Can the Ketogenic Diet Lead to Alzheimer’s Disease?

The greatest medical fear of our century is not an infection, heart disease, or even cancer. It is Alzheimer’s disease, one of the most costly, insidious, and demoralizing conditions imaginable. It affects the individual, the family, and the community at their essence, at the level of the self. And it is threatening to overtake our healthcare system. Already, Alzheimer’s is one of the most expensive diseases, costing the nation well over $300 billion annually, and its cost is expected to rise to more than one trillion in the coming decades. ^[1] Its prevalence and mortality are also on track to rise substantially during the coming decades. It is one of the fastest-growing epidemics. ^[2]

We estimate that at least 90 percent of Alzheimer’s can be prevented and that the means to do so has been in plain sight. The same factors that affect the heart and other organs affect the brain. ^[3] This small organ, which constitutes 2% of our body weight but uses at least 20% of its energy, is very susceptible to vascular risk factors, inflammatory factors, and oxidative byproducts, all of which can be controlled by dietary lifestyle. ^[4] The brain’s capacity to grow and connect also gives it incredible restorative capacity. ^[5]

In our book The Alzheimer’s Solution, we reviewed and summarized over 300 peer-reviewed articles and brought our experience working in a comprehensive dementia clinic and conducting clinical research to bear on this question of what can help prevent cognitive decline and Alzheimer’s. What did we learn from all those sources? There is no question that a life filled with physical and mental activities, restorative sleep, stress management, and a whole food, plant-based diet low in sugar is profoundly effective for keeping our brains vibrant and active throughout a long life.

In addition to working in the clinic or the lab, we volunteer in underserved communities through our Healthy Minds Initiative. For us, Alzheimer’s disease is a battle for the soul and dignity of our aging society. So, when we hear information taken out of context, cherry-picked, or willfully misinterpreted to create a following or serve a particular agenda, we view it as an attack on all those communities we consider family.

This is why we are especially interested in unfounded claims about the ketogenic diet, which has recently become very trendy. Apart from the evidence for its efficacy as an adjunctive treatment for particular types of epilepsy, the ketogenic diet’s effect on cognitive health and the prevention of Alzheimer’s is unconvincing. ^[6]

The diet does temporarily affect brain cells by shifting away from glucose as the primary energy source; when the body’s preferred fuel source (glucose) is in short supply, the brain can instead use ketones. ^[7] But this shift can have long-term damaging effects. The path to achieving a ketogenic diet, which often leads to glucose and lipid dysregulation, has repeatedly been shown to create harmful byproducts, as well as deposition of amyloid and tau proteins, which are known to be strongly associated with end-stage Alzheimer’s disease.^[8]–[13]

The evidence could not be more disproportionate on the side of the whole food, plant-based diet. So, why do so many believe the ketogenic diet holds promise for combating Alzheimer’s disease? The diet’s popularity owes a lot to anecdotal appeals. The burden of proof should be on those presenting anecdotal evidence, but this is rarely demanded in the media and the general public discourse.

The dysregulation of fats and glucose metabolism, resulting in inflammation and immune dysregulation, ultimately leads to Alzheimer’s.^[14]–[17] The short-term ostensible gain in energy ends up costing the neurons dearly in the long run and most likely shortens lives. This cause is so important, and we need to empower communities in their fight for their mental health. There is no question that a whole food, plant-based diet helps maintain our most vital organ well into our 80s, 90s, and beyond.

References

1. Wong W. Economic burden of Alzheimer disease and managed care considerations. Am J Manag Care. 2020;26(8 Suppl):S177-S183. doi:10.37765/ajmc.2020.88482
2. Alzheimer’s Association. Alzheimer’s Disease Facts and Figures. Web page accessed September 24, 2024. https://www.alz.org/alzheimers-dementia/facts-figures
3. UNC Gillings School of Global Public Health. New study reveals strong connection between heart and brain health. Carolina Public Health. June 1, 2023. https://sph.unc.edu/sph-news/new-study-reveals-strong-connection-between-heart-and-brain-health/
4. Balasubramanian V. Brain power. Proc Natl Acad Sci U S A. 2021;118(32):e2107022118. doi:10.1073/pnas.2107022118
5. National Research Council (US) and Institute of Medicine (US) Committee on Integrating the Science of Early Childhood Development; Shonkoff JP, Phillips DA, editors. From Neurons to Neighborhoods: The Science of Early Childhood Development. Washington (DC): National Academies Press (US); 2000. 8, The Developing Brain. Available from: https://www.ncbi.nlm.nih.gov/books/NBK225562/
6. D’Andrea Meira I, Romão TT, Pires do Prado HJ, Krüger LT, Pires MEP, da Conceição PO. Ketogenic Diet and Epilepsy: What We Know So Far. Front Neurosci. 2019;13:5. Published 2019 Jan 29. doi:10.3389/fnins.2019.00005
7. National Center for Advancing Translational Sciences (NCATS). Ketogenic diet may offer a new approach to treating Alzheimer’s disease. March 22, 2022. https://ncats.nih.gov/news-events/news/ketogenic-diet-alzheimers
8. Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol. 2009;66(3):300-305. doi:10.1001/archneurol.2009.27
9. Granholm AC, Bimonte-Nelson HA, Moore AB, Nelson ME, Freeman LR, Sambamurti K. Effects of a saturated fat and high cholesterol diet on memory and hippocampal morphology in the middle-aged rat. J Alzheimers Dis. 2008;14(2):133-145. doi:10.3233/jad-2008-14202
10. Bayer-Carter JL, Green PS, Montine TJ, et al. Diet intervention and cerebrospinal fluid biomarkers in amnestic mild cognitive impairment. Arch Neurol. 2011;68(6):743-752. doi:10.1001/archneurol.2011.125
11. Morris MC, Evans DA, Bienias JL, et al. Dietary Fats and the Risk of Incident Alzheimer Disease. Arch Neurol.2003;60(2):194–200. doi:10.1001/archneur.60.2.194
12. Kalmijn S, Launer LJ, Ott A, Witteman JC, Hofman A, Breteler MM. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol. 1997;42(5):776-782. doi:10.1002/ana.410420514
13. Li L, Cao D, Garber DW, Kim H, Fukuchi K. Association of aortic atherosclerosis with cerebral beta-amyloidosis and learning deficits in a mouse model of Alzheimer’s disease. Am J Pathol. 2003;163(6):2155-2164. doi:10.1016/s0002-9440(10)63572-9
14. Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388-405. doi:10.1016/S1474-4422(15)70016-5
15. Takechi R, Galloway S, Pallebage-Gamarallage MM, Lam V, Mamo JC. Dietary fats, cerebrovasculature integrity and Alzheimer’s disease risk. Prog Lipid Res. 2010;49(2):159-170. doi:10.1016/j.plipres.2009.10.004
16. Azevedo de Lima P, Baldini Prudêncio M, Murakami DK, Pereira de Brito Sampaio L, Figueiredo Neto AM, Teixeira Damasceno NR. Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy. Nutrition. 2017;33:271-277. doi:10.1016/j.nut.2016.06.016
17. Lima PA, de Brito Sampaio LP, Damasceno NR. Ketogenic diet in epileptic children: impact on lipoproteins and oxidative stress. Nutr Neurosci. 2015;18(8):337-344. doi:10.1179/1476830515Y.0000000036