are pills you may be taking every day for years, so it’s not unreasonable to spend half an hour researching each one before beginning to take it. You might even decide based on that research that you don’t want to take the “pill” after all. ALS therapeutics are a do-it-yourself project, every patient’s case is different, and everyone’s life circumstances are different. Therefore you have to be the one to decide what to take or to not take, those are decisions nobody else can make for you.
The science of ALS therapeutics is in its infancy. Almost nothing is known for certain, and there are constantly new developments in opinions regarding therapeutics for ALS. Therefore please keep in touch with what’s happening on the ALSTDI Treatments Forum. I realize that for most people it is not practical to read everything posted, there’s just too much of it, and most folks lack enough education in molecular biology to understand it even if they do read it. There are two ways to keep the effort of continuing education manageable.
- When there is a new development which I believe warrants a revision in the information in the Proletariat Protocol document (first post in the thread), I update the document. So if you check the Protocol twice a month, you’ll be reasonably up-to-date on that.
- When you see a thread pop onto the first page of the forum the topic of which concerns something you’re actually taking or doing, check the new posts to see if they’re relevant to you.
- If you have a question, post it in the appropriate forum. That’s a good way to get a quick response from people who might actually know something about it. What’s more, we often learn from questions, so questions are welcome.
Stuff to begin with
I recommend to begin immediately with the following items that are extremely unlikely to have any immediate effect, either positive or negative. If there is a negative effect, stop taking all of it and reintroduce the items one item at a time, a new item every two days. If a particular item seems to have unwanted side effects, omit it. …..What you perceived as an unwanted side effect was probably just a coincidence. Later on when your “pill regime” has stabilized, you can reintroduce it again to see what happens.
LEF N-Acetyl-L-Cysteine (NAC), 600 mg x 60 caps. LEF #01534, cost $10. Dosage: twice a day. Supports synthesis of glutathione, a key antioxidant esp. for neurons, and also an immune modulator. NOTE: there are anecdotal reports of symptomatic improvement after a few days of NAC supplementation. For this reason I regard NAC as the very first best thing to start out with. WARNING: if you have ever experienced cysteine urinary tract stones, skip the NAC until you’ve first consulted with a medical doctor, then decide which risk you’d rather take.
Vitamin Shoppe Selenium (methionine) tabs, 0.1 mg x 300, cost $14. Dosage: one a day. Selenium is an essential mineral for synthesis of glutathione.
LEF European Milk thistle extract softgels, 460 mg x 60, #01822C, cost $17. Dosage: one a day. This is an advanced formulation. Milk thistle extract supports glutathione production by the liver. Glutathione is an antioxidant of critical importance to neurons. It also modulates immune function. NOTE: the bottle recommends dosage 2 times a day. In my opinion they’re just trying to sell more pills. With this advanced formulation, once a day should be sufficient.
Allergy Research Group TMG (Trimethylglycine) caps, 750 mg x 100 , cost $18. Dosage: twice a day. Methylating agent (helps suppress homocysteine, a cause of inflammation), and is synergistic with zinc and alcohol at the neuromuscular junction in protecting against excitotoxicity. NOTE: Yep, I said alcohol. As I explain in the Proletariat Protocol document, “some people should drink, and some shouldn’t”. There are several reasons to reason to think that alcohol is beneficial in ALS among people who should drink. If you’re among those who know from prior experience that you shouldn’t drink, I don’t recommend starting just because you developed ALS.
LEF Gamma E Tocopherol/Tocotrienols, 470 mg x 60 softgels. LEF #00559, cost $25. Dosage: one a day. Antioxidant support of particular importance to neurons. Best absorbed if taken with a meal that includes fats/oils.
LEF Vitamins D and K with Sea-Iodine, 60 capsules. D=5,000IU, K=1.1mg, iodine=1mg. LEF #01741, cost $15. Dosage: one a day. Vitamin D is anti-inflammatory, and Vitamin D and K together manage the body’s storage and use of calcium. Iodine supports thyroid function.
Vitamin Shoppe B-Complex 50, 850 mg x 100 caps, cost $10. Dosage: one a day. General neurological and health support. The various specific B-vitamins play different roles in the body. This particular product seems well balanced for use in ALS, and the niacin is in the form of niacinamide in order to avoid “niacin flush”.
Twinlab Mega B-12 Dots (sublingual tablets), 5 mg x 60, cost $ 11. Dosage: 1 a day. I thought this was methylcobalamin but reading the fine print I see it’s cyanocobalamin which is widely regarded as an inferior form, sorry! I’ll be more careful next time. Unlike some vitamins, B12 is safe to megadose (this is 800 times the RDA). Many people regard oral B-12 megadosing to be beneficial in neurodegenerative disease. I regard that evidence as flimsy. Nonetheless the stuff is harmless, it doesn’t even need to be swallowed, and it might help. NOTE: since the B-Complex also contains B-12, it’s best to take the B-12 “dots” during the meal that you don’t take the B-Complex, therefore maintaining a more stable blood level of B12.
Dr. Mercola Ubiquinol (CoQ-10) liquicaps, 100 mg x 30, cost $22. Dosage: one a day. Ubiquinol is the preferred form of CoQ-10, a mitochondrial antioxidant. Best absorbed if taken with a meal that includes fats/oils.
Natural Factors Celery Seed Standardized Extract (3nB) caps, 75 mg x 60, cost $14. Dosage: one a day in the evening. Anti-inflammatory of special interest in neuroinflammation. NOTE: “in the evening”, because it alternates with the somewhat similar acting curcumin which is taken in the morning. The reason for 3nB in the evening (and not the morning) is because 3nB is probably the more effective of the two in suppressing inflammation associated with gout, that most often develops during the night.
If all that goes fine for several days, then:
LEF Super R-Lipoic Acid, 300 mg x 60 caps, #01208, cost $31. Dosage: twice a day. Mitochondrial antioxidant. The R- form of alpha lipoic acid is the preferred form. A few people experience mild stomach upset with alpha lipoic acid. If this happens, my recommendation is to keep taking it anyhow, your stomach will probably quickly accommodate to it.
LEF Optimized Carnitine (Carnitine complex) caps, 700 mg x 60, #00916, cost $22. 400 mg ALC, 150 mg ALC arginate, and 150 mg Glycine propionyl-L-carnitine. Dosage: two a day. Mitochondrial energy chain support. Traditionally paired with alpha lipoic acid.
LEF Super Bio-Curcumin, 400 mg x 60 caps. LEF #00407, cost $24. Dosage: once a day in the morning (see previous comments on 3nB). Anti-inflammatory, crosses BBB. This formula is an advanced formulation. WARNING: If you have a history of gall bladder problems, do not take this without first consulting with a medical doctor.
If that goes well for two days, then introduce the following, one at a time every two days:
Extreme Gluzin Zinc 25 mg (as gluconate) x 120, Extreme #V-1431, cost $22. Dosage: twice a day immediately before meals. The purpose of zinc is to inhibit copper toxicity, and the gluconate form taken immediately before meals is preferred because it inhibits absorption of copper from the digestive tract and itself has high absorption. If your copper bloodwork test results suggest high copper, 3 times a day is probably more appropriate dosing. NOTE: A few people might experience mild digestive upset or odd taste sensations: my recommendation is to continue even if this occurs, your system will probably get used to it.
Cardiovascular Research Ltd. Magnesium Taurate, 125 mg magnesium capsules x 60, Vitamin Shoppe item CV-1094, cost $11. Dosage: two capsules twice a day. Magnesium and the amino acid taurine are inhibitors of glutamate excitotoxicity, usually taken separately but this particular formula combines them. NOTE: a few people may experience a mild laxative effect from the magnesium. If this occurs, my recommendation is to cut back to one capsule twice a day, and then boost it to 2 caps twice a day a week or so later.
Well at Walgreens Ibuprofen 200 mg caplets x 100, item #500733, cost $7. Dosage: one caplet twice a day. Anti-inflammatory. Note: a few people may experience stomach upset. If this occurs, discontinue. Your system won’t get used to it.
Twinlab Resveratrol Max Dots (sublingual tablets), 17 mg x 60, cost $15. Dosage: one caplet twice a day. Widely believed to be “healthy stuff”, although the underlying science is complex. In my opinion, this relatively low dosing level is to be preferred over the megadose “pills” commonly being marketed these days. Resveratrol is a co-factor with niacinamide.
Jarrow Niacinamide (nicotinamide) capsules, 250 mg x 100, cost $9. Dosage: one capsule twice a day, take with resveratrol. Note: although niacinamide isn’t supposed to produce the “niacin flush”, a few people may experience some flushing anyhow, a nuisance which goes away typically in about 15 minutes. Also: some patients within several days of niacinamide supplementation may experience symptomatic improvement in lower motor neuron symptoms. Note: if you are supplementing with nicotinamide riboside, that stuff replaces niacinamide so don’t do the niacinamide. The 50 mg of niacinamide in the B-50 is okay, don’t worry about that.
Doctor’s Best, Best Benfotiamine capsules, 150 mg x 120, cost $23. Dosage: one cap per day. Benfotiamine is a semisynthetic special form of the B-vitamin thiamine which may be of special importance in treating neurodegenerative disease and which also inhibits the formation of toxic protein-sugar complexes (glycation).
Items that may provide quick symptomatic improvement, and possibly long term benefit:
Go several days between each item before introducing a new one into your protocol. This way you can tell what produced symptomatic improvement and what doesn’t. ……...Items which produce no symptomatic improvement may nonetheless be beneficial in slowing neurodegeneration, so just because an item doesn’t produce symptomatic benefit doesn’t necessarily mean you shouldn’t be taking it.
Walgreens Wal-Tussin (R) liquid-filled capsules, 20 to a bottle, item #669854. Each cap 15 mg dextromethorphan hydrobromide. Cost $6. Appears to be the same thing as Robitussin Long-Acting Cough-Gels (R). Dosing: 3 times a day. If you have pseudobulbar or bulbar symptoms, this is one of the first things you should try, maybe even the first thing. Many bulbar/pseudobulbar ALS patients experience significant symptomatic benefit from dextromethorphan. You’ll know within 2 days if it helps. If it doesn’t help, discontinue it unless you believe it may slow disease progression (there’s reason to think it may). WARNINGS: Some people metabolize dextromethorphan slowly, causing buildup over several days. If (especially after several days) you notice unusual mental symptoms (which could be just about anything), stop taking it. If after several days of no dextromethorphan the unusual mental symptoms have disappeared and bulbar/pseudobulbar symptoms are returning, then resume dosing at one capsule per day in the morning. Then increase dosage every several days up to a maximum of 3/day or until you get either symptomatic improvement or the unusual mental symptoms return. If the unusual mental symptoms return before you get symptomatic improvement, dextromethorphan is not for you, sorry! ALSO: If you are taking prescription drugs for depression, St. John’s Wort, or tryptophan or 5-HTP or other potent serotonin precursor, do not take dextromethorphan until you have informed yourself about potentially dangerous “serotonin syndrome” and have either discussed with your neurologist or have decided to proceed very cautiously knowing how to manage the risk. AND: dextromethorphan may be synergistic with dopamine-enhancing Parkinson’s drugs: therefore if taking Parkinson’s drugs do not take dextromethorphan unless you’ve had a discussion with your neurologist about recognizing symptoms of excess dopamine.
Jarrow 5-HTP caps, 100 mg x 60, cost $19. Dosage: one cap twice a day. This is a serotonin precursor. Although we usually think of serotonin in the context of treating depression, actually serotonin plays an important role in neurological health including that of motor neurons. Although the primary purpose of taking 5-HTP as a therapeutic in ALS is to retard neurodegeneration, some patients may also experience symptomatic benefit due to its antidepressant effect. Such symptomatic benefit, if it occurs, will usually be noticeable within a couple days, 5-HTP is quick-acting unlike many antidepressants which take a couple weeks to kick in. WARNING: Don’t mix with other serotoninergic agents without first becoming informed regarding the dangers, please see the remarks about this in the discussion of dextromethorphan.
Roex Magnolia Extract 30 mg 90 capsules, item #85090, cost $15. Dosage: 2 to 4 caps a day, whatever seems to work best for you. Magnolia bark extract is usually regarded as an anti-anxiety therapeutic, but some patients experience improvement in bulbar and/or pseudobulbar symptoms as well. You’ll know quickly if you get symptomatic improvement. If you have problems with esophageal spasm or acid reflux, magnolia may also help with that as well. There’s reason to think that magnolia may also retard neurodegeneration, but the evidence for that is not sufficiently persuasive to recommend taking magnolia for that purpose alone.
LEF Peony Immune White Peony Root Extract 600 mg x 60 caps, standardized to 252 mg paeoniflorin. LEF #01811, cost $22. Dosing: one capsule per day. The primary purpose of the Peony is long-term (based primarily on heat shock protein activation), but some people may experience immediate symptomatic improvement in either or both upper and lower motor neuron symptoms due to its ion channel modulation characteristics. Peony is normally dosed together with licorice extract, which boosts its efficacy: see next item.
Nature's Answer Licorice root single herb supplement. (non-dgl), 450 mg x 90 capsules. LEF #28567, cost $6. Dosage: one cap per day. Licorice has a number of therapeutic actions: the one that matters to us is that it’s a co-factor with Peony root extract, even though licorice itself is not a heat shock protein inducer. The biochemical glycyrrhizin is responsible for this effect, the commonly available deglycyrrhized licorice extract won’t work. WARNING: Glycyrrhizin may raise blood pressure. If you have blood pressure issues, monitor blood pressure on a regular basis (several times a day at first) to make sure that licorice root isn’t causing problems. ALSO: licorice may be incompatible with ginseng (blood pressure issues again), which some people take but I have a low opinion of the stuff myself.
LEF CDP-Choline Caps, 250 mg x 60 caps. [CDP-choline is the same thing as citicoline.) LEF #01659, cost $25. Some patients report symptomatic benefit (improved energy, reduced brain fog). Appropriate dosing based on patient reports is probably two caps at a time. Unknown if it has any impact on neurodegenerative processes, although I suspect it does help a little.
What’s most important?
In the discussion above, I’ve grouped things in a certain way which emphasizes sequence in which to introduce things, assuming that within a couple weeks you’ll be doing most or all of it. There’s another approach, and that’s to begin with the stuff that’s probably most important. For your convenience, here’s a list of that kind. Unfortunately it’s mostly guesswork, but there is a little bit of science behind it.
- Only if you have bulbar/pseudobulbar symptoms, start with dextromethorphan. If you don’t see symptomatic improvement, it stops being important.
- Zinc gluconate.
- Magnesium taurate.
- NAC + selenium.
- Acetyl-L-carnitine (in this case ALC complex), + alpha lipoic acid (in this case R-lipoic).
- Vitamin B complex.
- Vitamin D + K.
- Only if you have bulbar, pseudobulbar, or upper motor neuron symptoms: magnolia bark extract. If you see no symptomatic benefit, it becomes unimportant.
- Vitamin E tocopherols and tocotrienols.
- Peony root extract + licorice root extract.
- Niacinamide + resveratrol.
- CoQ-10 (in this case ubiquinol).
- Milk thistle extract.
- Celery seed extract (3nB).
- CDP-choline. If you see symptomatic improvement (if so, it’ll probably be an increase in energy or a reduction in brain fog), continue. Unknown if it has any benefit other than symptomatic.
- Vitamin B-12.
Summary, grouped by therapeutic action
Anti-inflammatory Curcumin, 3nB, ibuprofen, Vitamin D, trimethylglycine
Glutathione support NAC, selenium, milk thistle extract, trimethylglycine
Mitochondrial support ALC, ALA, CoQ-10, some B-vitamins
Antioxidant ALA, CoQ-10, Vitamin E’s, some B-vitamins, plus anything in the category of “glutathione support”
Calcium channel modulator Magnesium, taurine, dextromethorphan, Peony root extract, trimethylglycine
Sodium and/or potassium ion transport modulator Peony root extract, possibly licorice
Serotonin agonist 5-HTP, dextromethorphan
Heat shock protein support Curcumin, Peony, Licorice
Heavy metal toxicity inhibitors Zinc, selenium, ALA.
Choline support CDP-choline
Immune modulator Vitamin D, zinc, iodine, anything having to do with glutathione support. Almost anything has some impact on the immune system.
END OF PROLETARIAT PROTOCOL DOCUMENT