Alzheimer’s Disease: A Third Type of Diabetes

Alzheimer’s is a devastating neurodegenerative disease with an incidence rate that is on the rise in America. Despite being discovered in 1906, strikingly little progress has been made in the fight against it. Today we can offer a patient afflicted with this disease no more help than we could have offered them one hundred years ago. It is well known that consuming excessive amounts of sugar can lead to the impairment of brain function and can cause the buildup of plaque within the brain in the long term. And it has been concluded that a diet high in carbohydrates worsens cognitive ability in Alzheimer’s patients (Gasior, Rogawski, & Hartman, 2010). Alzheimer’s is certainly not a normal part of the aging mind and recent studies show that it may be possible to slow its progression and reverse some neurodegeneration. And just like it has been shown that a ketogenic diet can significantly improve the prognosis of type 2 diabetes, studies involving the supplementation of the ketone body, β-Hydroxybutyrate, in Alzheimer’s patients resulted in improved cognitive performance. It can be concluded that the term ‘type 3 diabetes” (T3D), referring to Alzheimer’s, accurately reflects a form of diabetes—pathologically similar to type 2 diabetes (T2D)—selectively involving the brain, with a progression that may be stopped and even reversed in its early stages through a ketogenic diet (Steen et al., 2005).

The hippocampus is the region of the brain most involved in the formation of memories and it has been shown to regulate memories using insulin. It is lined with insulin receptors that become damaged as insulin resistance develops (McNay et al., 2010). And on average, those afflicted with Alzheimer’s have almost 80% fewer insulin receptors within the brain when compared to a healthy person (Song, Whitcomb, & Kim, 2017); and studies have shown that a relative lack of insulin receptors within the brain directly leads to an increase in the occurrence of memory dysfunction (Song et al., 2017). Insulin resistance within the brain also stunts neurogenesis and leads to an increase in misfolding in proteins associated with memory formation and recall (Steen et al., 2005). This misfolding has been linked with the harmful plaque buildup that is often seen within the brain of an Alzheimer’s patient. It is often the result of a degraded blood-brain barrier (BBB); a highly selective border of cells that decides what can enter the brain’s bloodstream, thereby protecting it from potential harm. An excess of glucose flowing through the brain is associated with the degradation of the cells comprising the BBB. When the BBB is harmed, small crevices form allowing proteins among other molecules into the brain. A small portion of these proteins are misfolded and form plaques lining the brain’s vasculature (Song et al., 2017). It is not completely understood why these plaques form, but scientists are almost certain that insulin resistance plays a big role (Mullins, Diehl, Chia, & Kapogiannis, 2017). One of the side effects of insulin resistance is the formation of harmful free radicals; these radicals can increase inflammation within the brain which has also been associated with the build-up of plaques thereby diminishing cognitive performance (Tangvarasittichai, 2017).

The link between insulin resistance and dementia offers some clues into potential treatment because T2D is an avoidable lifestyle disease. Through changes in one’s diet it possible to reduce the chances of developing T2D thereby also reducing one’s chances of developing T3D. The ketogenic diet was originally used to treat drug-resistant epilepsy for which it is a proven therapy (Rogovik & Goldman, 2010). Because a ketogenic diet involves eating foods high in fat and low in carbohydrates, it results in greatly reduced levels of insulin in the blood and therefore glucose (Kinzig, Honors, & Hargrave, 2010). When the human body lacks carbohydrates to use as fuel it begins to produce something called ketone bodies, from fat. Why is this important? The brains of people afflicted with neurodegenerative diseases have a hard time burning glucose; over time this leads to a sluggish brain and neuronal atrophy (Mosconi, 2013). The brain of an Alzheimer’s patient is essentially experiencing an energy crisis, therefore needing an alternative source of fuel; and barring extremely advanced cases of Alzheimer’s, the human brain can run efficiently on ketone bodies (Taylor, Sullivan, Mahnken, Burns, & Swerdlow, 2018).

The ketogenic diet has also been found to be therapeutic in the treatment of people with mild cognitive impairment (MCI); a pre-Alzheimer’s stage (Krikorian et al., 2012). 23 elderly people were given either a high-carb or low-carb diet for six weeks. At the end of the study, the elderly on the low-carb diet showed improved verbal fluency and memory performance along with a reduction in abdominal fat. This indicates that the consumption of very few carbohydrates, even in the short-term, results in increased cognitive performance in adults who have an increased risk of developing Alzheimer’s disease (Krikorian et al., 2012).

Even when MCI has progressed to Alzheimer’s, there is evidence that a ketogenic diet can still provide relief of symptoms and slow the progression of the disease. In one study, a 50-year-old man afflicted with Alzheimer’s showed a significant improvement in memory when medium-chain triglycerides were added to his diet (Cunnane et al., 2016). In a different study where people with varying degrees of dementia also had medium-chain triglycerides added to their diet, cognitive improvement also occurred. Of the 60 participants in the study, 90% showed improvement many areas including sleep, memory, increased appetite, visual acuity and verbal fluency (Murray et al., 2016). In one randomized study 150 patients with varying degrees of Alzheimer’s, a ketone body obtained from MCT oil was administered as a therapeutic agent in conjunction with a normal diet (Newport, Vanitallie, Kashiwaya, King, & Veech, 2015).

The group with risk factors for Alzheimer’s disease experienced cognitive improvement which correlated directly with blood concentration of the ketone body.

The degree of cognitive improvement was significant in the study group who had genetic risk factors for Alzheimer’s, and correlated positively with blood levels of the ketone agent.

The development of insulin resistance has been shown to be a factor in the progression of Alzheimer’s. (Westwood et al., 2014). While in T2D insulin resistance is typically observed in muscle tissue, the sustained high blood glucose levels associated with T2D can also lead to insulin resistance within the brain. This insulin resistance harms the brain cognitive performance, neurogenesis and promoting inflammation leading to the hallmark effects of Alzheimer’s: impaired memory, reduced ability to communicate, and changes in behavior such as delusion and anxiety. The shared pathogenic pathways between T2D and Alzheimer’s and the fact that treating the root cause of T2D, insulin resistance, with a ketogenic diet, is also therapeutic to Alzheimer’s disease shows that a link between Alzheimer’s and T2D may exist; and that one can even hypothesize that Alzheimer’s might be a type of diabetes, type 3.

 

References

Cunnane, S. C., Courchesne-Loyer, A., Vandenberghe, C., St-Pierre, V., Fortier, M., Hennebelle, M., . . . Castellano, C. (2016). Can ketones help rescue brain fuel supply in later life? Implications for cognitive health during aging and the treatment of Alzheimer’s Disease. Frontiers in Molecular Neuroscience.

de la Monte, S. M., & Wands, J. R. (2008). Alzheimer’s disease is type 3 diabetes-evidence reviewed. Journal of diabetes science and technology, 2(6), 1101-13.

Gasior, M., Rogawski, M. A., & Hartman, A. L. (2006). Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioural Pharmacology, (5-6).

Kinzig, K. P., Honors, M. A., & Hargrave, S. L. (2010). Insulin Sensitivity and Glucose Tolerance Are Altered by Maintenance on a Ketogenic Diet. Endocrinology, (7).

Krikorian, R., Shidler, M. D., Dangelo, K., Couch, S. C., Benoit, S. C., & Clegg, D. J. (2012). Dietary ketosis enhances memory in mild cognitive impairment. Neurobiology of Aging, (2).

McNay, E. C., Ong, C. T., Mccrimmon, R. J., Cresswell, J., Bogan, J. S., & Sherwin, R. S. (2010). Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiology of Learning and Memory, (4).

Mosconi, L. (2013). Glucose metabolism in normal aging and Alzheimer’s disease: Methodological and physiological considerations for PET studies. Clinical and Translational Imaging, (4).

Mullins, R. J., Diehl, T. C., Chia, C. W., & Kapogiannis, D. (2017). Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in Alzheimer’s Disease. Frontiers in Aging Neuroscience.

Murray, A. J., Knight, N. S., Cole, M. A., Cochlin, L. E., Carter, E., Tchabanenko, K., . . . Clarke, K. (2016). Novel ketone diet enhances physical and cognitive performance. The FASEB Journal, (12).

Newport, M. T., Vanitallie, T. B., Kashiwaya, Y., King, M. T., & Veech, R. L. (2015). A new way to produce hyperketonemia: Use of ketone ester in a case of Alzheimer’s disease. Alzheimer’s & Dementia, (1).

Rogovik AL, Goldman RD. Ketogenic diet for treatment of epilepsy. Can Fam Physician. 2010;56(6):540-2.

Song, J., Whitcomb, D. J., & Kim, B. C. (2017). The role of melatonin in the onset and progression of type 3 diabetes. Molecular Brain, (1).

Steen, E., Terry, B. M., Rivera, E. J., Cannon, J. L., Neely, T. R., Tavares, R., . . . Monte, S. M. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease – is this type 3 diabetes? Journal of Alzheimer’s Disease, 7(1), 63-80. doi:10.3233/jad-2005-7107

Tangvarasittichai, S. (2015). Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World Journal of Diabetes, (3).

Taylor, M. K., Sullivan, D. K., Mahnken, J. D., Burns, J. M., & Swerdlow, R. H. (2018). Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions.

Westwood, A. J., Beiser, A., Decarli, C., Harris, T. B., Chen, T. C., He, X., . . . Seshadri, S. (2014). Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy. Neurology, (18).