The Wahls diet is a modified Paleolithic diet that emphasizes dark green leafy vegetables, colorful fruits, high-quality animal proteins, and omega-3 polyunsaturated fatty acids, while limiting grains, legumes, dairy products, sugar, and processed foods containing proinflammatory omega-6 fatty acids. The Wahls diet may reduce inflammation, oxidative stress, and mitochondrial dysfunction and has plausible mechanisms for slowing amyotrophic lateral sclerosis (ALS) progression. However, research on its dietary components in the ALS animal models has yielded conflicting results. Though multiple cohort studies suggest high carotenoids, omega-3 fatty acids and fruit intake are associated with reduced ALS risks, neither the diet nor its components has been demonstrated to slow down ALS progression in case studies or clinical trials. On the contrary, the Wahls diet, a restrictive, low-carbohydrate and low glycemic index diet, caused an average weight loss of 7.2% BMI in multiple sclerosis clinical trials, which is a significant concern for people living with amyotrophic lateral sclerosis (PALS) as weight loss is associated with faster ALS progression and shorter survival. Considering the above, we cannot endorse the Wahls diet for slowing ALS progression.

ALSUntangled reviews alternative and off-label treatments for people with amyotrophic lateral sclerosis (PALS). Here we review glucocorticoids. Neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis, so some hypothesize that glucocorticoids might be an effective ALS therapy through their immunosuppressive effects. In this paper, we review the available evidence for glucocorticoids in ALS, including one pre-clinical study with a genetic mouse model of ALS, nine case reports (ranging from 1 to 26 patients each), and four clinical trials. We also review the possible side effects (including steroid myopathy) and the costs of therapy. We graded the level of evidence as follows: Mechanism, D; Pre-Clinical, F; Cases, B; Trials, F; Risks, C. Our review of the current evidence concludes that glucocorticoids do not offer clinical benefit in ALS and confer serious risks. Thus, ALSUntangled does not recommend glucocorticoids as a treatment for ALS.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review astaxanthin which has plausible mechanisms for slowing ALS progression including antioxidant, anti-inflammatory, and anti-apoptotic effects. While there are no ALS-specific pre-clinical studies, one verified "ALS reversal" occurred in a person using a combination of alternative therapies which included astaxanthin. There have been no trials of astaxanthin in people living with ALS. Natural astaxanthin appears to be safe and inexpensive. Based on the above information, we support further pre-clinical and/or clinical trials of astaxanthin in disease models and PALS, respectively, to further elucidate efficacy.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here, we review caffeine which has plausible mechanisms for slowing ALS progression. However, pre-clinical studies are contradictory, and a large case series showed no relationship between caffeine intake and ALS progression rate. While low doses of caffeine are safe and inexpensive, higher doses can cause serious side effects. At this time, we cannot endorse caffeine as a treatment to slow ALS progression.

Lion's Mane (Hericium erinaceus) has historically been used as traditional medicine in Asia and Europe for its potential benefits in fighting infection and cancer. It has gained interest in the neurodegenerative disease field because of its mechanisms of action; these include anti-inflammation, neuroprotection, and promoting neurite growth demonstrated in various cell and animal models. A very small, double-blind, placebo-controlled trial in patients with mild cognitive impairment showed a temporary improvement in cognitive function; this finding has yet to be replicated. However, there have been no studies in ALS cell or animal models or in humans with ALS. Lion's Mane appears safe and inexpensive when consumed in powder or capsule, but one anaphylactic case was reported after a patient consumed fresh Lion's Mane mushroom. Currently, we do not have enough information to support the use of Lion's Mane for treating ALS. We support further research in ALS disease models and clinical trials to study its efficacy.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review ozone therapy. Ozone therapy has possible mechanisms for slowing ALS progression based on its antioxidant, anti-inflammatory, and mitochondrial effects. A non-peer-reviewed report suggests that ozone treatment may slow progression in a mTDP-43 mouse model of ALS. One verified "ALS reversal " occurred on a cocktail of alternative treatments including ozone. There are no ALS trials using ozone to treat PALS. There can be potentially serious side effects associated with ozone therapy, depending on the dose. Based on the above information, we support an investigation of ozone therapy in ALS cell or animal models but cannot yet recommend it as a treatment in PALS.

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.

Vinpocetine (chemical name 14-ethoxycarbonyl(3a,16a-ethyl)-14,15-eburnamine) is a product derived from an alkaloid substance in the periwinkle plant Vinca minor (2). In many countries it is classified as a prescription drug and is used for the treatment of acute stroke and cognitive impairment (3), although systematic reviews have failed to confirm any benefits for patients with these conditions (4,5). In the Unites States, it is classified as a nutritional supplement (3). At least one website claims that Vinpocetine might be “beneficial for ALS” (6). A published case series demonstrated that Vinpocetine was associated with reduced cramping in PALS and suggested further study, including determining whether it could slow ALS progression (7). This review examines Vinpocetine’s potential role in slowing ALS progression.

ALSUntangled reviews alternative and off label treatments with a goal of helping patients make more informed decisions about them. Here we review ketogenic diets. We shows that these have plausible mechanisms, including augmenting cellular energy balance and reducing excitotoxicity, neuroinflammation and oxidative stress. We review a mouse model study, anecdotal reports and trials in ALS and other diseases. We conclude that there is yet not enough data to recommend ketogenic diets for patients with ALS, especially in light of the many side effects these can have.