The results of 10 independently conducted clinical trials suggest that ketogenic diets have a positive impact on the cognitive function of Alzheimer’s disease patients [1].
Keto instead of a pill?
Despite extensive research, there is stilll no effective treatment for Alzheimer’s disease. Therefore, approaches that aim to delay disease through lifestyle changes, such as diet, are being investigated.
One of the possible therapeutic targets is brain energy metabolism. The authors of this article focused specifically on this metabolism and the impact of ketogenic diets on Alzheimer’s disease.
High energy demands
The brain has high energy needs. Under normal conditions, it consumes glucose, but when glucose levels are low, the brain can use ketones as an energy source. Previous studies have found that in patients with mild cognitive impairment and Alzheimer’s disease, the brain can absorb ketones more easily than glucose [2, 3].
Proper energy balance is important for brain health. Previous research suggests that prolonged brain energy shortage leads to neuronal death, impaired amyloid-β and tau protein clearance, and the development of Alzheimer’s disease [4]. This suggests that restoring the brain’s energy balance can be a potential therapeutic strategy.
Better cognitive scores
The authors of this study decided to “collect and systematically evaluate the clinical randomized controlled trials” addressing the impact of a ketogenic diet on Alzheimer’s disease. The researchers identified ten trials from the United States, Japan, Canada, China, and New Zealand. Those studies enrolled 691 participants diagnosed with Alzheimer’s disease, but due to 40 participants dropping out, 651 participants were included in the final analysis. These trials lasted between 12 to 60 weeks.
The studies differed in their exact diets. One study used a standard ketogenic diet (macronutrient ratio of 58% fat, 29% protein, 7% fiber, and 6% net carbohydrates by weight). Eight studies used the medium chain triglycerides diet (MCT), a diet that uses lab-made types of fats that produce ketones more easily than fats normally found in food. One study selected the modified Atkins diet (MAD).
The studies included in this analysis used different cognitive function assessment tests, including the Mini-Mental State Examination (MMSE), a commonly used “screening tool for cognitive disorders,” the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog), the Nishimura Mental State Scale (NM scale), and the Activities of Daily Living (ADL) scale. ADAS-Cog is a scale used to assess the memory of Alzheimer’s disease patients. The NM scale measures abilities in daily life. Using different assessment scales and obtaining similar results adds to the credibility of these studies.
In total, these studies concluded that ketogenic diets have an overall positive impact on Alzheimer’s disease patients’ cognitive function. A meta-analysis showed significant changes caused by the interventions in studies that used the MMSE, ADAS-Cog, and NM scales but not ADL.
Changes in blood lipids
Some of the studies also looked at the biochemical profiles of the study participants. Four out of ten studies also analyzed blood lipid profiles. A ketogenic diet resulted in significantly elevated concentrations of triglycerides and low-density lipoprotein-cholesterol (LDL-C), the “bad” cholesterol, but not total cholesterol nor high-density lipoprotein-cholesterol (HDL-C), the “good” cholesterol.
Keto’s dark side
The authors recognize that despite the positive cognitive test results and possible positive implications of ketogenic diets for Alzheimer’s disease patients, this diet and those studies have their shortcomings.
First, the researchers noted that the studies they analyzed have a relatively short duration (typically around three months). While this is convenient from a research perspective and allows for initial evaluation of the diets’ impact, there is a lack of information and monitoring of long-term health effects.
Additionally, long-term adherence to such a strict diet might be difficult; even during the short period of the study, some participants withdrew due to incompatibility.
Some other studies observed some negative health effects of keto diets. It was reported that a strict ketogenic diet could possibly lead to symptoms such as constipation [5], fatigue, headache, nausea, and low blood sugar (hypoglycemia) [6] or more serious reactions such as dehydration, hepatitis, inflammation of the pancreas (pancreatitis), disturbances in sodium, magnesium and uric acid blood levels [7], decreased bone mineral density, kidney stones, heart issues, and anemia [8]. Also, the increase in triglycerides and LDL-C might increase the risk of cardiovascular diseases.
Limitations
This is a review that is built from data gathered by other researchers. The included studies were not all conducted under the same conditions, and the differences between diets and study durations limit how the data can be interpreted. Some studies were also not conducted with large sample sizes.
Overall, this study provides compelling evidence for the potential of KD in the treatment of Alzheimer’s disease, while also highlighting the need to carefully consider potential health risks associated with its use. Future research could explore optimising KD formulations and intervention strategies to maximise cognitive improvements while minimising associated health risks.
Literature
[1] 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.
[2] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 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.
[7] Włodarek D. (2019). Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer’s Disease and Parkinson’s Disease). Nutrients, 11(1), 169.
[8] 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.
