How this Diet is Rewiring Aging Brains

Lifestyle Strategies in the Absence of a Cure

Despite decades of research, Alzheimer’s disease remains without a definitive cure. In response, scientists are increasingly turning to lifestyle-based interventions that may help delay or mitigate its progression. One such avenue under examination is the ketogenic diet, which targets brain energy metabolism—a key aspect believed to be impaired in Alzheimer’s patients.

Energy Demands and Brain Metabolism

The brain requires a substantial amount of energy, typically derived from glucose. However, in the absence of adequate glucose, it can utilize ketones. Prior research has shown that brains affected by mild cognitive impairment and Alzheimer’s disease are able to absorb ketones more effectively than glucose. According to the authors, “prolonged brain energy shortage leads to neuronal death, impaired amyloid-β and tau protein clearance, and the development of Alzheimer’s disease.” This makes restoring energy balance in the brain a promising therapeutic strategy.

Evaluating the Evidence Across Clinical Trials

The authors systematically evaluated randomized controlled trials to assess the effects of ketogenic diets on Alzheimer’s disease. Ten trials conducted across the United States, Japan, Canada, China, and New Zealand were included, comprising a total of 691 Alzheimer’s patients. After accounting for 40 dropouts, 651 participants were analyzed. The interventions spanned from 12 to 60 weeks.

The dietary interventions varied. One trial implemented a standard ketogenic diet with macronutrients distributed as 58% fat, 29% protein, 7% fiber, and 6% net carbohydrates by weight. Eight trials employed the medium-chain triglyceride (MCT) diet, which uses lab-produced fats that more readily generate ketones. One trial used the modified Atkins diet (MAD).

Cognitive function was assessed using diverse testing scales, including the Mini-Mental State Examination (MMSE), the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-Cog), the Nishimura Mental State Scale (NM scale), and the Activities of Daily Living (ADL) scale. The MMSE is a common screening tool for cognitive disorders, ADAS-Cog evaluates memory, and the NM scale measures functional ability. The consistent results across different tests strengthened the credibility of the findings.

The meta-analysis showed that ketogenic diets led to statistically significant cognitive improvements as measured by MMSE, ADAS-Cog, and NM scale. No significant changes were found using the ADL scale.

Biochemical Implications of the Ketogenic Diet

Four studies also assessed lipid profiles. The ketogenic diet was associated with increased levels of triglycerides and low-density lipoprotein cholesterol (LDL-C), commonly referred to as “bad” cholesterol. However, there were no significant changes in total cholesterol or high-density lipoprotein cholesterol (HDL-C), the so-called “good” cholesterol.

Adverse Effects and Long-Term Considerations

Despite the cognitive improvements, the ketogenic diet is not without risks. The studies reviewed were relatively short, generally lasting only a few months, which limits conclusions about long-term safety. Adherence to the diet may also pose challenges, as indicated by some participants withdrawing during the studies.

Potential side effects of a strict ketogenic diet include constipation, fatigue, headache, nausea, and hypoglycemia. More serious complications such as dehydration, hepatitis, pancreatitis, electrolyte disturbances, reduced bone mineral density, kidney stones, cardiac issues, and anemia have also been reported. The observed increases in LDL-C and triglycerides may raise the risk of cardiovascular disease.

Methodological Limitations

This review is based on secondary data from trials that were not conducted under uniform conditions. Variations in diet protocols and study durations complicate interpretation. Additionally, some trials included small sample sizes.

Nonetheless, the findings provide promising evidence supporting the ketogenic diet’s role in improving cognitive function in Alzheimer’s disease patients, while also underscoring the importance of weighing potential risks. The authors conclude that “future research could explore optimizing KD formulations and intervention strategies to maximize cognitive improvements while minimizing associated health risks.”

Your Call to Action for Cognitive Health and Alzheimer’s Prevention

If you or a loved one is concerned about Alzheimer’s disease, consider discussing ketogenic dietary options with a qualified healthcare provider. While this diet shows promise in supporting brain energy metabolism and cognitive performance, it is essential to personalize any nutritional intervention based on individual health status and risks. To safely explore this strategy, seek guidance on how to implement a ketogenic diet under medical supervision, monitor lipid levels, and ensure nutritional adequacy.

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Study Links:

Rong, L., Peng, Y., Shen, Q., Chen, K., Fang, B., & Li, W. (2024). Effects of ketogenic diet on cognitive function of patients with Alzheimer’s disease: a systematic review and meta-analysis. The journal of nutrition, health & aging, 28(8), 100306.

Nugent, S., Croteau, E., Pifferi, F., Fortier, M., Tremblay, S., Turcotte, E., & Cunnane, S. C. (2011). Brain and systemic glucose metabolism in the healthy elderly following fish oil supplementation. Prostaglandins, leukotrienes, and essential fatty acids, 85(5), 287–291.

Croteau, E., Castellano, C. A., Fortier, M., Bocti, C., Fulop, T., Paquet, N., & Cunnane, S. C. (2018). A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease. Experimental gerontology, 107, 18–26.

Zhang, S., Lachance, B. B., Mattson, M. P., & Jia, X. (2021). Glucose metabolic crosstalk and regulation in brain function and diseases. Progress in neurobiology, 204, 102089.

Dashti, H. M., Mathew, T. C., & Al-Zaid, N. S. (2021). Efficacy of Low-Carbohydrate Ketogenic Diet in the Treatment of Type 2 Diabetes. Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 30(3), 223–235.

Roehl, K., & Sewak, S. L. (2017). Practice Paper of the Academy of Nutrition and Dietetics: Classic and Modified Ketogenic Diets for Treatment of Epilepsy. Journal of the Academy of Nutrition and Dietetics, 117(8), 1279–1292.

Włodarek D. (2019). Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer’s Disease and Parkinson’s Disease). Nutrients, 11(1), 169.

Crosby, L., Davis, B., Joshi, S., Jardine, M., Paul, J., Neola, M., & Barnard, N. D. (2021). Ketogenic Diets and Chronic Disease: Weighing the Benefits Against the Risks. Frontiers in nutrition, 8, 702802.