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.
Mechanistic plausibility
Vitamin E
Vitamin E (a-tocopherol) is perhaps the most studied supplement in the history of ALS and was taken by one of the most famous ALS patients. Vitamin E has mechanistic potential in ALS as an antioxidant but appears in the SOD1 mutant mouse model to only have an effect on delaying disease onset. This bears out in human populations as large prospective cohorts show that long-duration vitamin E supplementation may decrease the risk of ALS, but randomized clinical trials show that even high dose vitamin E does not benefit the disease once ALS has been diagnosed. Although it is inexpensive and safe, we do not recommend vitamin E to slow, stop or reverse ALS
based on the lack of efficacy in clinical trials.
Vinpocetine
Vinpocetine has several plausible mechanisms by which it could slow ALS progression. There are two PALS online who reported improved motor functions on supplement cocktails containing Vinpocetine, but many other PALS have had no
benefits. Serious side effects from Vinpocetine are rare and it is inexpensive. We support further study of Vinpocetine in ALS, but our group was split on what the next step should be; some were in favor of a study in a pre-clinical ALS model and others were in favor of a small human trial to confirm its benefit on cramps (7) and to explore whether it is safe, tolerable and might slow disease progression.
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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Methylcobalamin
MeCbl has promising mechanisms and positive preclinical data from two different ALS models. Unfortunately, the anecdotal data we found did not identify any clear specific benefit, and the best of three clinical trials was unable to show an overall difference in ALSFRS-R progression or survival between PALS treated with MeCbl and those treated with placebo (26). A sub-group of patients with very specific pretreatment progression rates of 1–3 ALSFRS-R points over 12 weeks, and very early disease (less than 12 months from symptom onset) may have had benefit (26). This finding needs to be replicated, especially since an earlier study suggested patients with longer disease duration were more likely to benefit (20). We would like to see a full traditional sub-group analysis (28) carried out on the data from the third trial (26). This sub-group analysis could then be used to design inclusion criteria for a new phase III trial comparing MeCbl 50 mg twice a week IM to placebo. The new trial could measure serum B12 and homocysteine, and have pre-planned sub-group analyses that are both logical and practical. While we wait for this, PALS who wish to try MeCbl are reminded that the above studies used very high, injected doses, which appear to be available only by prescription. Lower over-the-counter doses administered orally have not been studied. It is well established that over-the-counter oral supplements may be of poor and inconsistent quality (32). Some over-the-counter oral vitamin B supplements contain not only B12 but also B6, which in large quantities can be harmful to the nervous system (33).
Sodium Chlorite WF10
The NP001 formulation of sodium chlorite acts through a plausible mechanism and preliminary data suggest that it is safe and may slow ALS progression in some PALS. The WF10 formulation of SC appears to act through this same mechanism. Although WF10 is available for off-label use, it is very expensive, may have more side-effects than NP001, and at this time has only scant anecdotal evidence for efficacy in PALS. ALSUntangled supports further carefully monitored studies of NP001 and WF10 in PALS. In contrast, oral sodium chlorite has potentially dangerous and toxic side-effects may hasten disease progression, and is not clearly absorbed from the gut. We do not recommend further use of oral sodium chlorite unless it can at least be shown to be safe and to act on mechanisms in humans that are relevant to ALS.
Sodium Chlorite NP001
The NP001 formulation of sodium chlorite acts through a plausible mechanism and preliminary data suggest that it is safe and may slow ALS progression in some PALS. The WF10 formulation of SC appears to act through this same mechanism. Although WF10 is available for off-label use, it is very expensive, may have more side-effects than NP001, and at this time has only scant anecdotal evidence for efficacy in PALS. ALSUntangled supports further carefully monitored studies of NP001 and WF10 in PALS. In contrast, oral sodium chlorite has potentially dangerous and toxic side-effects may hasten disease progression, and is not clearly absorbed from the gut. We do not recommend further use of oral sodium chlorite unless it can at least be shown to be safe and to act on mechanisms in humans that are relevant to ALS.