The ketogenic diet is best known as a weight loss diet. The research shows that going keto can reduce cravings, increase fat burning, and help keep blood sugar low[*]. These are all positive metabolic changes.
As it turns out, going keto also has brain benefits. That’s right. Researchers have uncovered a slew of potential mechanisms by which the ketogenic diet can reduce brain inflammation, tamp down chronic inflammation, and support healthy cognition.
If you’re curious to learn more, keep reading.
Brain inflammation refers to an immune response in the brain driven by aging, injury, infection, or some other condition. In turn, this immune response can negatively impact cognitive function, mood, behavior, and disease risk[*].
Short term brain inflammation often manifests as depression, anxiety, anorexia, sleep issues, and decreased physical activity. Longer term consequences include neurodegenerative disorders like Alzheimer’s and Parkinson’s, as well as certain psychiatric disorders[*].
There are two main causes of brain inflammation:
- Acute infection or injury, such as traumatic brain injury (TBI)
- Chronic, systemic inflammation
#1: Acute Brain Inflammation
Your brain is a delicate organ, suspended in liquid, floating in your skull. If you hit your head too hard, your brain slams into the side of your cranium. This is called a concussion, or traumatic brain injury.
In response to this injury, immune particles called microglia and macrophages rush to the site — and along with them: inflammatory cytokines, or cytokines for short[*].
Cytokines are rallying beacons for the rest of the immune response. They activate a pathway called NFkB, which brings more cytokines — and other immune particles — to the site of injury. The larger the perceived injury, the larger the inflammatory response.
In the case of, say, an infection — this immune response can be desirable. You want your immune system fired up to destroy unwanted pathogens.
But often, the immune response stays too strong for too long. And when inflammation sticks around for too long (as with TBI), brain cells die and the risk of neurodegenerative disease skyrockets[*].
#2: Chronic Inflammation
Brain inflammation is closely linked to chronic, systemic inflammation — a low-level immune activation that underlies most chronic diseases from Alzheimer’s to heart disease to cancer[*].
Chronic inflammation is distinct from acute inflammation. Acute inflammation is your body’s response to injury or infection. It’s an essential part of your immune system.
In the case of TBI, brain inflammation is the “protect and heal” response to head trauma. Unfortunately, however, this inflammation often harms — rather than protects — delicate brain cells.
But in the case of chronic inflammation, there’s no obvious injury or infection present. The immune system gets fired up (and stays fired up) even when you don’t need it.
Again, cytokines are the key inflammatory particles here. Cytokines circulate in a state of chronic inflammation, cross the blood-brain barrier, infiltrate neural tissue, and can cause mind-altering damage[*].
Many researchers, in fact, endorse the “inflammatory cytokine model of depression”. This model places inflammation, not serotonin, as the key driver of a depressed mood[*].
Scientific support? When you inject healthy people with LPS (an endotoxin), the resulting cytokine response drives anxious, sad, and depressed behavior[*]. And so, it appears that an overactive immune system can make you sad.
Okay. So if chronic inflammation causes brain inflammation, what causes chronic inflammation? Here are some major ones:
- Smoking cigarettes
- Genetic predispositions
- High sugar diets
- High intake of vegetable oils (PUFAs)
- Not getting enough sleep
- Not exercising
To be clear, there’s no easy fix for chronic inflammation. The best strategy is to live an anti-inflammatory lifestyle. And of all the aspects of this lifestyle, diet may be the easiest to control.
Inflammation is a complex phenomenon, driven by countless proteins, genes, enzymatic pathways, and other biological factors. Some are within your control, others aren’t.
For the most part, diet is within your control. It’s true: How you eat affects inflammation in the brain and elsewhere.
Along these lines, the keto diet / ketosis has been shown to:
- Protect brain cells of rats after TBI[*]
- Reduce inflammation and seizures in mice[*]
- Improve a mouse-model of multiple sclerosis, an autoimmune disorder[*]
- Enhance cognitive performance in non-demented elderly people[*]
Why these positive results? The next several sections offer a variety of mechanisms to explain.
#1: NADH:NAD+ Ratio
Researchers from UC San Francisco recently found a unique pathway relating to the antiinflammatory effects of keto. It was a clever experiment. They induced ketosis in rats by blocking glucose metabolism, and — after a period of time — noticed the rats had significantly reduced brain inflammation[*].
Here’s why. When you reduce glucose availability (as with a keto diet), you reduce an important energy ratio called NADH:NAD+. The decrease of this ratio activates a protein, called CtBP, which in turn tells your genes: turn off inflammation!
The anti-inflammatory effect of this manipulation wasn’t small.
“I was most surprised by the magnitude of this effect,” the lead author Dr. Raymond Swanson is quoted as saying, “because I thought ketogenic diets might help just a little bit”[*].
Verdict? Decreasing glucose availability with a ketogenic diet has downstream anti-inflammatory effects.
#2: Lower Blood Glucose
Keeping blood sugar, or blood glucose, low is like an insurance policy for your brain. That’s because high blood sugar (hyperglycemia) exacerbates brain damage in the context of brain injury or brain inflammation[*]. High levels of glucose in the brain may even impair cognition[*].
One cause of high blood sugar? High-carb diets. Carbs are sugar, and when you eat them, your blood sugar rises in response to that meal[*]. Then insulin — your blood sugar boss — comes along and cleans up the glucose mess, shoving that sugar into muscle and liver cells for storage.
But chronic high-carb, high-sugar diets — especially combined with poor sleep and a sedentary lifestyle — can lead, over time, to insulin resistance. Insulin resistance? That’s when your cells stop listening to insulin, causing blood sugar to stay high. This, unfortunately, is a recipe for systemic inflammation.
The keto diet may help. Why?
- The keto diet is very low-carb, and minimizes blood sugar spikes
- Ketone bodies like BHB suppress blood sugar levels[*]
- Keto lowers ghrelin — your hunger hormone — so you don’t crave as many carbs[*]
Bottom line? Keto helps prevent high blood sugar, which may reduce brain inflammation.
#3: More Adenosine
Adenosine is a brain chemical — released during injury or illness — that reduces pain and inflammation. In other words, adenosine makes you feel better.
What else stimulates adenosine? Yes, the ketogenic diet.
This has been shown in mice. Researchers fed mice a keto diet and noticed two main things: less seizures, more adenosine[*].
Takeaway? More research is needed, but keto may boost anti-inflammatory adenosine in the brain.
#4: Fewer ROS
Reactive oxygen species, or ROS, are molecules produced as a byproduct of normal energy metabolism. At reasonable levels, ROS serve an essential immune-signaling function[*]. But in excess, these free radicals can damage and inflame every organ system, including the brain[*].
Burning sugar produces plenty of ROS. Burning ketones, on the other hand, produces fewer ROS — and also stimulates cleanup enzymes (like glutathione peroxidase) that sequester free radicals[*].
Most of the evidence is animal evidence. In one study, a ketogenic diet improved a mouse model of multiple sclerosis, probably via reduced ROS[*]. In another, researchers showed that (in mice) a ketogenic diet lowers ROS and increases energy output[*].
Simply put, your cells appear to run cleaner AND more efficiently on ketones than on glucose. More energy, less waste.
And less ROS, all things equal, means less inflammation.
#5: More GABA, less glutamate
Gamma aminobutyric acid (GABA) is an inhibitory neurotransmitter best known for its relaxing effects. Relevant here: higher GABA levels may be neuroprotective[*].
How might keto help? In one study, ketone-fed rats showed higher GABA levels in certain parts of the brain. In humans too, keto was linked to increased GABA levels[*].
Directly opposed to GABA is an excitatory (stimulating) neurotransmitter called glutamate — higher levels of which cause brain inflammation. The ketone body acetoacetate may help reduce glutamate-toxicity, but this has only been shown in a test tube, so more research is needed[*].
Bottom line? By boosting GABA and reducing glutamate-toxicity, keto may promote an anti-inflammatory neurotransmitter environment in the brain.
When you enter ketosis, your cells burn fat to produce the ketone bodies beta-hydroxybutyrate (BHB), acetoacetate, and acetone. Of the three, BHB — which can also be ingested via ketone salts or esters — has been the most vigorously studied for its anti-inflammatory signaling properties.
Why? Because BHB inhibits an immune complex called the NLRP3 inflammasome. To keep things simple, just call it “the inflammasome”[*].
If inflammation is the fire, the inflammasome is the spark. When the inflammasome sparks its spark, the rest of your immune system rushes to the site — and pretty soon you have a bonfire of inflammation. This is great for wound healing, but not so great for long-term damage control.
That’s where BHB comes in. BHB helps regulate the inflammasome by reducing macrophages, cytokines, and other immune particles[*]. It does so, most likely, by reducing the flow of potassium from immune cells. This mechanism not only modulates the immune system, but may also reduce seizures in those susceptible[*].
The takeaway? BHB is a promising signaling molecule for reducing inflammation.
So far you’ve learned how a keto diet may reduce brain inflammation. This anti-inflammatory function, along with a few other mechanisms, drive several brain benefits of going keto.
#1: Better cognition
Recall that hyperglycemia increases brain damage following head trauma. But even without trauma, excess glucose can impair cognition.
In a recent study, researchers gave participants either a glucose or placebo drink, then administered a series of mental performance tests. The glucose group, they found, fared significantly worse than the placebo group on these tests[*].
Why? The authors believe that “the effects are mediated by glucose”. Sugar molecules, as it turns out, cross the blood-brain barrier like hurried passengers streaming into a crowded terminal. Too many glucose passengers, less cognitive performance.
Ketones also cross the blood-brain barrier, but unlike glucose, they appear to enhance cognition. For example, when scientists fed rats a ketone-rich diet, the rats were better able to navigate a complex maze[*]. And in humans, the presence of ketones (from MCT oil supplementation) had “positive effects on working memory, visual attention, and task switching”[*].
Alzheimer’s disease is a neurodegenerative disorder that ranks as the sixth leading cause of death in the United States. Memory loss is usually the first noticeable symptom, with further cognitive impairment to follow[*].
The precise causes of Alzheimer’s are still unknown, but it’s fairly clear that inflammation plays a crucial role. It seems likely that declining mitochondrial function (impaired energy production in the brain) also contributes to the disease[*].
The research is early, but the keto diet may help. Here’s why:
- Brains can use glucose or ketones for energy — but unlike glucose, aging brains can utilize ketones just as well as younger brains. For this reason, some researchers believe the ketogenic diet may offset age Alzheimer’s-driven cognitive decline[*].
- Ketones increase mitochondrial function in the brain, which may be therapeutic for Alzheimer’s[*].
- The keto diet and ketone bodies decrease systemic inflammation through a variety of mechanisms (see the five reasons above) — and systemic inflammation is linked to increased Alzheimer’s risk[*].
The ketogenic diet wasn’t originally a weight loss diet. No, keto was first employed to treat a specific neurological disorder called epilepsy.
The backstory is interesting. Researchers in the 1920s had discovered that fasting had an anti seizure effect, and said, hey, why not try a fasting-mimicking diet to treat epileptic children?[*]
These researchers used a keto diet because keto, in a sense, mimics starvation. In both a fasted and ketogenic state, your body relies on fat as its primary energy source. Both get you into ketosis, but the keto diet gets you there more gently.
The keto diet, as you probably guessed, was highly effective at reducing seizures in children. Deeper ketosis, with more ketones produced, meant less seizures. Later, the same was found to be true for adults[*].
One potential anti-seizure mechanism involves potassium. Specifically, ketosis reduces potassium efflux (outward flow) from cells[*].
Glutamate and GABA may also play a role. Glutamate is excitatory (not desirable for seizures), while GABA is inhibitory. Keto appears to shift these neurotransmitters in the right direction, from an epilepsy-treatment perspective[*].
Epilepsy aside, having more GABA in your system promotes relaxation — and there’s nothing wrong with that.
Bottom line? The keto diet has been shown to reduce epileptic seizures.
The Takeaway: Keto May Reduce Brain Inflammation
Like any other organ, the brain is susceptible to inflammation. Whether this damaging immune response results from acute trauma, infection, or chronic inflammation — the net effect can be devastating for both short and long-term cognitive health.
Minimizing brain inflammation isn’t simply a matter of avoiding head trauma. It’s tricky, because inflammation from anywhere in your body can cross the blood-brain barrier, infiltrate your brain, and affect the neural environment. An anti-inflammatory lifestyle is your best defense against this kind of chronic, low-grade inflammation.
This lifestyle might include a high-fat low-carb ketogenic diet. Keto helps keep blood sugar low, reduces the NADH:NAD+ ratio, inhibits the inflammasome, and offers a variety of other potential brain benefits.
Here’s the punchline. More research is needed, but right now — keto shows promise for reducing brain inflammation.