It seems so simple and benign – eat sugar and gain a boost in energy. After all, glucose (what we think of as blood sugar) is used by mitochondria to make ATP (the fuel of cellular energy). However, evolution’s failure to adapt to our modern diets means that we can only safely process a small amount of sugar per day. Surprisingly, U.S. government agencies recommend limiting your daily sugar intake to the robust levels of 37.5 grams for men and 25 grams for women. The World Health Organization uses a different formula and recommends that adults should get no more than 10% of their calories – and ideally less than 5% – from added or natural sugar sources. For a 2,000-calorie diet, that’s about 25 grams.
Just for fun, we’ll say that 40 grams of added sugar is unhealthy. Here’s where we always have to stop and say “to put that in perspective…” one medium chocolate milkshake from McDonald’s will give you 47 grams of sugar. In the average American diet men and women consume about 119 grams of sugar daily and over 200 grams of carbs (much of which will be quickly converted by the body into glucose).
When blood sugar levels rise (and this is normal after eating), the pancreas secretes insulin which encourages cells to take the glucose in and feed their mitochondria. The more glucose in the blood the more insulin is pumped out by the pancreas to bring your glucose levels down. When insulin levels climb and levels stay elevated for a long time, the “encouragement” from insulin to the cells starts to sound like horrible nagging and the cells stop listening.
This article isn’t about weight loss it’s about your brain. You see, one explanation for the link between diabetes and Alzheimer’s lies with IDE or Insulin Degrading Enzyme. This is one time that I probably don’t need to explain what the name means. IDE doesn’t just break down insulin, it also degrades other substrates and here’s the really important part, its second favorite substrate to attack is….drum roll….amyloid beta (Aβ). This bears repeating. Excess sugar leads to excess insulin which uses up all the available IDE so that there is none left to degrade amyloid beta.
Is it possible that reducing your sugar intake could lead to a reduction in your amyloid beta load? Studies clearly back up this notion. Mice engineered to produce extra IDE had significant reductions of total amyloid burden and improved survival rates. Mice engineered to not produce IDE had a clear elevation of brain Aβ. And just to further prove the point, mice that produced reduced levels of IDE had elevated Aβ levels compared to wild-type controls. In fact, that last study found that it didn’t take much of a depletion in IDE to result in an increase in Aβ. It stands to reason that tipping the balance away from insulin degradation (by reducing insulin production) would lead to a reduction in Aβ deposits.
Insulin also shuts down autophagy. Autophagy recycles amino acids from various sources in the cell, but the important one here is mis-folded proteins. In other words, without the inhibition of insulin the cell is more likely to experience autophagy and will destroy both amyloid-beta and tau proteins and their associated plagues and tangles.
The role of IDE and autophagy demonstrates that excess glucose is a contributing factor to the development of Alzheimer’s, but what about regular glucose levels?
Neurons require lots of energy and normally most, if not all, of that energy comes from glucose metabolism a process where the mitochondria of the neuron convert glucose into ATP. The brain is only about 3 lbs (1.4 Kg) and yet it devours about 20% of glucose-derived energy in the body. Ordinarily, tight regulation of glucose metabolism is critical for proper brain function. Therefore, hypometabolism in the brain is a leading suspect for several neurodegenerative diseases.
In Alzheimer’s and the lead up to Alzheimer’s glucose metabolism is impaired (hypometabolism). Alzheimer’s begins up to 20 years before symptoms appear and studies (such as this one) show that hypometabolism is right there at the start. Specifically, the dysfunction results in mitochondria producing less ATP and more free radicals which contributes to issues of oxidative stress, inflammation, cytokine cascades, and cell death. For carriers of the ApoE4 allele (E4), impaired glucose metabolism may be the earliest indication of future disease.
Prevention and Treatment
Finally the good news. When glucose levels drop low enough, as happens during fasting or low carbohydrate intake, the liver will produce ketone bodies (also called ketones) from energy-rich fat stores. This is called ketosis and the brain functions quite well in this state.
Ketosis can be maintained with a ketogenic diet (low carb and high fat). You may recognize this as the Atkin’s diet that has enjoyed popularity and controversy since its introduction in the early 70’s. Many associate a ketogenic diet with weight loss and while that can certainly be a benefit, it really is possible to maintain your weight and improve your brain function by replacing carbohydrates and sugar with fat.
Say what?! Yes, despite the sugar industry’s successful campaign to shift the blame for poor health from sugar to fat, studies over the past 20 years (without ties to the sugar industry) have shown that just drinking too much soda can lead to obesity and metabolic disease (i.e. diabetes and probably Alzheimer’s).
If the Alzheimer’s and pre-Alzheimer’s brain has trouble using glucose and the brain functions well on ketones….
Ketosis and Alzheimer’s
The principal ketones, β-hydroxybutyrate and acetoacetate, are the brain’s main physiological alternative fuel to glucose. Unlike with glucose, brain ketone uptake does not diminish with age. Perhaps because the mitochondria convert ketones into ATP in 3 steps versus the 11 step processes using glucose, which produces fewer reactive oxygen species (the free radicals that cause oxidative stress).
Several studies have shown that ketosis has a positive effect on cognitive ability in patients suffering from Alzheimer’s. A 2012 study randomly assigned participants with MCI into either a high carb or high fat diet. After 6 weeks the low carb group showed improved verbal memory performance. The one correlation that stood out in the study was between insulin and memory in the low carb group. Specifically, the lower the insulin levels the better the memory function. The researchers concluded that “very low carbohydrate consumption, even in the short term, can improve memory function in older adults with increased risk for Alzheimer’s disease.”
Alzheimer’s patients showed improved cognitive scores relative to placebo when given medium chain triglycerides (MCT) to induce ketosis. Medium Chain Fatty Acids (MCTs) are saturated fats (most commonly coconut oil) that are converted by the liver directly into ketones and are often used to speed up the transition into ketosis. In the past it was assumed that because MCTs are saturated fats they would increase cardiovascular risk factors and body weight, but recent evidence casts doubt on those assumptions. This 2013 study showed that treatment for 30 days with 30 g/day of MCTs did not adversely affect body weight, body fat content, or BMI, nor did it affect serum glucose, insulin, triglycerides, cholesterol, or free fatty acids.
Ketosis can correct two big Alzheimer’s related issues. By switching your body’s energy source from glucose to fat you will greatly reduce your levels of insulin and allow IDE to switch to degrading amyloid beta. Furthermore, allowing the body to produce ATP from ketones will avoid the less efficient and free-radical producing process of converting glucose to energy.
I won’t “sugar-coat” this, ketosis takes effort to achieve and some serious will power to maintain in the beginning. In all likelihood it will turn your regular diet upside down and require you to change what you eat, but especially it will produce a long list of tasty items you can no longer eat (at least not in the quantities you did in the past). Like anything new, it can become routine and therefore much easier to sustain. Regardless of how difficult it may be initially, the alternative may be all the motivation you need.