Our brain is arguably the most important organ in the body. It is responsible for both conscious thought and action as well as subconscious processes such as heartbeat, breathing, temperature regulation, digestion. Because the brain plays such an amazing role in the body, it also is the organ that requires the highest amount of energy on a daily basis. The body has several forms of energy that it can use: glucose (or sugar) in the bloodstream, glycogen (or stored sugar in the liver or in the muscle tissue) or fatty acids/ketones (which come from the release and breakdown of body fat). On a daily basis, the brain needs about 120g of glucose (or 480 calories) to operate.
It was once thought that the brain could only run on glucose and therefore, we would need to feed the body enough glucose on a daily basis or else brain function (and therefore body function) would suffer. This myth has been debunked; however, most of the medical establishment still pushes this idea on us as an important reason to eat our whole grains and other metabolically unnecessary carbohydrates each day.
We now know that the brain can burn ketones (which is a form of fat that the body generates from the breakdown of stored fat) for fuel instead of just glucose. In fact, brain cells (neurons) can actually produce their own ketones for fuel when glucose levels are low. This means that the brain is well-equipped to handle periods of low glucose consumption via the use of ketones for fuel. In addition, the liver can meet any small glucose demands by producing glucose from stored glycogen via a process called gluconeogenesis (AKA the production of new glucose).
We actually want our brain to run on ketones more so than glucose. The problem is that we need to teach our brains to do this by becoming fat-adapted. We do this by going through periods of very reduced carbohydrate and high healthy fat consumption which forces our body to produce ketones for energy. When ketones are high, the brain will use them as a fuel source. However, unfortunately, most of us are still eating off of the Food Pyramid from the 1990’s that suggests 6-11 servings of grains per day. Consumption of grains like this means that we are eating a ton of glucose all day, every day. When we feed the brain like this, there is no chance for the brain to use ketones and, actually, this type of eating pattern can be very damaging to our brain cells.
Alzheimer’s Disease (AD) is now being called type 3 diabetes. This is because research is showing a strong connection between the brain’s inability to use glucose and the presence of pathological markers of AD such as tau and amyloid-beta plaques. This is very similar to the insulin resistance we see in type 2 diabetes.
A little primer on type 2 diabetes: When we eat excessive glucose (as recommended by the Food Pyramid--food items such as bread, rice, pasta, crackers, cookies, potatoes, chips, muffins),
the glucose enters our bloodstream and causes our blood glucose to rise. In order to bring our blood glucose back down to normal levels, the body releases insulin--the hormone whose job it is to take excess blood glucose out and store it (either as glycogen or body fat). If we are constantly eating glucose and constantly causing our blood glucose to rise, our body needs to continually release insulin to level out our blood sugar. Over time, insulin stops working as well, or more accurately, our cells stop responding the the insulin and we become insulin resistant. In other words, our body releases insulin but insulin is not able to level out our blood glucose as it once did and we exist in a chronically elevated state of blood glucose and of insulin.
When this chronic elevation of glucose and insulin resistance happens in the brain, it results in the brain cells inability to use glucose for fuel. Growing evidence supports the concept that AD is fundamentally a metabolic disease that results in progressive impairment in the brain's capacity to utilize glucose and respond to insulin. Elevated insulin in the brain also is involved in the phosphorylation of tau and in the formation amyloid plaques, both of which are pathological hallmarks of AD as well as chronic traumatic encephalopathy (CTE) which is consistently being found in the brains of deceased NFL players and is believed to be partly the result of repetitive hits to the head.
So where is the connection between intermittent fasting and NFL players?
Well, intermittent fasting may be key in improving insulin sensitivity in the brain as well as in the body’s own process of healing and preventing the formation of the tau and amyloid plaques and tangles found in AD and CTE.
Intermittent fasting involves periods of fasting followed by periods of feeding. It is not the same as trying to reduce your daily caloric consumption by 500 calories per day in order to burn a pound of fat per week. Not only does that not work, it is also detrimental to the metabolism because the body responds to this type of daily caloric restriction by lowering our metabolic rate and ultimately slowing down our metabolism. This is why most diets fail. Most diets start with caloric restriction day in and day out. Over time, the body adapts to this constant caloric restriction by reducing metabolic rate which means we burn even less calories per day than we did before we started dieting. This sets us up for weight regain and is why almost all diets that involve chronic caloric restriction fail in the long run.
Unlike chronic caloric restriction, research on intermittent fasting shows that this type of eating plan actually increases our metabolism, improves blood sugar regulation and, most importantly for brain health--improves insulin sensitivity and teaches our brain how to be fat-adapted and utilize ketones for energy. In terms of specific benefits to football players beyond brain health, intermittent fasting maintains lean muscle mass and can boost human growth hormone (the body’s anti-aging/repair hormone) by a whopping 2000%!
Examples of intermittent fasting eating patterns include:
Fasting for 16 hours each day (from 8pm the night before until 12pm the next day) and eating for an 8 hour window each day (noon-8pm)
Eating every other day (on fasting days, you are allowed coffee, tea, bone broth, water, soda water, and small amounts of healthy fats/green vegetables--less than 300-500 calories per day)
Doing a 3-7 day fast monthly, every other month or a couple times per year
The beauty of fasting is that it can easily be adapted to what is happening in your life. There are better days to fast than other. Better times of the year to fast than others. The most important part about fasting is that it is intermittent--meaning, it doesn’t have to happen the same way all the time as we see with chronic daily caloric restriction. Because it is intermittent, the body doesn’t have a chance to adapt to it in a negative way by slowing the metabolism. In fact, it “adapts” to intermittent fasting by improving insulin sensitivity, and activating signaling pathways that enhance mitochondrial health, DNA repair and autophagy. All of which are essential to brain health.
Autophagy, in particular, is very important to cellular health including brain cell health. Every cell in the body contains working parts called organelles and proteins and other various components. Think of each cell as a machine with several parts that all have jobs to do to keep us functioning at our best. Over time, just like any hard working machine, these parts start to function less. In a machine such as an automobile, when a part stops working like it should, we repair it or replace it. For example, the transmission stops functioning like it should? We ask the mechanic to replace our transmission. A flat tire? We get a new one. In the body, the process of repairing, recycling and replacing parts of the cell that are no longer functioning is called autophagy.
Autophagy literally means “self-eating.” In other words, our body has cells called macrophages that can eat a non-functioning cell, separate it into its parts and then re-use those parts to build up new cells and new parts. It’s the body’s way of “cleaning up” what’s old and damaged and replacing it with something newer and better. Autophagy is great because it also results in a “clean up” of things that can be damaging and inflammatory such as damaged DNA and, in the brain, the plaques and tangles that damage brain cells in AD and CTE and lead to neurodegeneration.
When autophagy is reduced, as seen in type 2 diabetes, insulin resistance, AD and CTE, the brain is more susceptible to a build up of the plaques and tangles.
If intermittent fasting enhances autophagy, then it has strong potential to lead to a reduction in the build up of plaques and tangles and ultimately a reduction in the symptoms and pathologies of AD and CTE. Remember, intermittent fasting also teaches the brain to burn fat (ketones) for fuel and so it helps prevent the metabolic disturbances and insulin resistance in the brain from happening in the first place.
So putting the big picture together: Intermittent fasting has several health benefits but when looking specifically at brain health, intermittent fasting can be especially beneficial. NFL players and other folks who have a genetic predisposition or are more susceptible to CTE and other neurodegenerative diseases such as AD need to do everything they can to maintain brain health and function. By using intermittent fasting, football players can theoretically reduce the accumulation of the plaques and tangles of AD and CTE through enhanced/improved autophagy. They can also teach their brains to run on ketones which burn cleaner (generate less reactive oxygen species) than glucose. This allows their brains to be highly insulin sensitive, gives neurons an alternative fuel source and reduces the chances of developing the mitochondrial dysfunctions that may lead to the hallmark pathologies of AD and CTE.
Kandimalla R, et al. Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal. Biochim Biophys Acta. 2016 Aug 25. pii: S0925-4439(16)30215-0. doi: 10.1016/j.bbadis.2016.08.018.
de la Monte SM. Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol. 2008 Nov;2(6):1101-13.
Busquets O, et al.Long-term exposition to a high fat diet favors the appearance of β-amyloid depositions in the brain of C57BL/6J mice. A potential model of sporadic Alzheimer's disease. Mech Ageing Dev. 2016 Nov 15. pii: S0047-6374(16)30085-9. doi: 10.1016/j.mad.2016.11.002. [Epub ahead of print]
de la Monte SM.Contributions of brain insulin resistance and deficiency in amyloid-related neurodegeneration in Alzheimer's disease. Drugs. 2012 Jan 1;72(1):49-66.
Chen Z, et al.Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies.
Prog Neurobiol. 2013 Sep;108:21-43.
Moro T, et al. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. J Transl Med. 2016 Oct 13;14(1):290.
Mattson MP, et al. Impact of intermittent fasting on health and disease processes.
Ageing Res Rev. 2016 Oct 31. pii: S1568-1637(16)30251-3.
Halagappa VK, et al. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2007 Apr;26(1):212-20.
Cherry JD, et al.Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy. Acta Neuropathol Commun. 2016 Oct 28;4(1):112.
Woerman AL, et al. Tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):E8187-E8196.
Albayram O, et al. Function and regulation of tau conformations in the development and treatment of traumatic brain injury and neurodegeneration. Cell Biosci. 2016 Dec 5;6:59.
Hu YB, et al. ROCK1 Is Associated with Alzheimer's Disease-Specific Plaques, as well as Enhances Autophagosome Formation But not Autophagic Aβ Clearance. Front Cell Neurosci. 2016 Nov 2;10:253.
Joshi G, et al.Increased Alzheimer's disease-like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy. Neurobiol Aging. 2015 Feb;36(2):664-79.
Feng T, et al. Autophagy-Mediated Regulation of BACE1 Trafficking and Degradation. J Biol Chem. 2016 Dec 27. pii: jbc.M116.766584.
Whyte LS, et al. Endo-lysosomal and autophagic dysfunction: A driving factor in Alzheimer's disease? J Neurochem. 2016 Dec 27. doi: 10.1111/jnc.13935.
Yang DS, et al. Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits. Brain. 2011 Jan;134(Pt 1):258-77.
Yang DS, et al.Therapeutic effects of remediating autophagy failure in a mouse model of Alzheimer disease by enhancing lysosomal proteolysis. Autophagy. 2011 Jul;7(7):788-9.
Ułamek-Kozioł M, et al. Neuronal autophagy: self-eating or self-cannibalism in Alzheimer's disease. Neurochem Res. 2013 Sep;38(9):1769-73.
Jeong JH, et al. Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis. Exp Ther Med. 2016 Nov;12(5):3021-3028.
Amigo I, et al. Dietary restriction in cerebral bioenergetics and redox state. Redox Biol. 2014 Jan 11;2:296-304.
Michalsen A, et al. Fasting therapy for treating and preventing disease - current state of evidence. Forsch Komplementmed. 2013;20(6):444-53.