As an immunosuppressant drug, AZA has a plausible mechanism for slowing the progression of ALS. However, there is no pre-clinical data to support its use and two clinical trials did not support efficacy. There are 2 published cases in which
ALS reversals occurred on AZA, but it is not clear to us that the AZA actually contributed to the ALS improvements. One of these patients also had myasthenia gravis, which is known to cause reversible weakness and therefore complicates the measurement of ALS. The other patient was taking many different medications and supplements along with AZA. AZA has very serious, potentially fatal, both short and long-term risks associated with its use and requires medical monitoring. Based on the
available data, we do not advise the use of AZA as an ALS treatment
Mechanistic plausibility - C
LEAP2BFIT
Many ingredients contained within LEAP2BFIT could, at least in theory, be beneficial in ALS. Some of these ingredients have supporting animal or human studies. However, it is unknown if these ingredients are being provided in therapeutic quantities since the dosages are not disclosed. Furthermore, it is impossible to know the net positive or negative effect of so many ingredients without carefully testing the combination. Based on the above discussions, we do not currently recommend LEAP2BFIT as a way to slow, stop, or reverse ALS.
Glutathione
As an ALS treatment, glutathione and cysteine-containing supplements that increase glutathione appear reasonably safe, and they have a plausible mechanism, positive preclinical data and 2 interesting case reports. Unfortunately small clinical trials of glutathione itself and of acetylcysteine showed no significant benefit. Given these negative clinical trials, we do not advise PALS to take glutathione or cysteine-containing supplements for their ALS at this time.
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Curcumin
Oral curcumin is safe, inexpensive, and has at least four potential mechanisms by which it might theoretically be useful in treating PALS. Flawed preclinical studies showed benefits of a curcumin chemical analog in a cell model of ALS, three PALS experienced validated motor improvements on regimens including curcumin (although there are several alternative explanations for these improvements) and there is one small pilot trial showing some benefit of curcumin in PALS. Based on the evidence presented in this review, some of us are planning a trial of Theracurmin at 90 mg twice daily in PALS.
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Ayahuasca
Ayahuasca has interesting mechanisms that could potentially be useful in treating human ALS. We found one person who appears to have experienced an ALS reversal following exposure to a single dose of ayahuasca and several other AOTs. We do not believe that a single dose of ayahuasca could trigger a mechanism that would reverse ALS. There are more plausible explanations for this case, including an unrecognised ALS mimic syndrome. Importantly, there are several documented harms associated with ayahuasca use, including hospitalisation, intubation, and death. There are also serious theoretical risks, including hypertensive crisis, serotonin syndrome, and birth defects. Given this information, at this time, we do not endorse the use of ayahuasca to slow, stop or reverse ALS progression.
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Inosine
Inosine is a low-cost supplement that increases the levels of urate, a naturally occurring antioxidant. With appropriate blood and urine monitoring, it appears reasonably safe. Epidemiologic data suggest that high urate levels may be associated with improved survival in ALS, which prompted preclinical studies and clinical trials of inosine. These are still ongoing and will help determine whether inosine could be a useful treatment for ALS.
Declaration of interest: ALSUntangled is sponsored by the ALS Association and the Motor Neurone Disease Association.
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Gluten-Free Diet
Theoretically, gluten-induced autoimmunity could trigger ALS. However, the data supporting this link are weak, consisting of two association studies and a single case-report. Further studies are needed to confirm the relationship between GRDs and ALS, and the utility of the GFD in patients with both conditions. In spite of the fact that GFD is reasonably safe, it is a complex undertaking and is more expensive than a standard diet. While we wait for better data, it would be reasonable to screen PALS who have GI symptoms, iron-deficiency anemia, or an abnormal brain MRI for the antibodies associated with GFDs. Those with elevated antibodies could be referred to a gastroenterologist for further work-up, and if this is consistent with a GRD, then GFD could be tried under the guidance and monitoring of a dietician.
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Lunasin
Lunasin has interesting mechanisms of action that might be useful in treating ALS, and it appears reasonably safe although some forms of it are expensive. While some PALS have reported improvements on lunasin, we have thus far found only one in which we were able to independently validate these improvements. This patient had atypical features for ALS including a history of myasthenia gravis, which can produce weakness that improves spontaneously. At this time there is not enough evidence to recommend that PALS take lunasin. A reasonable next step would be a small pilot trial of lunasin with validated ALS diagnoses and outcome measures.
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