Zinc has plausible mechanisms for modulating ALS progression, specifically with its roles in oxidative stress reduction and stabilization of SOD1 structure and function. Preclinical data has demonstrated potential benefits in slowing ALS progression at moderate doses in mouse models, but high doses without additional supplementation of copper were shown to be harmful. Clinical data on zinc supplementation in PALS is limited, but numerous case reports and a small pilot trial provide some insight. The case reports indicated no benefit from zinc supplementation, while the pilot trial reported potential benefits in slowing ALS progression. However, this trial lacked statistical analyses and had a very small sample size, which significantly limits the strength of its findings. Based on the current lack of substantial clinical evidence supporting the potential benefits of zinc supplementation in PALS, we cannot endorse zinc supplementation as a treatment for ALS at this time.
Patient case reports
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.
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.
Rituximab
ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS who ask about them. Here we review rituximab, a drug which specifically depletes B lymphocytes. We show a current lack of evidence for a role of these cells in ALS progression. The one patient we found who described using Rituximab for their ALS found no benefit. Given all this, and the known serious risks of rituximab, we advise against its use as an ALS treatment.
You can read it here
https://www.tandfonline.com/doi/full/10.1080/21678421.2022.2122845?src=
L-Carnitine
There are good theoretical mechanisms for carnitines, some pre-clinical evidence for
LC and ALCAR, and a single clinical trial that suggested ALCAR could slow disease progression in PALS. All three carnitines appear to be well-tolerated, generally safe, and inexpensive. We believe that there is a need for future clinical trials of carnitines in PALS to further elucidate their efficacy. Until there is further data, we cannot endorse any of these supplements as a definite way to slow ALS progression; however, oral ALCAR at 1000mg three times daily (3000 mg total daily dose) appears to be a theoretically promising supplement available for PALS whom would like to self-experiment.
Copper
Copper dysregulation may play a role in ALS progression, particularly for the form caused by SOD1 mutations. Given the complexity of this problem, simple copper supplements are unlikely to be useful to PALS with normal serum copper levels. We do not recommend using these. CuATSM, on the other hand, has more promising potential mechanisms of action, and several positive pre-clinical studies in mutant SOD1 ALS models. There are even a small number of PALS reporting benefits from it, though in our opinion the described benefits are thus far of uncertain clinical significance. At this time, the safety of repeated doses of CuATSM is unknown, as is the optimum daily dose, and it appears to be very expensive. Until trials clarify dosing and safety, as well as effectiveness in patients with and without SOD1 mutations, we do not recommend using CuATSM for ALS.
Click here to download the complete review.
Acuscope
Acuscope appears reasonably safe, but it is not clear that it has a mechanism of action that would be useful to PALS. One person with PLS experienced slightly slower ALSFRS-R measurements while using Acuscope than she did before starting it, but a PALS had slightly faster ALSFRS-R progression during treatment. Since the natural history of motor neuron disease progression can vary spontaneously, it is not clear that either of these slight changes in progression were related to the treatment. Given these limitations, at this time we cannot endorse the use of Acuscope to slow, stop or reverse ALS progression.
Click here to download the complete review.
Vitamin D
At this time, there is evidence that PALS, like those with other chronic illnesses, are at increased risk for vitamin D deficiency. It is, therefore, reasonable to screen PALS for this. If vitamin D deficiency is found, it seems reasonable to supplement vitamin D according to established guidelines (31) in order to avoid medical complications of vitamin D deficiency. It is not yet clear, however, that vitamin D supplementation can slow disease progression, improve muscle strength, or reduce falls in PALS. We support further studies to answer these questions.