ALA has several plausible mechanisms for slowingALS progression, including enhancing energy pro-duction, reducing oxidative stress as a potent anti-oxidant and anti-inflammation. Preclinical studiesdemonstrated better motor function and improvedsurvival. One open-label study suggested improvedQOL and fatigue when administered as a palla-dium lipoic acid complex, but motor function wasnot assessed. Several PALS in the ALS online community reported improved muscle strengthwhen taking ALA as part of extensive supplementregimens, but most did not. Therefore, it isunclear whether the reported improvement wasdirectly related to ALA. Although one clinical trialwas completed in PALS, the result has not beenpublished. ALA was safe and well-tolerated basedon self-report from PALS and in clinical trials forother disease conditions at 600 mg daily. Given theabove, we cannot endorse ALA as an effectivetherapy for PALS. We support more research onthe efficacy of ALA in slowing ALS progression.
Patient trials
Psilocybin
Psilocybin may be able to influence ALS-relevant mechanisms including neuroinflammation and brain glutamate levels, but this ability has not yet been demonstrated in ALS models or in PALS.There have been no studies of psilocybin in ALS relevant preclinical models, and no case reports documenting the effects of psilocybin on ALS progression. Given the potential for serious side effects, we do not currently support the use of psilocybin to slow ALS progression.
WAHLS Protocol
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.
PoNS Device
Considering the fact that electrical stimulation was first used as a medical treatment more than 100 years ago (30), and first used as an ALS treatment 30 years ago (31), it is disappointing that we have yet to find a clear way to use this to help PALS. PoNS™ is a newer version of this. There is a vague theoretical mechanism (neuromodulation) by which PoNS™ could potentially modulate neuroplasticity in the brainstem and cortex, but whether it provides any beneficial or deleterious effects on ALS progression is currently unknown. While there are early, promising data showing that the PoNS™ device improving gait in patients with multiple sclerosis, this may not translate to PALS. There are no pre-clinical data or clinical trials of PoNS™ therapy in PALS to determine efficacy. The PoNS™ device appears to be relatively safe but its substantial cost and prescription-only status will limit accessibility for PALS. Given the current lack of ALS-relevant data, we cannot currently support the use of PoNS™ therapy to slow, stop, or reverse ALS progression. We hope that this review of PoNS™ and the broader topic of neurostimulation spurs future research toward helping PALS.
Ashwagandha
WS appears reasonably safe, has plausible mechanisms by which it might slow ALS progression, and has promising data obtained in multiple different clinical models of ALS. While there are also some interesting self-reports from PALS and one verified ALS reversal on a compound containing WS, these must be interpreted with caution because of the variable natural history of ALS progression. We conclude that WS is a reasonable compound for ALS trials, and we look forward to the results of the one trial that is underway.
Lions Mane
While Lion’s Mane may have neuroprotective, neurotrophic, antioxidant, and anti-inflammatory properties that could, at least in theory, potentially help ALS, there are still no studies in ALS-relevant cell or animal models, nor in humans with ALS. Therefore, we do not have enough information to support the current use of Lion’s Mane for treating ALS. We hope to see the validation of its neuroprotective and anti-inflammatory benefits in ALS disease models, which may ultimately lead to clinical trials in PALS.
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.
Caffeine
Caffeine is inexpensive, reasonably safe at doses of under 400 mg daily, and has plausible mechanisms by which it could slow ALS progression. However, data from pre-clinical models are contradictory and a two cohort studies showed no clear relationship between caffeine intake and ALS progression. Based on all this, we cannot endorse caffeine as anALS treatment.