The Ketogenic Diet for Alzheimer’s – How Ketones Affect The Brain
What is Alzheimer’s?
Alzheimer’s disease, first reported by German psychiatrist Alois Alzheimer in 1907, is a form of progressive dementia[*].
Researchers estimate that over 25 million people have Alzheimer’s dementia worldwide[*]. It is the cause of the majority of dementia cases.
Women experience Alzheimer’s at a higher rate than men, and are more likely to get it earlier in life[*].
Doctors typically divide the disease into early, middle, and late stages.
Early-stage Alzheimer’s is challenging to detect and may resemble the normal effects of aging on memory. The cognitive decline usually starts gradually, getting worse over time.
Most patients don’t receive a diagnosis until difficulties with learning and memory loss disrupt their daily lives[*].
- Episodes of forgetfulness
- Forgetting names of acquaintances
- Confusion in unfamiliar situations
- Difficulty recalling recently-learned information
- Repeating conversations
- Deepening confusion over time
- Disrupted sleep
- Inability to understand one’s location
- Problems speaking
- Emotional and “acting out” symptoms such as depression, anxiety, verbal abuse, or paranoia
Over time, challenges like the inability to recognize people, wandering, and aggression lead to an increasing need for care.
Eventually, the progression of Alzheimer’s results in a total loss of independence for patients. In the advanced stages, they may be totally dependent on caregivers for basic needs like eating and using the bathroom.
From the time of diagnosis, life expectancy is three to nine years[*].
Most of the time, complications of the disease such as dehydration, muscle wasting, or infections result in death.
What Causes Alzheimer’s?
The causes of Alzheimer’s are complicated, and not all researchers agree about them.
In fact, it’s a bit misleading to speak of a “cause” of Alzheimer’s in the first place.
Here’s a more scientific way to consider why and how the disease manifests:
- Risk factors: traits that increase an individual’s risk of Alzheimer’s disease.
- Etiology: a triggering event or process that initiates the disease.
- Pathophysiology or pathogenesis: the disease process itself, or the precise ways in which the disease affects the individual.
Not surprisingly, research in all of these areas is critical for understanding, preventing, and treating Alzheimer’s.
For example, becoming familiar with risk factors can help you understand your risk. This is useful for risk reduction, early detection, and making important decisions ahead of time.
Studying the etiology of Alzheimer’s, which happens to be the least understood aspect relatively speaking, could lead to more effective prevention strategies.
And the better scientists and doctors understand the pathophysiology of Alzheimer’s, the more hope there is for improved treatments that slow or reverse the course of the disease.
Keep reading to learn more about risk factors for Alzheimer’s, as well as leading theories on its origins and progression.
Risk Factors for Alzheimer’s Disease
According to scientific evidence, here are the key risk factors for Alzheimer’s disease:
- Carrying one or two copies of the APOE4 gene[*]
- Familial history[*]
- Traumatic brain injuries (TBIs), also called concussions[*]
- Insulin resistance[*]
- High blood pressure[*]
- Chronic inflammation[*]
- Being overweight or obese[*]
While age is the risk factor with the highest predictive value, it’s not very helpful on a personal level. After all, everyone gets older.
The single most predictive genetic marker for Alzheimer’s disease is having at least one copy of the APOE4 gene mutation, which can raise your risk two- to three-fold[*]. On the other hand, the APOE2 gene mutation may be protective against Alzheimer’s[*].
Having a close relative with Alzheimer’s is known to increase the risk of Alzheimer’s by up to 73%[*].
Other factors, such as concussions, insulin resistance, and high blood pressure, can all have a significant impact on risk. For example, high blood pressure in mid-life can increase your risk of Alzheimer’s by 60-95%[*].
A 2017 study published in the journal Alzheimer’s Research & Therapy concluded that up to a third of Alzheimer’s cases may be preventable if people take action to change modifiable risk factors[*].
And as you’ll learn in the next section, risk factors like inflammation, high blood pressure, and obesity also relate to leading theories of how Alzheimer’s disease begins and progresses.
Leading Theories of Alzheimer’s Disease
Family history and risk genes don’t explain anywhere near 100% of Alzheimer’s cases.
Therefore, something must be happening that causes some people to get the disease when others do not.
At one time, the leading theory of Alzheimer’s disease was the beta-amyloid plaque theory.
Researchers had observed for decades that the brain changes during Alzheimer’s disease. During autopsies, they noticed messy “tangles” caused by a type of plaque called beta-amyloid in the brains of deceased patients[*].
Because these changes obviously related to the progression of the disease, it seemed like a safe bet that targeting plaque formation could treat or even reverse Alzheimer’s.
As a result, drug companies developed drugs to reduce the formation of beta-amyloid plaque. Unfortunately, these medications have all failed to deliver results in clinical trials[*].
The disappointing results indicate that while beta-amyloid formation definitely occurs in Alzheimer’s, it’s most likely a defense mechanism of the body or a side-effect of the disease, not the primary cause.
New and Improved Theories of Alzheimer’s Disease
More recently, scientists have put forth several new theories:
- The vascular hypothesis, based on findings that Alzheimer’s patients have reduced blood flow to their brains[*].
- Glucose hypometabolism, based on the observation from MRI and PET scans that less sugar reaches the brain cells of Alzheimer’s patients, and that cells have difficulty using it for energy[*].
- Mitochondrial dysfunction, suggesting that damaged mitochondria (the “powerhouses of the cells”) aren’t delivering energy to brain cells in Alzheimer’s[*].
- The radical oxidative species (ROS) damage hypothesis, which theorizes that poorly functioning cells impacts the brain adversely by producing damaging free radicals[*].
The odds are pretty high that several of these theories are correct. In fact, they may all be right.
Essentially, reduced blood flow to a person’s brain may result in cellular damage, which prevents the metabolism of glucose.
That could lead to mitochondrial damage and further damage to brain cells, producing vast amounts of free radicals, which spiral out of control and lead to Alzheimer’s disease.
And unlike the beta-amyloid plaque theory, the newer theories do correlate to known risk factors for Alzheimer’s.
- Traumatic brain injuries and concussions impair blood flow to the brain and create free radicals[*]
- Obesity, high blood pressure, and smoking damage the delicate lining of blood vessels[*][*].
- Insulin resistance, inflammation, and obesity result in mitochondrial dysfunction and excessive free radical production[*].
Here’s where things get really interesting.
The ketogenic diet can directly address blood flow, glucose metabolism, and mitochondrial dysfunction, as well as related risk factors like hypertension, inflammation, and obesity.
In the next section, you’ll find out the currently known facts regarding ketosis and brain health.
What Does Ketosis Do to the Brain?
Ketosis refers to the natural production of ketone bodies by your liver. Ketone bodies, or ketones for short, are energy-rich molecules that your body produces in the absence of carbohydrates.
When you’re producing ketones, it means your body is running on fat for fuel instead of relying on carbs and sugar.
To achieve and maintain ketosis, you must eat no more than 30-50 grams of carbs per day.
When it comes to the brain, there are two key aspects to understand about ketosis and the keto diet:
- Ketones have measurable effects on your brain.
- The absence of carbohydrates also has effects on brain tissue and brain function.
In other words, certain brain effects of ketosis are due to the presence of ketones, while others are due to the absence of carbohydrates from your diet.
You can also achieve some of the effects of ketosis by using supplements like medium-chain triglyceride oil (MCT oil) and ketone esters, without eliminating carbs[*][*] .
Here’s what you need to know about ketones and the brain:
- Ketones are the most efficient brain fuel, and absorb more readily than glucose (simple sugar)[*].
- Ketones have anti-inflammatory and antioxidant effects in the brain, meaning they can prevent or limit damage to cells[*].
- Ketones in your brain result in epigenetic changes, including DNA methylation and gene expression[*][*].
And here’s what happens to your brain when you dramatically reduce carb intake:
- There’s less free radical production from glucose, meaning less cellular damage[*].
- Your body, including your brain, become more sensitive to the effects of the hormone insulin[*][*].
- Similar to a fasting state, autophagy and mitophagy take place–meaning your brain can eliminate or “recycle” damaged tissue, cells, and mitochondria[*].
Remember, the above facts are what we know from current peer-reviewed research. These findings are general, and are not specific to people with Alzheimer’s disease.
By now, you might be wondering what the implications are for Alzheimer’s. Keep reading to find out!
Can a Keto Diet Prevent Alzheimer’s?
Let’s establish an essential fact up front: there’s no research yet definitely proving keto can prevent Alzheimer’s.
However, there are plenty of promising findings. In this section, you’ll learn how keto might reduce your risk of Alzheimer’s by improving modifiable risk factors.
Keto and Modifiable Risk Factors
As discussed in a previous section, up to a third of all Alzheimer’s cases may be preventable by targeting the risk factors that can be changed (as opposed to aging, genes, or familial history, which are not modifiable)[*].
First of all, let’s review the known modifiable risk factors:
- Traumatic brain injury (TBI)
- Insulin resistance
- High blood pressure
- Chronic inflammation
- Overweight or obesity
Some researchers have begun calling Alzheimer’s “type 3 diabetes” because severe insulin resistance increases risk of the disease by up to four-fold[*][*].
The pathogenesis of Alzheimer’s dementia has a lot in common with diabetes, too. Diabetes and Alzheimer’s both involve glucose hypometabolism, mitochondrial dysfunction, and free radical damage.
Insulin resistance occurs primarily because of excessive carbohydrate intake. So it’s hardly surprising that a low carbohydrate keto diet is a fantastic way to improve insulin sensitivity, including in your brain.
Numerous studies demonstrate that going keto can help you achieve better scores on blood tests like fasting insulin, fasting blood glucose, and glycated hemoglobin[*][*].
In other words, insulin resistance increases Alzheimer’s risk, but keto can increase insulin sensitivity.
For even better results, pair keto with regular exercise.
High Blood Pressure
So far, so good! How about blood pressure?
According to a systematic review from The British Journal of Nutrition, keto can result in significant drops in blood pressure[*].
Not only that, the effect goes above and beyond what can be explained by sodium restriction and weight loss.
In other words, keto may have a unique ability to lower blood pressure not found with other diets. That’s excellent news when it comes to lowering your risk of Alzheimer’s.
Chronic inflammation in your body can increase your risk of Alzheimer’s disease.
High blood sugar, for example, is a known cause of chronic inflammation, and also correlates to Alzheimer’s risk[*][*].
Keto enhances your mitochondrial health and reduces oxidative stress. It also boosts your body’s natural ability to suppress inflammation[*].
Overweight or Obesity
The fact that keto is fantastic for losing weight is hardly a secret.
But unlike other diets, the ketogenic diet allows you to lose weight with minimal hunger and plenty of energy[*].
Not only that, most people don’t even need to count calories to lose weight on keto[*].
All you need to do is study up on keto macros, make a keto grocery list, and follow through consistently. (It’s also a good idea to measure your ketone levels when you start, to make sure you’re actually in ketosis.)
If you smoke, quitting may lower your risk of Alzheimer’s disease by up to 58%[*].
But how does that relate to the ketogenic diet?
Believe it or not, a 2010 study published in the journal Trials concluded going keto may even make it easier to quit smoking for overweight adults[*]. Win-win!
Can Keto Reverse Alzheimer’s?
The short answer: no one knows yet if keto can reverse Alzheimer’s.
There are no randomized controlled trials of the diet in Alzheimer’s patients, meaning there simply isn’t enough data to say one way or the other.
However, some doctors do currently use the ketogenic diet to treat Alzheimer’s[*].
There’s also promising evidence demonstrating improved cognition from studies of mild cognitive impairment (MCI) patients given ketogenic supplements like MCT oil and exogenous ketone bodies[*][*].
And according to the authors of a 2019 study from the high-impact journal Nutrition[*]:
“the ketogenic diet could be an effective treatment and prevention for Alzheimer’s disease, but both ketone production and carbohydrate restriction may be needed to achieve this.”
Next, we’ll take an in-depth look at how ketosis interacts with known mechanisms that contribute to the progression of Alzheimer’s.
Ketosis and Alzheimer’s Pathogenesis
As covered previously, here are the four key pathways that appear to contribute to Alzheimer’s progression:
- Vascular dysfunction and blood-brain-barrier issues
- Glucose hypometabolism (insufficient glucose)
- Mitochondrial dysfunction, resulting in reduced energy production in the brain
- Free radical damage, which creates a vicious cycle in combination with the other three mechanisms
Can keto help address these disease progression mechanisms?
Here’s what current evidence suggests.
According to recent research, going keto may increase cerebral blood flow and help repair the vascular damage that occurs in Alzheimer’s patients[*][*].
Evidence also demonstrates that the keto diet compensates for glucose hypometabolism by supplying ketones as an alternative fuel source[*].
And a study of 23 adults with mild cognitive impairment, which can be a precursor to Alzheimer’s disease, found that ketones improved memory and cognitive function in the participants[*].
Finally, ketones and ketosis work to improve mitochondrial function, delivering more energy to the brain[*]. As a result, they also decrease inflammation and damage from free radicals.
In summation, the keto diet does appear to address the four known pathways that contribute to the progression of Alzheimer’s.
However, the degree to which it can halt or even reverse the disease remains to be discovered.
Does Keto Do More Harm Than Good?
If you’ve done your homework, you already know that the keto diet is controversial.
For every new promising finding, an equal number of doctors, Hollywood celebrities, and internet “experts” warn that you shouldn’t hop on the keto bandwagon.
Let’s take a look at the most common claims about the “harmful effects” of the ketogenic diet and see how they stack up against real evidence.
The Claim: Ketosis is Dangerous
Some doctors believe that ketosis is dangerous because high ketone levels can sometimes occur in diabetes, a condition called ketoacidosis.
Here’s a telling quote from a popular article warning that ketosis is dangerous:
“Ketones affect the pH (acid/base balance) of the blood. We normally have a higher (less acid) pH, but ketones are acidic, and if present at elevated levels, they can lower blood pH, which can seriously mess with our metabolism. The condition called ketoacidosis, which occurs in out-of-control diabetes, can also occur in a poorly composed and monitored ketogenic diet, and this can be serious—even fatal.”
To begin with, ketosis and ketoacidosis are not the same thing.
Doctors who don’t specialize in diet and nutrition sometimes confuse the two. However, in nutritional ketosis, your blood ketone levels are between 0.6-3.0 millimoles per liter (mmol/L), while ketoacidosis occurs when your ketone levels become dangerously high (usually over 10mmol/L).
Ketoacidosis primarily occurs in people with poorly-managed diabetes, not as a result of the keto diet. It can also happen because of alcoholism, drug abuse, hyperthyroidism, heart attacks, or starvation.
It’s dangerous because ketones are acidic, so having insanely high ketone levels leads to all kinds of problems.
While some reports of ketoacidosis associated with a low-carb diet do exist, they are incredibly rare. None have been reported in trials of low-carb or ketogenic diets.
All of the reported cases involve other factors, such as alcoholism or lactation[*]. (Side note: if you’re breastfeeding, talk to your doctor before starting keto, and learn more about keto and breastfeeding here.)
The authors of a 2018 peer-reviewed article on keto and Alzheimer’s summed it up perfectly[*]:
“The pathological ketoacidosis due to a lack of insulin in type 1 diabetes is not possible as [a] result of dietary changes alone.”
Translation: ketoacidosis is not the same as ketosis, and it’s simply not a concern if you approach the keto diet sensibly.
The Claim: Keto and High-Fat Diets are Bad for Your Heart
Until recently, most doctors and scientists believed that high-fat, high-cholesterol diets resulted in “clogged arteries.”
While this theory is now heavily contested, it’s fair to say that keto spooks people who still buy into it.
Robust evidence shows going keto actually improves many cardiovascular risk factors, including lowering “bad” cholesterol levels and raising “good” cholesterol levels[*][*].
When it comes to keto, there’s no substantial reason to be concerned about heart health.
Additionally, some evidence also shows higher total cholesterol may help prevent Alzheimer’s[*]!
The Claim: Keto Causes Nutrient and Fiber Deficiencies
Senior citizens and Alzheimer’s patients are already at an increased risk for malnutrition. That’s why some people worry that putting them on a restrictive diet could lead to nutrient deficiencies.
Along with that, keto eliminates grains and other high-carb sources of fiber, leading to concerns that there’s no good way to get fiber on the diet.
A 2019 paper published in Current Developments in Nutrition found that Alzheimer’s patients can follow a nutritionally-dense keto diet with medium chain triglycerides (MCT oil), avocados, and non-starchy vegetables[*].
In terms of fiber and keto, there’s no excuse to skimp on fiber–you just have to get it from non-grain, whole food sources instead of unhealthy processed foods.
Several large-scale scientific reviews indicate that eating sufficient fiber can reduce your risk of dying from both heart disease and cancer by at least 10%[*][*][*]. The benefits of eating fiber in these studies occurred with a total daily fiber intake between 18-26 grams, which is lower than USDA recommendations (and easily achieved on the ketogenic diet).
And if you follow the ketogenic diet, moderate fiber intake probably is sufficient. Many of the benefits of high fiber diets come from the production of short-chain fatty acids (SCFAs) in your gut, which alter gene expression and reduce inflammation in your body[*][*][*].
If you eat a high-fat keto diet, your diet already includes plenty of butyrate and other SCFAs, and your body also makes anti-inflammatory ketones like beta-hydroxybutyrate[*][*].
As you investigate keto for yourself or a loved one, remember: it’s essential to ensure you include plenty of nutrient-dense foods and keto-friendly whole food sources of fiber.
As long as you do, there’s absolutely no need to fret over fiber.
The Takeaway: Keto For Alzheimer’s
Early research into the keto diet for Alzheimer’s is encouraging.
Keto can certainly help address risk factors for Alzheimer’s.
Preliminary evidence also suggests it interacts favorably with the mechanisms that underlie the progression of Alzheimer’s.
However, if you or someone you know is at risk for Alzheimer’s or has received a diagnosis, you don’t need to wait for more clinical studies.
As long as you stock up on nutrient-dense foods and understand keto macronutrients, the best way to learn more is to try it for yourself.
Keto is safe, works phenomenally well for many different health issues, and is a great way to have more energy, clearer thinking, and fewer cravings.
But if you’d prefer not to dive into keto right away, studies show that using keto supplements like MCT oil or ketones may be helpful, too[*].