Because components of the Wahls diet may affectinflammation, oxidative stress and mitochondrialdysfunction, it has plausible mechanisms for slow-ing ALS. Although a cross-sectional study suggeststhe intake of certain macro- and micronutrientsenriched in the Wahls diet was associated with bet-ter baseline motor function and lower risk for get-ting ALS, no case reports or clinical trials areshowing the Wahls diet affects disease progressionor survival in PALS. On the contrary, the clinicaltrial in MS patients showing significant weight lossand essential vitamin and mineral deficienciesraises serious concerns; two thirds of PALS alreadyexperience weight loss at the time of diagnosis,and weight loss is a strong predictive factor for fastdisease progression and shorter survival.Therefore, we cannot endorse the Wahls protocolfor slowing ALS progression.
Mechanistic plausibility - C
Insulin
Insulin treatment for ALS is an intriguing area for future research. However, the risks of insulin administration are significant and potentially lethal. Currently, there is no clinical evidence to support its use in PALS. Therefore, we cannot endorse insulin as a way to slow, stop, or reverse ALS progression at this time.
Vitamin C
Vitamin C is safe and inexpensive. As an antioxidant, it has a plausible mechanism for influencing the course of neurodegenerative diseases. Two flawed preclinical studies by the same group showed benefits in a mouse model of familial ALS. There are two case reports in which it was associated with improvement. However, there are multiple possible explanations for the improvement in these cases. It is not clear which if any dose of vitamin C might be beneficial for PALS; a small clinical trial using oral vitamin C at 2,000 mg daily was unable to demonstrate benefits in PALS. Based on this negative trial, we currently advise against using vitamin C to treat ALS.
Azathioprine
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
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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Basis
Basis has mechanisms of action that could theoretically be useful in treating ALS. It appeared reasonably safe in a small, short duration study of healthy volunteers and it is fairly inexpensive. However, we found no data in preclinical ALS models, no case reports, and no trials in PALS. Based on this lack of data, ALSUntangled cannot currently recommend use of Basis to slow, stop, or reverse the progression of ALS.
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