As of July 2023 we found no new information that would warrant any TOE grade changes
Since our initial review, the ingredients in the Deanna Protocol (DP) appear to have changed. According to the product’s website (which now sells a one-month supply of it for $135.99 ), the current ingredients are Alpha Ketoglutaric Acid, L-arginine, and GABA. The rationale for this change is unclear. It does not change our Mechanisms grade. The mSOD1 mouse study we mentioned in our review has been published (PLoS One. 2014; 9(7): e103526). This study shows that treatment with some of the ingredients in a former version of the DP was associated with slowed progression and improved survival. Flaws in this study include lack of rater blinding and treatment initiation prior to symptom onset (not possible in patients). A newer publication (Int J Pharm Pharm Res. 2017 Dec; 11(1): 348–374) reported that one (but not another) version of DP could reduce a measure of stress in motor neurons from patients with familial ALS caused by SOD1 mutations and also in iPSC-derived-motor-neurons from patients with sporadic ALS that were treated with glutamate. It is not clear whether the raters in this study were blinded to treatment assignment. It is also unclear how relevant these cell models are to humans with ALS. Thus, neither of these new publications change our Pre-Clinical Grade of C. The DP website continues to report anecdotal evidence of benefit, but we have not been able to validate the diagnoses or reported benefits in any of these patients. Thus, our Cases grade remains D. We found no human trials of DP in patients with ALS so our trials grade is unchanged. We found no new reports of side effects, so our Risks grade remains B. Our conclusion remains unchanged: we cannot recommend DP as an ALS treatment. We hope to see a well-designed pilot trial in people living with ALS in the future.
Key Information
Mitochondrial dysfunction, glutamate excitotoxicity, and oxidative stress have all been implicated in ALS pathogenesis, and targeting these mechanisms individually or by a cocktail such as the Deanna Protocol could play a role in future ALS therapies. However, many of the preclinical and animal studies related to these pathways have not translated into successful treatments in patients with ALS. While there are anecdotal reports of improvements in patients with ALS on the Deanna Protocol, there is no convincing objective evidence of benefit yet. Thus, at this time, ALSUntangled does not recommend the Deanna Protocol to patients with ALS.
Before it can be recommended, a reproducible version of the Deanna Protocol should be shown to influence plausible physiologic mechanisms such as central nervous system ketone bodies, as well as clinically meaningful outcome measures such as ALSFRS-R and FVC in patients with ALS.