Patients often ask me about specialized diets, supplements, vitamins and other alternative approaches to treating memory problems, so I thought we should review the science about a few that we’ve been asked about lately. I asked Carolyn Akers, a Vanderbilt Neuroscience major, to dig into the evidence behind the Ketoflex diet, Beta-XB supplement and Prevagen — here’s what she found:
Ketoflex
Dr. Dale Bredesen of UCLA describes the Ketoflex diet as a non-drug therapy that “reverses” cognitive decline in Alzheimer’s disease (AD). Limiting carbohydrate and calorie consumption induces a “mildly ketogenic state,” in which ketone bodies (e.g. acetoacetate) are metabolized as an alternative energy source over glucose. The Bredesen Protocol claims that this alternative pathway yields more energy in the form of ATP.[i]
Ketogenic diets have already shown efficacy as therapies in severe epilepsy.[ii] On the other hand, hyperketonemia and acidosis have been identified as risks for Type 1 diabetics on ketogenic diets. A growing body of literature suggests that, since metabolic dysregulation has been implicated in AD, fasting and/or ketogenesis may have neuroprotective effects in mouse and rat models.[iii] However, there is little evidence to support efficacy in slowing — let alone reversing — cognitive decline in human AD cases. A 2016 study conducted by Bredesen et al. showed “moderate to dramatic improvements” in 11 AD patients’ neuropsychological testing after 5-24 months of following Bredesen’s diet plan[iv]; however, its journal of publication, Aging, is of dubious reputation and was listed in librarian Jeffrey Beall’s compilation of predatory journals and publishers.[v]
The diet plan is part of the Bredesen Protocol, a “comprehensive, personalized program” heavily advertised to be capable of reversing cognitive decline. The program cost consumers a steep one-time payment of $4,000-20,000 in a New Zealand program.[vi]
Beta-XB
Dr. Fred Pescatore advertises the beta-XB supplement as a “brain-healing miracle” that restores cognitive function by “energizing” mitochondria. The product website claims that brain cells already use beta-XB to synthesize ATP, and that the cognitive decline associated with AD is a result of an “energy crisis” due to beta-XB deficiency.[vii]
Aside from references to plant extracts, the site does not further specify what the supplement actually contains.[viii] Anecdotal evidence of dramatic symptom reversal is not corroborated by any studies. The studies listed on the product website do not examine the effects of a specific “beta-XB” drug, but rather the impact of oral ketogenic compounds such as beta-hydroxybutyrate on neurodegeneration.[ix]
Beta-XB is included in a memory supplement package priced at $189.
Prevagen
Manufactured by Quincy Bioscience, Prevagen contains apoaequorin, a calcium- and cholesterol-binding protein found in jellyfish. Apoaequorin intake has been shown to protect rat hippocampal neurons from glucose deprivation.[x] A company-published study of 218 adults with self-reported memory issues reported improvements in verbal memory and executive function in the treatment group after 90 days of taking 10 mg apoaequorin.[xi]
Apoaequorin’s mechanism of action remains to be studied. It is dubious as to whether the ingested protein can retain its structure and function during digestion, then pass through the blood brain barrier to reach its neuronal targets. Apoaequorin’s efficacy as a “memory supplement” has not been confirmed in any peer-reviewed publications. In 2017, the FTC charged Quincy Bioscience with fraud for falsely advertising the supplement as a memory booster.[xii] Several online patient communities have reported headaches, nausea, and severe hypertension as adverse effects of taking apoaequorin supplements.[xiii]
Prevagen’s listed price is about $60.
After reviewing these findings, I would advise my patients against using any of the treatments. The most effective “natural” ways to enhance memory is to make sure you get high-quality sleep, eat a diet rich in fruits and vegetables to make sure you are getting plenty of antioxidants and stay physically, mentally and socially active.
References
[i] https://drlonsdorf.com/pdf/ReCODE-Report-MPI-Cognition-NUTRITIONAL-GUIDELINES.pdf ]
[ii] A. van Berkel, D. IJff, J. M. Verkuyl. Cognitive benefits of the ketogenic diet in patients with epilepsy: A systematic overview. Epilepsy & Behavior, 87 (2018), pp. 69-77, https://doi.org/10.1016/j.yebeh.2018.06.004.
[iii] A. Paoli, A. Bianco, E. Damiani, G. Bosco. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases. BioMed Research International, 2014 (2014), pp. 10, https://doi.org/10.1155/2014/474296.
[iv] D. Bredesen, E. Amos, J. Canick, M. Ackerley, C. Raji, M. Fiala, J. Ahdidan. Reversal of cognitive decline in Alzheimer’s disease. Aging, 8 (2016), pp. 1250-1258, https://dx.doi.org/10.18632%2Faging.100981.
[v] https://beallslist.weebly.com
[vii] http://betaxb.com
[viii] https://pro.ovhlearning.com/p/OV3SFPA1A/WOV3TC02/?h=true
[ix] H. White, K. Venkatesh, B. Venkatesh. Systematic Review of the Use of Ketones in the Management of Acute and Chronic Neurological Disorders. Journal of Neurology and Neuroscience 8 (2018), https://dx.doi.org/10.21767/2171-6625.1000188
[x] J. Detert, E. Adams, J. Lescher, J-A Lyons, J. Moyer Jr. Pretreatment with Apoaequorin Protects Hippocampal CA1 Neurons from Oxygen-Glucose Deprivation. PLOS ONE 8 (2013), https://doi.org/10.1371/journal.pone.0079002.
[xi] K. Lerner et al. Madison Memory Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of Apoaequorin in Community-Dwelling, Older Adults. Quincy Bioscience, LLC (2016), https://www.prevagen.com/wp-content/uploads/2017/02/ClinicalTrialSynopsis-cmk816.pdf.
[xiii] The ALSUntangled Group. Apoaequorin (Prevagen). Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 14 (2013), pp. 78-79, https://doi.org/10.3109/17482968.2012.727302.