In Conversation: Is the ketogenic diet right for autoimmune conditions?

The ketogenic diet is often labelled controversial due to its low carb, high fat nature. However, it is also touted as one of the best diets for weight loss, improving insulin sensitivity, and controlling seizures. But could this diet also have the potential to help inflammatory autoimmune conditions and reduce chronic pain?
Share on Pinterest
The ketogenic diet has been the center of some controversy over the years. It is characterized by a very low consumption of carbohydrates—less than 50 grams a day—offset by a higher proportion of fat. Its opponents often demonize it for cutting out whole food groups while its advocates maintain that its benefits outweigh the risks.
ketogenic diet
carbohydrates
50 grams
higher proportion
However, apart from its well-studied benefits in managing epilepsy in children, evidence for its other potential advantages—such as reducing inflammation—has remained scarce, at least in humans.
managing epilepsy in children
What’s certain for now, however, is that we are still uncovering the exact mechanisms behind why and how this diet works and impacts health.
In the latest installment of our In Conversation podcast, we discuss the benefits and drawbacks of following a ketogenic diet while diving into how the diet may potentially impact autoimmune conditions such as lupus, with Dr. Susan A. Masino of Trinity College, Vernon D. Roosa professor of Applied Science, and author of “Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease” weighing in as an expert, and Shea, who has trialled the diet with his lupus, sharing his personal experience.
In Conversation
Dr. Susan A. Masino
You can listen to this month’s episode below, or on your preferred streaming platform:

How keto came to be
In 2021, the ketogenic diet officially marked its 100th anniversary. In the 1920s, the keto diet was introduced as an alternative therapy to help children with epilepsy after doctors saw that mimicking the metabolism of fasting not only improved symptoms but also helped control seizures.
100th anniversary
control seizures
“[The diet] was used to try and treat epilepsy because it had been observed when people who had seizures didn’t eat [carbohydrates] the seizures would stop. But, of course, that wasn’t sustainable. So, it was sort of developed to try and further explore this therapeutic potential of fasting, in epilepsy. It was effective in adults and children,” said Dr. Masino.
Mimicking ‘starvation’
Keto’s main mechanism of action is via prompting the body to switch into a different energy-forming process—using fat rather than simple carbohydrates (such as glucose and fructose) and complex carbohydrates (such as starch and dietary fibers) as its primary source for fuel.
When the liver starts breaking down fats, it starts producing chemicals called ketones. When the level of ketones in the blood reach the appropriate level, and the body relies on fat, or specifically ketone bodies, for energy, it enters a metabolic state called ketosis.
ketone bodies
ketosis
“[W]hen you have restricted carbohydrates, or just insufficient calories, you will start generating ketone bodies instead of glucose. And so your body will be using these ketones for fuel,” explained Dr. Masino.
calories
The keto diet, in a sense, stresses the body initially, which sparks a protective response much like exercise does to muscles. As a result, it reduces inflammation, oxidative stress, and sensitivity within the nervous system— all of which can help with managing chronic pain.
reduces inflammation
oxidative stress
Dr. Masino underscored that it isn’t always necessarily ‘a stress-inducing state’ for the body when it produces ketones, and evolutionarily, humans have experienced this state quite frequently when there was less available food.
She added that the body can start generating ketones even in “a relatively short duration of insufficient calories or restricted carbohydrates.”
“I think the best way to think about how a ketogenic diet works is that it works in many ways, on many different cellular processes, and tissues in the body. And that makes it difficult to study and nail down what is the mechanism, but also makes it very powerful in that it has a number of different mechanisms.”— Dr. Susan A. Masino
Multiple mechanisms of action
Using food—the fuel we use for many metabolic processes in the body—as potential treatments for metabolic-related disorders or chronic conditions is nothing new.
Dr. Masino elaborated on the multiplicity of mechanisms of the keto diet:
“[It may] address a number of different conditions because it can increase energy production, reduce inflammation. [A] lot of my work has been centered on adenosine, which is a really interesting molecule that is involved in communication between nerve cells—it’s involved in energy cycles, it can impact DNA methylation.”
She added that the ketogenic diet increases production of adenosine.
Although many people report rapid weight loss while on a keto diet, the reverse—in less extremes—has also been true.
“[W]hat’s been amazing to me is that this kind of ketone-based metabolism seems to help people who are overweight to lose weight. But it [also] helps people who are underweight or animal models that suffer from underweight to maintain and stabilize their weight. So it’s not always a weight loss diet,” said Dr. Masino.
Dr. Masino believes the keto diet may help restore a state of physiological balance.
“It’s almost something that I think through this multiplicity of mechanisms [that] is helping your body to get to its sort of ideal physiological state, where it is then more resilient to other stresses that may come in on it,” she said.
“[If] you have a more resilient physiology that’s less inflammatory, has great mitochondrial energy production—which the ketogenic diet absolutely does— then you can fend off assaults from all of the things that our bodies are assaulted with.”— Dr. Susan Masino
How the diet may potentially help autoimmune conditions lies in these yet-uncovered mechanisms.
Keto, the microbiome, and inflammatory pain
Interest in the gut microbiome, and how it can influence the body and brain, has been growing over the last few decades.
growing
Previous research has shown that diet can influence inflammatory pain, finding particular links between a Standard American Diet (SAD), which is typically high in processed foods, fats, and carbohydrates, and chronic inflammation.
Previous research
Standard American Diet (SAD)
“[T]he fastest way to change your microbiome is through diet. So it’s not surprising that this would have a rapid effect, and that changes signaling in your brain and in your body,” said Dr. Masino.
Her research, for example, was based on the hypothesis that ketone-based metabolism could increase adenosine— a molecule that could be instrumental in the body’s inflammatory response.
“[A]denosine is also released during any kind of injury or wound during that inflammatory process. And that’s something that can help with the healing. It’s [a] very powerful anti-convulsant molecule,” she elaborated.
She hypothesized that the keto diet could be a way to promote the neuroprotective and anti-seizure benefits of this molecule, which could help regulate the nervous system.
“There’s a lot of interest now in trying to use these metabolic approaches, particularly ketogenic approaches in mental illness, which are all of our neurological disorders are associated with a metabolic and inflammatory component,” she added.
As for keto’s inflammation-reducing benefits, Dr. Masino elaborated on the mechanism:
“Inflammation itself is something that can cause pain. So reducing the inflammation in general, so that it’s not chronic or inappropriate, is itself a critical kind of pain disorder benefit of the ketogenic diet.”
“More specifically, if we increase adenosine in the central nervous system, that means the brain and the spinal cord—if the ketogenic diet is able to do that—that helps calm down the nerve cells directly so that they’re not firing and sending that pain signal.”— Dr. Susan Masino
“If you have better metabolism, if your mitochondria are in good shape, that helps to clean up all the broken things and keep your cells functioning and able to recover at a cellular level. If we can reduce the pro inflammatory cytokines, that is another important mechanism,” she added.
Another way a ketogenic diet may help calm down chronic pain arising from an overexcited and overstimulated nervous system is via ketones.
One ketone, called Beta-hydroxybutyrate, can block the immune system receptors linked to inflammation, and help decrease nervous system activity.
Beta-hydroxybutyrate
However, it remains unclear whether such ketone bodies produced in a ketogenic diet are essential for mediating pain and inflammatory responses, or whether following a low-glucose diet could also produce similar results.
“[I]n some specific pain conditions, or epilepsy conditions or inflammatory conditions, maybe the ketone bodies are critical in that case, and in other cases, maybe just reducing and stabilizing glucose is enough to relieve those symptoms,” said Dr. Masino.
Addressing controversies on keto
The low fiber, high fat content of the keto diet, as well as its effects on weight and its sustainability in the long term have been the main areas of concern.
One particular area of controversy for keto is its high fat content—both in saturated and unsaturated fats.
“[This] has been related to changes in dietary recommendations, where fat was basically vilified and became another focus of changing our food system so that we eat less fat and less saturated fat. So [the ketogenic diet] became not only perceived as less scientific, but actually dangerous to eat this much fat,” explained Dr. Masino.
High fat diets aren’t necessarily bad, stressed Dr. Masino.
“It’s really high fat diets in combination with carbohydrates that have those toxic effects,” she said.
Dr. Hilary Guite pointed out the main problem many people have when following a diet higher in fat.
“[If] you have a high fat diet, in the face of low carbs, your body reacts very differently to the fat. It starts using them. Whereas if you have a standard American diet, then you’re having high fat and high carbs. And that’s where the danger from fats coming,” she said.
Dr. Masino agreed.
“[T]hat’s exactly the issue. [It is a] completely different environment with high fat and restricted carbohydrate versus high fat and high carbohydrate, which is the environment that most of us are physiologically, in most of the time, which is much more pro inflammatory, will cause you to gain weight. [W]hereas [with] high fat, low carb, you’re not putting on weight, you’re maintaining your weight,” she said.
Keto’s impact on lipids because of its high saturated fat content has been another aspect deemed controversial. Consuming saturated fats, which are found in butter, cheese, and fatty meats, has been linked to higher total and low-density lipoprotein cholesterol (LDL-C) levels, which can increase the risk for heart attack and stroke.
higher total and low-density lipoprotein cholesterol (LDL-C) levels
heart attack
stroke
However, it appears that high saturated fat diets increase the larger buoyant sub fraction of LDL-C (which have not been associated with increased cardiovascular disease). Furthermore a keto diet results in decreases in the small dense sub fraction of LDL-C, high levels of which have been associated with increased heart attack and stroke.
increase the larger buoyant sub fraction of LDL-C
However, there is conflicting evidence in the literature about keto’s impact on cholesterol and cardiovascular disease, and can lead to alarming rises of LDL-C though case studies like this do not distinguish the type of LDL-C.
conflicting evidence
“[T]here has been a concern that if the diet increases your cholesterol levels, [then] that would be a hallmark for cardio metabolic problem[s]. I think we need to reevaluate the mantra that cholesterol is the villain in terms of cardio metabolic issues,” said Dr. Masino.
Dr. Guite, meanwhile, expressed concern about the health of the gut microbiome while on the keto diet. She said recent research has indicated that children on long-term ketogenic diets had lower levels of gut bacteria that protect the gut lining.
recent research
“[I]f you take away those legumes and the high fiber foods, then the bacteria can start using the mucus around the lining and actually damage the gut [in the] long term. What do you think the impact of a long term ketogenic diet is on the gut microbiome and the integrity of the gut lining?” asked Dr. Guite.
Dr. Masino acknowledged that, especially in the absence of a trained dietician, such negative effects may be seen.
“[I] do want to mention that dieticians actually recommend eating prebiotic foods like fermented foods [such as] pickles, sauerkraut. [P]rebiotic foods like that might be really protective against that possible negative consequence,” she said.
There is also research that suggests the ketogenic diet can increase certain types of gut bacteria, such as Akkermansia muciniphila, one of several markers of good metabolic health that occur on the keto diet.
Akkermansia muciniphila
Lived experience: Lupus and keto
To see if the keto diet may actually help improve the management or severity of pain and inflammation-related symptoms, Medical News Today asked Shea, who has lupus, about his experience on-and-off the diet over the years.
Shea first described how he felt after his body had switched into a state of ketosis.
“[I initially] had a lot of gastrointestinal problems, [a] bit of stomach gurgling, bloating, [feeling] really, really lethargic. And I didn’t really want to do much, [it] felt like a headache as well. And that lasted for about four or five days,” he said.
headache
These symptoms are more commonly referred to as the “keto flu“.
keto flu
On a more personal level, Shea also shared his struggles with strictly following the diet, especially in social settings.
“[It] was very hard to do in the beginning. Because in the beginning, you just want a cake, cookies, bread, rice, anything. And then you have to realize that those are all things that you can’t really eat,” he said.
Shea said one of the hardest switches he had to do was with snacks because most of them were very high in carbohydrates.
“[So] you have to make your own kind of snack or just have a slice of cheese to hold you down,” he said.
Around the 2-month mark is when Shea grew accustomed to the keto diet and he knew what he could eat.
Although Shea didn’t adopt this diet specifically to see whether it helped with his lupus, he did see positive changes in the management and frequency of his symptoms.
“I didn’t start the diet to help with my autoimmune disease. It was mainly for health. And this was just a side effect of what happened with it,” he explained.
“Before I started the keto diet, I would take about two to three allergy tablets a day. And then when I was on the keto diet, probably at the 2-month mark, I wasn’t taking that many tablets anymore. It was usually about one a day. And it got to the point where I was taking half a tablet a day or I can miss a day and I would still be fine. And the longest I’ve gone is about three days without taking medication.”— Shea, on his experience with lupus and the keto diet
In terms of chronic pain, Shea also saw improvements.
“[W]hen I was on the diet, my pain, I could almost feel that it would reduce the longer I was on it. And it wasn’t as [wide]spread over as it was before. Because before I would feel it in almost all my joints, and it would feel quite stiff,” he said.
“[T]he longer I was on the diet—it wasn’t magically going away, or like I could feel [a] huge change—but there was something there that I could kind of notice where I wasn’t as stiff as before. And my body wasn’t burning as much and in a lot of agony over it.”— Shea, on his experience with lupus and the keto diet
Is keto sustainable?
Dr. Masino reiterated that there are certain situations where it’s a recommended diet, such as in epilepsy. There are also instances where it’s not, which are very easily determined, she said.
But when it comes to long-term concerns, Dr. Masino believes—with the correct guidance—the keto diet can be sustainable.
“There are people that have definitely been following a ketogenic diet for decades and have not had any ill effects. So, I think we need to dispel some of the myths that this is really dangerous, or not sustainable, or not recommended by the medical profession,” she said.
“I would encourage [people] to find a keto-literate provider that could help give them advice or a dietitian,” she advised.
Shea believes, for him, it’s not a diet that he can do in the long term.
“[I]t’s not very sustainable [because] you’re just constantly eating fatty foods. And you will get to the point where you want to go out for a meal with some friends or you want to go on a date or anything like that. And you can’t really get the options for a keto diet out there,” he said.
“[I]f you break the diet, it can have consequences with it almost immediately. When I do come off the diet, I have a huge flare up,” he said. However, he also said that the keto diet brings really fast end results for him.
For now, it seems, keto’s benefits on chronic pain and inflammatory autoimmune conditions remains rather speculative. However, as more evidence surfaces, this approach may prove valuable in treating or complementing existing therapies for such conditions.