A UC Davis study shows that a ketogenic diet slows early Alzheimer’s memory loss in mice through the molecule BHB, offering hope for its application in human aging and cognitive health.
A molecule found in the diet could play a significant role in slowing the progression of Alzheimer’s disease.
A recent study conducted by scientists at the University of California, Davis, reveals that a ketogenic diet can significantly delay the early stages of Alzheimer’s-related memory loss in mice. This early memory loss is comparable to mild cognitive impairment in humans that precedes full-blown Alzheimer’s disease.
The study was published in the Nature Group journal Communications Biology.
The ketogenic diet is a low-carbohydrate, high fat and moderate protein diet, which shifts the body’s metabolism from using glucose as the main fuel source to burning fat and producing ketones for energy. UC Davis researchers previously found that mice lived 13% longer on ketogenic diets.
Slowing Alzheimer’s
The new study, which follows up on that research, found that the molecule beta-hydroxybutyrate, or BHB, plays a pivotal role in preventing early memory decline. It increases almost sevenfold on the ketogenic diet.
“The data support the idea that the ketogenic diet in general, and BHB specifically, delays mild cognitive impairment and it may delay full-blown Alzheimer’s disease,” said co-corresponding author Gino Cortopassi, a biochemist and pharmacologist with the UC Davis School of Veterinary Medicine. “The data clearly don’t support the idea that this is eliminating Alzheimer’s disease entirely.”
Scientists gave mice enough BHB to simulate the benefits of being on the keto diet for seven months.
“We observed amazing abilities of BHB to improve the function of synapses, small structures that connect all nerve cells in the brain. When nerve cells are better connected, the memory problems in mild cognitive impairment are improved,” said co-corresponding author Izumi Maezawa, professor of pathology in the UC Davis School of Medicine.
Cortopassi noted that BHB is also available as a supplement for humans. He said a BHB supplement could likely support memory in mice, but that hasn’t yet been shown.
Other cognitive improvements
Researchers found that the ketogenic diet mice exhibited significant increases in the biochemical pathways related to memory formation. The keto diet also seemed to benefit females more than males and resulted in higher levels of BHB in females.
“If these results translated to humans, that could be interesting since females, especially those bearing the ApoE4 gene variant, are at significantly higher risk for Alzheimer’s,” Cortopassi said.
The research team is optimistic about the potential impact on healthy aging and plans to delve further into the subject with future studies.
Following a ketogenic diet could help stave off Alzheimer’s, research suggests. Clique Images/Stocksy
A ketogenic (keto) diet can slow the arrival of the mild cognitive loss that signals the development of Alzheimer’s disease, a new study in mice suggests.
The authors of the study found that a low-carb, high-fat keto diet results in an increase in BHB molecules that have been associated with protection against neuroinflammation.
Experts have expressed a need for confirmatory support in humans, particularly since “Alzheimer’s disease” in mice does not fully replicate the human version.
In a new study using a mouse model, a ketogenic (keto) diet postponed the onset of Alzheimer’s disease (AD).
Delaying Alzheimer’s is being credited with a sevenfold increase in the mice’s levels of the beta-hydroxybutyrate (BHB) molecule.
The BHB molecule has been associated with delays in the onset of mild cognitive dementia typical of the early stages of Alzheimer’s. The moleculeTrusted Source is also found in humans, where it’s produced when the body burns fat for energy in order to feed the body’s mitochondriaTrusted Source. The molecule supports the transfer of energy from the liver to the rest of the body when glucose levels are insufficient.
The authors of the study from the University of California, Davis (UC Davis) have previously published researchTrusted Source finding that BHB, depending on dosage, is anti-inflammatory for human brain cells inflamed by beta-amyloid plaques.
These plaques were, for a time, considered the main cause of Alzheimer’s. Yet, many people have the plaques who never develop Alzheimer’s.
The new study involved genetically modified APP/PS1 mice who express a mouse/human amyloid precursor protein as well as a mutant human presenilin 1 gene. Both target central nervous system neurons.
The mice were bred at UC Davis. Their female and male offspring lived in a 12-hour light and 12-hour dark environment, with up to four mice in a cage eating a standard mouse chow diet for six months. At that age, they were assigned to weight-balanced groups, with each mouse living in a separate enclosure for the remainder of the study, so researchers could control their consumption of food.
Mice were given either a keto diet or a carbohydrate-rich standard diet — both diets provided the same number of calories.
The researchers observed that female mice had higher levels of BHB in their bodies than males, as well as brain enzymes known to support memory.
At the same time, male mice who were switched to a late-midlife keto diet exhibited improved spatial memory.
Michelle Routhenstein, registered dietician and nutritionist at EntirelyNourished.com, who was not involved in the study, explained that “A ketogenic diet is a high fat, low-carbohydrate eating approach that causes ketosis.”
“Ketosis is a metabolic state where the body primarily burns fat for fuel instead of carbohydrates, which yields ketone bodies as an alternative energy source,” she continued.
One concern regarding the higher levels of fat in a keto diet is the promotion of neuroinflammation that can adversely affect cognitive health. However, more of the right fats can reduce neuroinflammation.
Indeed, in the study, lead author Dr. Gino A. Cortopassi told Medical News Today that “When the exact same number of calories are delivered by keto as by the control diet, there is a significant reduction of systemic inflammatory cytokinesTrusted Source.”
“There are neuroprotective elements found in certain fats, like omega-3 fatty acids, fat-soluble carotenoids, and vitamins, which can help combat inflammation and oxidative stress,” Routhenstein noted.
On the other hand, Routhenstein said, “While some fat in the diet is helpful to reduce inflammation and neuroinflammation, excessive intake of saturated fats could potentially elevate cholesterol levels and cardiovascular risk.”
“Long-term adherence [to a keto diet] may also lead to nutrient deficiencies and adverse effects on heart and gut health, necessitating careful monitoring and balanced nutrition to mitigate potential harms.” — Michelle Routhenstein
As a cardiovascular dietician, Routhenstein does not recommend a strict keto diet.
Dr. Cortopassi explained how BHB levels increase in humans, saying “After humans have fasted for about 12 hours, BHB levels rise. This is because the carbohydrate stores have become exhausted.”
He added that humans on a keto diet have significantly higher levels of BHB than humans on a standard, carb-rich, diet.
Dr. Cortopassi said human BHB levels may be increased in any of three ways.
First, obviously, is going on a keto diet. Second, one may take a BHB supplement. Third, and least effective, he said, is putting oneself on a one-meal-a-day carbohydrate diet — in which BHB levels will slowly rise after the liver’s glycogen is depleted. However, BHB levels will drop “precipitously” when the next carbohydrate meal is consumed.
Before making any significant dietary changes, it is best to consult your physician.
“It is very important to recognize that this was a study in mice and does not provide any conclusive evidence of ketogenic diet and Alzheimer’s progression in humans,” said Routhenstein.
Dr. Stefania Forner,Ph.D., Alzheimer’s Association director of medical and scientific relations, who was also not involved in the study, agreed.
“This study is based on research in a mouse model of Alzheimer’s. While animal models of the disease are somewhat similar to how Alzheimer’s progresses in humans, they do not replicate the disease in humans exactly. Models are important in helping us understand the basic biology of the disease, but we need human studies in representative populations for ideas to be fully validated.” — Dr. Stefania Forner
While the new study presents “intriguing” findings, Dr. Forner felt “more research is needed to understand the impacts and outcomes of a ketogenic diet on people living with, or at risk for, Alzheimer’s.”
Dr. Forner made clear, however, that, “At this point, no one should adopt this diet to prevent or treat Alzheimer’s or other cognitive impairment. If you are considering changing your diet for this purpose, always talk to your healthcare provider first.”
In 2025, the Alzheimer’s Association expects to publish the results of their U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER). This is a two-year clinical trial involving a large representative group of Americans.
Dr. Forner said it is investigating whether “lifestyle interventions that simultaneously target many risk factors — including diet — can protect cognitive function in older adults who are at increased risk for cognitive decline.”
Summary: A ketogenic diet significantly postpones the onset of Alzheimer’s-related memory decline in mice, a phase akin to human mild cognitive impairment preceding Alzheimer’s disease. Key findings highlight the molecule beta-hydroxybutyrate (BHB) as instrumental in this protective effect, showing a nearly seven-fold increase in mice on the diet and improving synaptic function critical for memory.
While the study indicates that the diet, particularly BHB, doesn’t eliminate Alzheimer’s, it suggests potential for delaying its early stages. Additionally, the research noted more pronounced benefits in female mice, pointing to intriguing implications for human health, especially among women at higher risk for Alzheimer’s.
Key Facts:
Ketogenic Diet’s Protective Role: The ketogenic diet boosts levels of BHB in the body, which is linked to delaying the early stages of Alzheimer’s-related memory loss in mice.
Gender-Specific Benefits: The ketogenic diet was found to be more beneficial for female mice, indicating a potential for greater impact on women, particularly those with the ApoE4 gene variant linked to higher Alzheimer’s risk.
Future Research Directions: The findings open new avenues for research into healthy aging and Alzheimer’s prevention, with an emphasis on further exploring the effects of BHB supplementation and the ketogenic diet’s neuroprotective mechanisms.
Source: UC Davis
A new study from researchers at the University of California, Davis, shows a ketogenic diet significantly delays the early stages of Alzheimer’s-related memory loss in mice. This early memory loss is comparable to mild cognitive impairment in humans that precedes full-blown Alzheimer’s disease.
The study was published in the Nature Group journal Communications Biology.
The research team is optimistic about the potential impact on healthy aging and plans to delve further into the subject with future studies.
The ketogenic diet is a low-carbohydrate, high fat and moderate protein diet, which shifts the body’s metabolism from using glucose as the main fuel source to burning fat and producing ketones for energy. UC Davis researchers previously found that mice lived 13% longer on ketogenic diets.
Slowing Alzheimer’s
The new study, which follows up on that research, found that the molecule beta-hydroxybutyrate, or BHB, plays a pivotal role in preventing early memory decline. It increases almost seven-fold on the ketogenic diet.
“The data support the idea that the ketogenic diet in general, and BHB specifically, delays mild cognitive impairment and it may delay full blown Alzheimer’s disease,” said co-corresponding author Gino Cortopassi, a biochemist and pharmacologist with the UC Davis School of Veterinary Medicine.
“The data clearly don’t support the idea that this is eliminating Alzheimer’s disease entirely.”
Scientists gave mice enough BHB to simulate the benefits of being on the keto diet for seven months.
“We observed amazing abilities of BHB to improve the function of synapses, small structures that connect all nerve cells in the brain. When nerve cells are better connected, the memory problems in mild cognitive impairment are improved,” said co-corresponding author Izumi Maezawa, professor of pathology in the UC Davis School of Medicine.
Cortopassi noted that BHB is also available as a supplement for humans. He said a BHB supplement could likely support memory in mice, but that hasn’t yet been shown.
Other cognitive improvements
Researchers found that the ketogenic diet mice exhibited significant increases in the biochemical pathways related to memory formation. The keto diet also seemed to benefit females more than males and resulted in a higher levels of BHB in females.
“If these results translated to humans, that could be interesting since females, especially those bearing the ApoE4 gene variant, are at significantly higher risk for Alzheimer’s,” Cortopassi said.
The research team is optimistic about the potential impact on healthy aging and plans to delve further into the subject with future studies.
Funding: The study was funded by the National Institute on Aging, a unit of the National Institutes of Health.
Other authors include Jacopo Di Lucente and Lee-Way Jin with the Department of Pathology and the MIND Institute at UC Davis Health; John Ramsey, Zeyu Zhou, Jennifer Rutkowsky, Claire Montgomery and Alexi Tomilov with the School of Veterinary Medicine; Kyoungmi Kim with the Department of Public Health Sciences at UC Davis Health; Giuseppe Persico with the European Institute of Oncology, IRCCS; and Marco Giorgio with the University of Padova.
Abstract
Ketogenic diet and BHB rescue the fall of long-term potentiation in an Alzheimer’s mouse model and stimulates synaptic plasticity pathway enzymes
The Ketogenic Diet (KD) improves memory and longevity in aged C57BL/6 mice. We tested 7 months KD vs. control diet (CD) in the mouse Alzheimer’s Disease (AD) model APP/PS1.
KD significantly rescued Long-Term-Potentiation (LTP) to wild-type levels, not by changing Amyloid-β (Aβ) levels. KD’s ‘main actor’ is thought to be Beta-Hydroxy-butyrate (BHB) whose levels rose significantly in KD vs. CD mice, and BHB itself significantly rescued LTP in APP/PS1 hippocampi. KD’s 6 most significant pathways induced in brains by RNAseq all related to Synaptic Plasticity.
KD induced significant increases in synaptic plasticity enzymes p-ERK and p-CREB in both sexes, and of brain-derived neurotrophic factor (BDNF) in APP/PS1 females.
We suggest KD rescues LTP through BHB’s enhancement of synaptic plasticity. LTP falls in Mild-Cognitive Impairment (MCI) of human AD. KD and BHB, because they are an approved diet and supplement respectively, may be most therapeutically and translationally relevant to the MCI phase of Alzheimer’s Disease.
From navigating the keto flu to stocking up on ketogenic diet foods, here are science-backed answers to some of the most common keto questions
Foods that are high in fat and low in carbs are fair game on the keto diet.
When it seems like everyone — not just celebrities — has tried the ketogenic diet, you may want to know if it’ll work for you. The so-called keto diet is a high-fat, moderate-protein, very low-carb eating plan. But while people say that you can eat all the butter and bacon you want and still lose weight, is it really true — or healthy, for that matter? Is the keto diet actually the best way to lose weight? Or can it cause more problems than it solves? Here are your top keto questions, answered.
5 Myths About the Keto Diet
1. Is the Keto Diet Healthy?
The keto diet originated as a therapeutic diet used to control seizures in people who have epilepsy, according to the Epilepsy Foundation. For those people, a keto diet may be necessary for their health. But most people certainly don’t have to go on the keto diet in order to be healthy.
Today, the diet has become trendy, and many people are using it to lose weight. However, eating high levels of saturated fat may pose a risk for long-term heart health — and in the short term, severely low carb diets may come with unpleasant side effects, like constipation and headaches, notes the Mayo Clinic. Given the restrictive nature of keto (it eliminates most fruit and dairy, whole grains, many vegetables, and legumes), you may also fall short in terms of certain nutrients, like fiber.
2. Is the Keto Diet Safe to Follow?
Even though following an extremely high-fat diet can feel like a radical way to eat, “the research looking at ketosis via diet has not shown any real negative consequences when done in the short term,” says Scott Keatley, RDN, of Keatley Medical Nutrition Therapy in New York City. (Ketosis is the natural metabolic state in which your body is burning fat instead of its usual fuel source, glucose, which is a kind of sugar.)
But there have been few long-term studies, adds Kendra Whitmire, CNS, who practices functional and therapeutic nutrition in Laguna Beach, California. It’s difficult to definitively say that it’s safe, and it also largely depends on the types of foods you’re eating on the diet. (For instance, olive oil is a healthier choice than butter; salmon is healthier than bacon.) That said, following the keto diet properly, and particularly with help from a medical professional, should reduce negative health effects, says Whitmire.
3. Is Ketosis Bad?
Typically, your body breaks down carbohydrates as its preferred fuel source. Ketosis is when your body has switched into a fat-burning state and breaks down fat into ketone bodies that are used as energy. Beyond the keto flu, “many studies have shown that entering ketosis via diet does not have any real negative consequence in the short term,” says Keatley. But long-term studies are needed to truly assess the impact, he adds. Bottom line: Putting your body into ketosis for a limited time is likely not harmful for most healthy people.
4. How Many Carbs Do You Actually Eat on a Keto Diet?
A keto diet is generally made up of 70 to 75 percent fat, 20 to 25 percent protein, and 5 to 10 percent carbohydrates, says Jill Keene, RDN, a registered dietitian nutritionist in private practice in White Plains, New York. The exact number of grams (g) of carbohydrates will be different for everyone, but it is generally around 20 to 50 g per day. Many people on a keto diet count “net carbs,” which is total carbs minus fiber. Fiber isn’t “counted” in the carbohydrate total because it doesn’t get digested by the human body. Either way, that number of carbs is very low and requires careful planning. Eating a little fruit, starchy vegetables, sugary foods, or whole grains can easily kick you out of ketosis.
5. Can You Drink Alcohol on the Keto Diet?
Yes. “Even though there are often carbs in alcohol, you can still drink it in limited amounts,” says Keatley. Realize that on days when you do choose to consume alcohol, you may have to adjust your carbs from other sources, depending on the kind of alcohol you have. That may mean making tough decisions, like having a drink but skipping a small amount of fruit or Greek yogurt.
Spirits (enjoyed straight, without mixers) tend to be the most keto-friendly alcohol, followed by wine. You may want to halve your usual serving, says Keatley. Beer and wine can eat up a lot of your carbs, and they don’t give back in terms of vitamins and minerals. “It’s a waste of your carbs,” he says.
Here’s what each alcoholic drink contains, carb-wise, according to the U.S. Department of Agriculture (USDA):
There’s no doubt that a ketogenic diet may help spur weight loss, at least initially — and anecdotal reports of drastic transformations are easy to find. “I have clients who have lost a significant amount of weight on a keto diet, but they were obese when starting and had quite a bit of fat to lose. These individuals can have fairly drastic body transformations,” says Keatley.
In a study published in 2017 in the Journal of Clinical Endocrinology, 20 people with obesity who followed a very low-calorie keto diet for four months lost an average of 44 pounds, mainly from body and visceral fat. (It’s important to note that there was no placebo group and this was a small sample source, so the findings are limited, and the diet followed included just 600 to 800 daily calories, which is well below what most health professionals recommend.) In another study published in 2017, in Nutrition Metabolism, normal-weight adults who followed a non–energy (calorie) restricted keto diet for six weeks lost about 4 pounds in both fat and lean body mass.
But long-term studies show that there’s not much of a difference in weight loss between keto and other diets. A past meta-analysis compared adults on a ketogenic diet (eating less than 50 g of carbs) with those on a conventional low-fat diet. After at least a year, those on the keto diet lost an additional two pounds, compared with the group that slashed fat. The bottom line is that many diets, including keto, may help you lose the same amount of weight in the long run. With that news, know that there may be a better option out there for you, says Keatley.
7. What Fruits Can I Eat on the Ketogenic Diet?
Fruit is generally not a mainstay of the keto diet. With so much natural sugar, fruit generally has too many carbs to be included. But you can have small amounts of lower-carb fruits, like berries, says Whitmire. And if you’re really getting technical, avocado and coconut, two higher-fat foods, are, in fact, fruits. Based on USDA carb counts*, here are the fruits that can work on a keto eating plan:
*All carb values are net carbs, which is total carbs minus fiber. Fiber is often not counted in net carb totals, as the nutrient doesn’t get digested.
8. Can I Eat Snacks Like Popcorn, Oatmeal, and Yogurt on Keto?
Unfortunately, high-carb foods like popcorn or oatmeal probably won’t fit in the keto diet. One cup of air-popped popcorn contains 5 g of net carbs, per USDA data, which may be a quarter of your carb allotment for the entire day. It’s also worth mentioning that 1 cup of popcorn is not a large serving; it contains just 30 calories and no fat, so it won’t be filling. Oatmeal likely doesn’t fit either. About a quarter cup of plain dried oats (about half a cup cooked, also a small portion) has 12 grams of net carbohydrates for 77 calories and just 1 gram of fat, per the USDA. As for yogurt, it depends on what type you choose and whether it’s keto-compliant. One 5.3-ounce container of Fage plain 5 percent milk fat Greek yogurt, for instance, contains 5 g of carbohydrates. Remember to choose plain versions, as flavored ones will add more sugar (and, therefore, carbs).
Better keto-compliant snacks include nuts (1 ounce of almonds has 3 g net carbs, per USDA data), seeds (half a cup of sunflower seed kernels has 3 g of net carbs), and small amounts of low-carb fruits like berries, says Whitmire. Beef jerky and nonstarchy veggies such as broccoli and cucumbers are other good snack options on keto.
9. Should I Be Concerned About the Keto Flu?
If you’re interested in the keto diet, you have probably read about the keto flu, one not-so-fun side effect. “The keto flu is definitely real,” says Keatley. “Your body functions really well on carbohydrates — that’s what it was designed for. When it switches to fat burning, it becomes less efficient at making energy,” he says. On keto, you have less energy available and you may feel sick and sluggish, kind of as if you have the flu. As your body naturally adjusts to this new way of drawing energy, you will come out of it. This may take a couple of weeks, says Keatley.
10. Will the Keto Diet Give Me Kidney Stones?
“Consuming high levels of red meat and not drinking a lot of water may make stones more likely,” says Whitmire. She adds that on a keto diet, you need to stay hydrated and replenish electrolytes (minerals like sodium, potassium, magnesium, and calcium). “If not, this can increase your risk of side effects like stones,” she says. Past research gives a small glimpse into how likely kidney stones may be. A systematic review and meta-analysis published in 2021 in Diseases found that adults who follow the keto diet have a slightly elevated risk of developing kidney stones. If you have risk factors, like a family or personal history of stones, talk to your doctor about any precautions you should take when on the keto diet.
11. How Might the Keto Diet Affect My Period?
There’s a possibility you may see a change in menstruation. “Studies on younger women who eat severely low-carb for an extended period of time end up with irregular periods or missed periods,” explains Whitmire. Severely limiting carbohydrates may be taxing on the adrenal system, leading to hormonal imbalances that disrupt a woman’s cycle. Similarly, rapid weight loss can also have this effect. The takeaway? “Women may need more carbs on a keto diet compared to men, especially if a woman is noticing a change in her cycle,” she adds.
On the other side of the spectrum, there is limited evidence that for women with polycystic ovary syndrome (PCOS), a ketogenic diet may improve their hormonal balance. A small study, published in Nutrition & Metabolism, found that a small group of women with PCOS who followed a keto diet for 24 weeks lost 12 percent of their body weight and reduced testosterone and insulin levels. Again, talk to your doctor, especially if you’re using the diet as part of your treatment.
12. How Long Do You Need to Stay on the Keto Diet to Lose Weight?
Anecdotally, many people report losing weight quickly on a keto diet, says Keatley. Research in the Journal of Clinical Endocrinology found that obese dieters lost an average of 44 pounds over four months when following a very low-calorie keto diet. That said, Keatley suggests to clients that they spend no more than 12 weeks in ketosis because of the uncertainties of following it long-term and the risk of developing nutritional deficiencies.
When people go off a keto diet and begin to incorporate more carbs into their day, they tend to regain some weight during the adjustment period, he says. They also stand to regain all the weight they lost, and potentially more, if they return to their pre-keto ways of eating after feeling deprived on the plan.
13. How Will the Keto Diet Affect Your Cholesterol Levels?
The interesting thing about a keto diet is that it often leads to weight loss, something that by itself can improve blood lipid levels. At the same time, you may be consuming more saturated fat than ever, in the form of butter, bacon, cream, and coconut oil.
We’ve long been warned that eating excess saturated fat can raise cholesterol and thus put us at risk of heart disease. For that reason, many experts express concern that increased fat intake may be especially harmful for people who already have heart disease or have risk factors for it.
A small study of obese patients on a keto diet found that after 24 weeks, total cholesterol levels dropped, while “bad” LDL cholesterol decreased and “good” HDL cholesterol increased. That could be reflective of the fact that any weight loss, no matter how it is achieved, tends to lower cholesterol. Also, as already mentioned, people who have risk factors for heart disease need to consult their doctors before attempting a keto diet. Past research has concluded that a diet low in carbs but high in fat and protein impaired arterial function in those who were at risk of cardiovascular disease.
What it may come down to is what type of fat you’re consuming on keto. A review and meta-analysis looked at the effect of a low-fat diet versus a low-carb diet on blood lipids. While lower intakes of saturated fat were associated with lower cholesterol levels, higher intakes of monounsaturated fat (like olive oil or avocado) in the context of a high-fat diet were associated with increased levels of heart-protective HDL cholesterol.
14. How Much Protein Will You Eat on the Keto Diet?
A typical keto diet may include 20 to 25 percent of calories coming from protein, says Keene. One common misconception is that this is a high-protein diet, when in reality it’s moderate in protein. “Too much protein can be converted and broken down as sugar to be utilized as an energy source,” she says. That will kick the body out of ketosis.
That said, you don’t want to go too low in protein. “You want to be able to stay in ketosis without sacrificing lean body mass (muscle) if you lose weight,” says Whitmire. This can loosely equate to 1.2 to 1.5 g of protein per kilogram of body weight. (The recommended daily allowance is currently 0.8 g per kilogram of body weight, according to Harvard Health Publishing.) Therefore, a 140-pound woman may aim for 76 to 95 g per day. For reference, a 3-ounce chicken breast offers 26 g of protein, according to the USDA.
One of the best sources of protein on a keto diet is fatty fish (like salmon or mackerel), says Keene, as it offers a source of heart-healthy protein and omega-3 fatty acids. Eggs are another good choice; one large egg contains 6 g of protein and 5 g of fat.
While a keto diet may focus on fat, that doesn’t mean you have to eat bacon and sausages all day. There is room for leaner proteins, like chicken or cod; just remember to add fat (for example, roast the chicken with olive oil) to these lower-in-fat sources, she says. Many cuts of beef are also considered lean or extra lean, as they contain 10 g or less of total fat, as well as a modest amount of saturated fat (4.5 g and 2 g or less, respectively). These include eye of round roast and steak, sirloin tip side steak, top round roast and steak, bottom round roast and steak, and top sirloin steak, notes the Mayo Clinic.
15. Can the Keto Diet Reverse Type 2 Diabetes?
“Though this isn’t the first tool I’d use to help someone control their insulin — carb counting, evenly distributing carbs throughout the day, may be easier to commit to — it’s not off the table, especially with stronger emerging research,” says Keene.
It’s true: Some preliminary research suggests keto may be a good approach for some people with type 2 diabetes. For example, a small study published in 2017 in the Journal of Medical Internet Research randomized overweight adults with type 2 diabetes into two groups: one that consumed a keto diet, and a control group that ate a low-fat diet recommended by the American Diabetes Association. After 32 weeks, the keto group saw their A1C (a measure of average blood sugar over a three-month span) fall more, compared with the control group, and half lowered their A1C to less than 6.5 percent (less than 5.7 percent is considered normal). The keto group also lost 28 pounds, compared with about 7 pounds for the control group.
But larger and longer-term studies are needed, and keto can pose health risks to people with diabetes, especially if you’re following it without supervision from a medical professional. Importantly, anyone who is on medication to lower blood sugar or who is using insulin should be aware that drastically cutting carbs, as you must do on keto, can lead to dangerously low blood sugar, research shows. Unaddressed, this condition, called hypoglycemia, may lead to seizures, loss of consciousness, and blurred vision, according to the Mayo Clinic. (People with type 1 diabetes should not try the keto diet, experts warn.)
The takeaway? Be sure to work with your doctor if you have type 2 diabetes, and manage your expectations. Not only is there no consensus about whether keto is an effective diet approach for diabetes, it’s also tough to stick with, according to research published in the European Journal of Nutrition in 2018. Keep in mind that type 2 diabetes cannot be reversed, but it can be put into remission.
Iain Campbell, a researcher in Scotland, has lived with bipolar disorder since he was young. After trying the ketogenic diet, he discovered profound improvements in his symptoms — and now wants to learn if it can do the same for others. He shared his recent findings at the Metabolic Health Summit in Clearwater, Fla., on Jan. 25.
Iain Campbell was gazing out the bus window on his way to work when he first sensed something radical was reshaping how he experienced the world.
The inkling emerged from an altogether ordinary observation: He felt peaceful, maybe even happy as he watched the trees along the road pass by.
“I hadn’t experienced that in a really long time, probably since I was a kid,” says Campbell, who lives in Edinburgh, Scotland.
“I didn’t know what was going on at the time, but I thought this might be what it feels like to be normal.”
Campbell had lived with bipolar disorder for much of his life. Mental illness runs in his family, and he’d lost loved ones to suicide. Over the years, he tried different treatments, but it had become “increasingly difficult to live with.”
What had changed? A few weeks earlier, he’d started a new diet.
Campbell dealt with unwanted weight gain and metabolic troubles, a common side effect of psychiatric medications.
In an effort to lose weight, he drastically cut back on carbs and instead focused on protein and fat. It turns out he’d unknowingly entered ketosis: A metabolic state where the body switches from glucose as its primary energy source to ketones, which come from fat.
He started learning about the ketogenic diet, which is high fat and very low carb, on podcasts and YouTube videos. Soon, he was tracking his ketone levels, courtesy of an at-home blood test.
“I realized it was actually the ketone level that was making this shift in my symptoms in a way that nothing else ever had,” he says. “It struck me as really significant, like life-changing.”
A career-launching moment
How exactly was a diet performing this alchemy? Campbell decided to pursue a Ph.D. in mental health at the University of Edinburgh, hoping to do his own research and learn whether it could help others.
In online forums, people with bipolar disorder were sharing similar anecdotes — they were finding improvements in their mood, increased clarity and fewer episodes of depression.
But as Campbell searched for ways to launch a proper clinical trial to test the diet’s effectiveness, he became discouraged.
“It was really like you were considered wacky,” he says. “At one point, I thought nobody’s going to pay for this research.”
He put together a 45-minute video summing up the biological rationale for using the ketogenic diet in bipolar disorder and posted it on social media, not expecting much after that.
The ketogenic diet avoids most carbs and instead focuses on high-fat foods, proteins and vegetables.
But some doctors had already started researching it after seeing the potential in their practice, among them Chris Palmer, a psychiatrist at Harvard Medical School and McLean Hospital.
Palmer had his own revelation about the diet a few years earlier, which he detailed in a 2017 case report. Two patients with schizo-affective disorder had “truly dramatic, life-changing improvement in their psychotic symptoms,” he says.
In early 2021, he started working with the eldest son of Jan and David Baszucki, a wealthy tech entrepreneur. Their son Matt had bipolar disorder and had been on many medications in recent years.
Jan Baszucki enlisted Palmer’s help as her son gave the ketogenic diet a try.
“Within a couple of months, we saw a dramatic change,” she says.
Inspired, she started contacting clinicians and researchers, looking to bring more visibility — and funding — to the treatment. Since rigorous data on the diet is still lacking, she wants to see researchers conduct large clinical trials to back up anecdotes like her son’s recovery.
Soon a big-time philanthropist was in touch with Campbell, ready to pay for his bipolar study — and others.
Now, around a dozen clinical trials are in the works, testing the diet’s effect on mental illness, most notably for bipolar disorder, schizophrenia and depression, but also for conditions like anorexia, alcoholism and PTSD.
“The research and the clinical interest is suddenly exploding,” says Dr. Georgia Ede, a psychiatrist in Massachusetts, who began using the ketogenic diet in her own practice about a decade ago.
From epilepsy care to the mainstream
The classic ketogenic diet contains an eye-popping amount of fat, roughly 90% of calories coming from that alone. Other versions have come along that dial down the fat and allow more room for protein and slightly more carbohydrates.
Dr. Chris Palmer (left) signs a copy of his book, Brain Energy, for Addanilka Ramos during the Metabolic Health Summit in Clearwater, Fla. Palmer has been researching the keto diet for years.
Serious followers may buy a device to measure ketone levels in their blood, to track whether they’ve entered a range that means they’re experiencing what’s called nutritional ketosis.
The diet’s entrance into the mainstream has fed plenty of debate about its merits, with some medical groups raising concerns. Yet, there’s also growing attention — and clinical trials underway — on its potential, not only for obesity but a variety of other conditions.
“It’s not a fad diet,” says Dr. Shebani Sethi, who’s leading research into the diet’s potential for mental health at Stanford University. “It’s a medical intervention.”
The ketogenic diet was developed over a hundred years ago for pediatric epilepsy and has seen a resurgence in that field over the last three decades.
“It’s a general standard of care for epilepsy,” says Dr. Eric Kossoff, a pediatric neurologist at Johns Hopkins University.
This track record in epilepsy, the thinking goes, paves the way for its adoption in psychiatry. There are links between the conditions. Medications developed for seizures are regularly prescribed for a range of psychiatric conditions such as bipolar disorder.
“We use them off label, even when we don’t have studies to suggest or prove that they are helpful for people with mental illness,” says Palmer. “So, in many ways, this is nothing new.”
People with psychiatric disorders are at an increased risk. And it’s not just that psychiatric meds can cause weight gain and other issuses. Research shows these problems can arise even before someone with serious mental illness takes medication or is diagnosed.
“We’ve known for a long time that there’s something going on in the metabolism of the brain that’s not quite right in people with severe mental illness,” says Dr. Dost Öngür, chief of the division of Psychotic Disorders at McLean Hospital and a professor at Harvard Medical School.
This evidence of energy problems in the brain and elsewhere in the body has accumulated over the decades in psychiatry — unrelated to the ketogenic diet.
“We can’t say that there’s a causal relationship, but there are a lot of connections that should be explored further,” says Öngür, whose work has focused on this theme in bipolar and schizophrenia.
All of this data is strong enough to suspect that “metabolic problems may be more than just innocent bystanders,” that they may, in fact, play a direct role in the development, severity or course of psychiatric conditions,” says Ede.
Some people use at-home devices to measure ketone levels in the blood to track whether they’ve entered nutritional ketosis.
The theory behind keto’s power
So, how exactly could a diet that stops seizures also exert powerful effects on tough-to-treat psychiatric illness?
Even after decades, scientists who study epilepsy aren’t exactly sure why it works for that illness.
“It’s impacting so many different mechanisms,” says Dominic D’Agostino, a professor of molecular pharmacology and physiology at the University of South Florida who studies the ketogenic diet.
That’s why he likes to characterize the diet as being more like a “shotgun” than a “bullet.”
During ketosis, the body essentially changes metabolic gears. It increasingly draws on ketones — made from the breakdown of fat in the liver – instead of glucose.
“We know this happens on a ketogenic diet,” says Kossoff. “Ketones can be used for energy, but how that helps seizures is the next tricky question.”
Because the diet eliminates carbohydrates, blood sugar comes down and insulin sensitivity improves.
“You take pressure off of your really delicate insulin signaling system,” says Ede, while offering cells another fuel that could bring parts of the “brain back online that may have been stuttering.”
Palmer and other scientists believe problems with mitochondria — the powerhouses of the cells that produce energy — are central to mental illness.
“This is likely due to mitochondria’s essential role in maintaining key brain function,” says Ana Andreazza, a professor of pharmacology and psychiatry at the University of Toronto.
In her lab, Andreazza studies what biological pathways make people with psychiatric illness more vulnerable to mitochondrial dysfunction.
Cumulative damage to these vital powerhouses ultimately leads to a “metabolic shift” that wreaks havoc in myriad ways — what’s apparent in their increased production of lactate.
“The findings are compelling for many psychiatric disorders,” she says.
It’s possible the ketones help the mitochondria by relieving oxidative stress — a harmful buildup of free radicals, she says, and by providing an energy source that circumvents the dysfunctional machinery in the mitochondria.
“Once you trend towards more normal mitochondrial function and metabolic health, that’s restoring neurotransmitter systems, it’s even restoring blood flow to the brain,” says D’Agostino.
Keto diet followers have to get used to embracing larger amounts of fat in their diet. The classic form calls for 90% of calories from fat.
Scientists search for more clues
The effect of ketosis on the mitochondria is one hypothesis for why keto diets could work, but it may not be the whole story.
Much of the data on how the diet affects the brain comes from research into epilepsy and other neurological diseases like Alzheimer’s and Parkinson’s.
Scientists find serious mental illnesses like schizophrenia, major depression and bipolar disorder share notable similarities with these conditions: Inflammation in the brain, oxidative stress, mitochondrial dysfunction, and issues with glucose and insulin.
Research suggests ketosis can be beneficial on these fronts, although human studies are limited. Some of the larger clinical trials now underway for keto diets will seek to pin down what’s going on.
For example, Dr. Deanna Kelly is trying to determine if the diet’s potential benefits emerge from the microbiome in the gut.
“You’re potentially changing the way bacteria are functioning and that could affect your behavior and your brain,” says Kelly, a professor of psychiatry at the University of Maryland School of Medicine, who’s leading an inpatient trial on the ketogenic diet for schizophrenia.
Other scientists are studying the diet’s effect on neurotransmitters like GABA — which acts as a kind of brake in the brain.
Dr. Mary Phillips, who has studied how dopamine affects the reward circuit in bipolar disorder, thinks that may help explain its therapeutic effects.
She hopes her clinical trial of bipolar and the keto diet, which launched recently, also gets at a very practical question:
“How do you know which people the ketogenic diet is going to work for?” says Phillips, a professor of psychiatry at the University of Pittsburgh. “It’s not the easiest diet in the world to get started on.”
Early evidence shows promise
Much of the current evidence on its potential for mental health comes from case reports, observational data and open trials that have laid the groundwork for more rigorous studies.
The research that exists shows improvements in both mental and metabolic health.
Iain Campbell’s small pilot study, designed to test the feasibility of a randomized controlled trial, found patients lost an average of about 10 pounds and had “significant reductions” in blood pressure.
“As the ketone level went up, we saw their mood improved, their energy improved, their anxiety decreased and their impulsivity decreased,” says Campbell, who’s now a Baszucki research fellow in metabolic psychiatry at the University of Edinburgh.
Their blood lactate levels, a sign of mitochondrial dysfunction, dropped as did glutamate in the brain, an effect also seen with anti-seizure medications.
A recent study from Toulouse, France, is the largest to look at hospitalized patients with severe mental illness.
Though three patients couldn’t stick with it, the 28 who did had substantial improvements in their symptoms of depression and psychosis by the third week, says Ede, a co-author of the study.
Ultimately, 43% achieved clinical remission.
There was no control group, but she points out these patients had been hospitalized before under the care of the same psychiatrist — with the only clear difference in treatment this time being the ketogenic diet.
“So we believe the diet probably had something to do with the outcome,” says Ede.
At Stanford, Sethi’s pilot study found the majority of patients with schizophrenia or bipolar disorder had “clinically meaningful improvement” on the diet and close to half “achieved recovery.”
A quarter of those who entered the study had metabolic syndrome — a cluster of risk factors like insulin resistance and high blood pressure — and by the end, had reversed the condition.
Dr. Anissa Abi-Dargham, who isn’t involved in the research, calls the initial data “intriguing,” when considered alongside the existing evidence on epilepsy, and metabolic dysfunction in psychiatric illness.
“All this together convinces me there is a signal that is worth pursuing in a rigorous way,” says Abi-Dargham, chair of the department of psychiatry and behavioral health at Stony Brook University.
But the rush of attention ahead of solid clinical data has raised eyebrows among some psychiatrists.
Dr. Drew Ramsey worries the hype has created an unrealistic perception about the ketogenic diet in mental health. For now, he remains skeptical.
“Does it work? It works for some people, which is awesome, but most things work for some people in mental health,” says Ramsey, a nutritional psychiatrist.
Proponents readily acknowledge the field is still in the early stages.
“You have to be modest about this,” says Öngür. “The ketogenic diet is really a test case, but it’s not the silver bullet.“
Palmer says the diet is a powerful intervention, but “it’s not going to cure everybody with mental illness, or even necessarily help everybody.”
Metabolic psychiatry takes off
The groundswell of excitement around a high-fat, minimal carb diet reflects a broader movement to better recognize the link between metabolic health and mental illness.
Ketogenic diet research is just one branch of a growing area of research now being called metabolic psychiatry.
Dr. Shebani Sethi, a psychiatrist at Stanford, is pioneering research in the field of metabolic psychiatry, including the ketogenic diet’s potential for treating serious mental illness.
Sethi, who coined the term when she launched Stanford’s program in 2015, says the idea is to study how treating metabolic health — tackling conditions like high blood sugar, insulin resistance and obesity — may also improve psychiatric problems.
While keto is the most prominent example, she says medications are also under study, including drugs that make the body more sensitive to insulin — the hormone that helps usher glucose into cells.
This approach is intuitive for Sethi, who trained in obesity medicine and psychiatry. It was in medical school that she first witnessed keto’s potential for her psychiatric patients.
A woman with treatment-resistant schizophrenia had tried the diet to lose weight and manage her diabetes. To her surprise at the time, Sethi recalls it also helped the patient with hallucinations.
A recent clinical trial underscores the promise of targeting metabolic problems, beyond just the ketogenic diet.
Patients with treatment-resistant bipolar depression and insulin resistance, but not Type 2 diabetes, were prescribed the diabetes drug metformin.
By the end of the study, half of those who took the medication had reversed their insulin resistance — and also found dramatic improvements in their psychiatric symptoms, even though most had been ill for 25 years without any remission.
“I was kind of blown away,” says Dr. Cynthia Calkin, a psychiatrist at Dalhousie University in Canada who led the study. “It’s not that metformin is an antidepressant, it’s that it can reverse insulin resistance, and that improves outcomes.”
“A tailwind” to wellness
Neither patients nor clinicians are waiting for the results of larger trials to try keto.
Online, patients share their experiences with — and challenges — trying the diet. And doctors like Sethi and Ede, who trains other clinicians, regularly treat patients with it.
Lori Katz, pictured here with her support dog, started the ketogenic diet under Dr. Sethi’s supervision. She quickly noticed a difference. “It wasn’t just the depressive symptoms, but it was the feeling of lack of control,” she says. The diet “was like a tailwind — just blowing me into a better future.”
About four years ago, Lori Katz ended up at Sethi’s Stanford clinic after trying many treatments for bipolar disorder — a diagnosis she received when she was 18 years old.
She also struggled with chronic pain, binge eating and emotional eating, and unwanted weight gain. Her episodes of depression had led her to consider electroconvulsive therapy (ECT).
The ketogenic diet was quite the adjustment, but Katz gave it a go, under Sethi’s supervision.
“Suddenly, I was losing weight really fast and was extremely satisfied with what I was eating,” says Katz, a dog trainer who lives in Santa Cruz, Calif.
She says those around her quickly noticed a change in her mood.
“It wasn’t just the depressive symptoms, but it was the feeling of lack of control,” she says. The keto diet, she says, “was like a tailwind — just blowing me into a better future.”
Eventually, she started going to the gym and taking longer walks. And after years without a romantic drive, a girlfriend entered her life.
Katz says she can’t always follow the diet perfectly and notices the change in mood when she is less strict. It hasn’t erased the reality of living with a mental illness.
“I will live with this but it’s a question of am I more resilient? Yes. Am I more optimistic? Yes. Am I feeling like I have this tool? Yes, when I get in there and I get the support. I need to stay in ketosis.”
Can it be done?
Indeed, any kind of diet can be hard to stick to, and one that involves largely giving up common comfort foods like bread and sweets may be even more challenging.
About a quarter of those in Campbell’s study withdrew, which he notes is similar to other pilot trials with the ketogenic diet.
Dr. Rif El-Mallakh, a psychiatrist at the University of Louisville, became interested in the diet more than two decades ago and believes it works.
He says he had early success with a few patients, but hasn’t had much luck over the years: “I haven’t been able to get people to stay on it, so I’m not at all as excited as maybe others.”
However, doctors who already use it in their practice say with enough education and support patients can be successful.
Dr. Matt Bernstein has found striking results in some of his patients.
Some opt for the most restrictive form of the diet, especially if they have severe symptoms, but he emphasizes it can be tailored and even a “modest version” has made an “incredible difference” for some patients.
He’ll ease them into it, lowering their carbohydrate intake gradually.
“Some people like to do it cold turkey, but for a lot of people, that’s not the best thing,” says Bernstein, chief medical officer at Ellenhorn, a psychiatric recovery program in Boston.
“The idea is that this is going to be sustainable and not just something you do for a few months and then stop.”
Not many psychiatrists are trained to offer the diet, although the numbers are growing.
Bernstein and other doctors say those with a history of serious mental illness should have medical supervision. There can be lab work and medications that need to be adjusted.
Despite the optimism, there are still many unanswered questions.
In his initial research, Iain Campbell’s already hearing some real results of his dream to help others find this treatment.
“They would describe it to me like, ‘This changed my life completely. I’m reconnecting with my family. I can work again for the first time,'” he says.
Summary: A new study reveals distinct immune system responses to vegan and ketogenic diets. Over a two-week period, 20 participants alternated between these diets, allowing researchers to observe changes in innate and adaptive immunity, metabolic pathways, and gut microbiome.
The vegan diet primarily affected innate immunity and red blood cell pathways, while the keto diet influenced adaptive immunity and a wider range of proteins. These findings highlight the rapid and diverse immune responses to dietary changes, opening avenues for diet-based disease prevention and treatment strategies.
Key Facts:
The vegan diet triggered innate immune responses and affected pathways related to red blood cells, while the keto diet influenced adaptive immunity and a broader range of protein levels.
Both diets significantly altered participants’ microbiomes and metabolic processes.
The study’s controlled environment and diverse participant group demonstrate that dietary changes can consistently affect complex bodily systems.
Source: NIH
Researchers at the National Institutes of Health observed rapid and distinct immune system changes in a small study of people who switched to a vegan or a ketogenic (also called keto) diet. Scientists closely monitored various biological responses of people sequentially eating vegan and keto diets for two weeks, in random order.
They found that the vegan diet prompted responses linked to innate immunity—the body’s non-specific first line of defense against pathogens—while the keto diet prompted responses associated with adaptive immunity—pathogen-specific immunity built through exposures in daily life and vaccination.
The work is published in the journal Nature Medicine.
More study is needed to examine how these nutritional interventions affect specific components of the immune system.
Metabolic changes and shifts in the participants’ microbiomes—communities of bacteria living in the gut—were also observed. More research is needed to determine if these changes are beneficial or detrimental and what effect they could have on nutritional interventions for diseases such as cancer or inflammatory conditions.
Scientific understanding of how different diets impact the human immune system and microbiome is limited. Therapeutic nutritional interventions—which involve changing the diet to improve health—are not well understood, and few studies have directly compared the effects of more than one diet.
The keto diet is a low-carbohydrate diet that is generally high in fat. The vegan diet eliminates animal products and tends to be high in fiber and low in fat.
The study was conducted by researchers from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the Metabolic Clinical Research Unit in the NIH Clinical Center. The 20 participants were diverse with respect to ethnicity, race, gender, body mass index (BMI), and age.
Each person ate as much as desired of one diet (vegan or keto) for two weeks, followed by as much as desired of the other diet for two weeks. People on the vegan diet, which contained about 10% fat and 75% carbohydrates, chose to consume fewer calories than those on the keto diet, which contained about 76% fat and 10% carbohydrates.
Throughout the study period, blood, urine, and stool were collected for analysis. The effects of the diets were examined using a “multi-omics” approach that analyzed multiple data sets to assess the body’s biochemical, cellular, metabolic, and immune responses, as well as changes to the microbiome. Participants remained on site for the entire month-long study, allowing for careful control of the dietary interventions.
Switching exclusively to the study diets caused notable changes in all participants. The vegan diet significantly impacted pathways linked to the innate immune system, including antiviral responses.
On the other hand, the keto diet led to significant increases in biochemical and cellular processes linked to adaptive immunity, such as pathways associated with T and B cells.
The keto diet affected levels of more proteins in the blood plasma than the vegan diet, as well as proteins from a wider range of tissues, such as the blood, brain and bone marrow. The vegan diet promoted more red blood cell-linked pathways, including those involved in heme metabolism, which could be due to the higher iron content of this diet.
Additionally, both diets produced changes in the microbiomes of the participants, causing shifts in the abundance of gut bacterial species that previously had been linked to the diets.
The keto diet was associated with changes in amino acid metabolism—an increase in human metabolic pathways for the production and degradation of amino acids and a reduction in microbial pathways for these processes—which might reflect the higher amounts of protein consumed by people on this diet.
The distinct metabolic and immune system changes caused by the two diets were observed despite the diversity of the participants, which shows that dietary changes consistently affect widespread and interconnected pathways in the body. More study is needed to examine how these nutritional interventions affect specific components of the immune system.
According to the authors, the results of this study demonstrate that the immune system responds surprisingly rapidly to nutritional interventions. The authors suggest that it may be possible to tailor diets to prevent disease or complement disease treatments, such as by slowing processes associated with cancer or neurodegenerative disorders.
Abstract
Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans
Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention on both immunity and the microbiota by performing a post hoc analysis of a clinical trial in which each of the 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks.
Using a multiomics approach including multidimensional flow cytometry, transcriptomic, proteomic, metabolomic and metagenomic datasets, we assessed the impact of each diet, and dietary switch, on host immunity and the microbiota.
Our data revealed that overall, a ketogenic diet was associated with a significant upregulation of pathways and enrichment in cells associated with the adaptive immune system. In contrast, a vegan diet had a significant impact on the innate immune system, including upregulation of pathways associated with antiviral immunity.
Both diets significantly and differentially impacted the microbiome and host-associated amino acid metabolism, with a strong downregulation of most microbial pathways following ketogenic diet compared with baseline and vegan diet.
Despite the diversity of participants, we also observed a tightly connected network between datasets driven by compounds associated with amino acids, lipids and the immune system.
Collectively, this work demonstrates that in diverse participants 2 weeks of controlled dietary intervention is sufficient to significantly and divergently impact host immunity, which could have implications for precision nutritional interventions.
Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.
“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver, Canada.
“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.
Iatan presented the study March 5 at the American College of Cardiology (ACC) Scientific Session/World Congress of Cardiology (WCC) 2023.
The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, Cleveland Clinic, Cleveland, Ohio, warned against paying much attention to the headlines or to the study’s conclusions.
To theheart.org | Medscape Cardiology, Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.”
“The people who were on the ‘keto-like’ diet in this study were different to those who were on the standard diet,” he commented. “Those on the ‘keto-like’ diet were on it for a reason — they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”
He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.”
For the study, Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.
They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.
On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1220 individuals who reported eating a standard diet.
Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs 26.7) and a higher incidence of diabetes (4.9% vs 1.7%).
Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).
Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs 3.64 mmol/L (141 mg/dL) in the standard group (P = .004). Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).
After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.
After adjustment for other risk factors for heart disease — diabetes, hypertension, obesity, and smoking — individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
“Closer Monitoring Needed”
Senior author Liam Brunham, MD, University of British Columbia, commented to theheart.org | Medscape Cardiology: “Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events. This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”
He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.
“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and Apo B and that seems to be driving the risk.”
He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001).
“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”
Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.
“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
Jury Still Out
Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”
Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.
“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Nissen commented.
“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.
New research finds that people on a low-carb, high-fat diet have a higher risk of developing a major cardiovascular event.manusapon kasosod/Moment RF/Getty Images CNN —
A low-carb, high-fat “keto-like” diet may be linked to higher levels of “bad” cholesterol and double the risk of cardiovascular events such as blocked arteries, heart attacks and strokes, according to new research.
“Our study found that regular consumption of a self-reported diet low in carbohydrates and high in fat was associated with increased levels of LDL cholesterol – or “bad” cholesterol – and a higher risk of heart disease,” lead study author Dr. Iulia Iatan with the Healthy Heart Program Prevention Clinic, St. Paul’s Hospital and University of British Columbia’s Centre for Heart Lung Innovation in Vancouver, Canada, said in a news release.
“This study provides an important contribution to the scientific literature, and suggests the harms outweigh the benefits,” said Christopher Gardner, a research professor of medicine at the Stanford Prevention Research Center who has conducted clinical trials on the keto diet. Gardner was not involved in the study.
“Elevated LDL cholesterol should not be dismissed as simply a negligible side effect of a VLCD (very-low-carb diet) or ketogenic diet,” Gardner said, pointing to the higher risk of cardiovascular events in individuals with higher ketone levels in the blood, when compared to those on a more standard diet.
“Our study rationale came from the fact that we would see patients in our cardiovascular prevention clinic with severe hypercholesterolemia following this diet,” Iatan said during a presentation at the session.
Hypercholesterolemia, or high cholesterol, increases a person’s risk of heart attack or other adverse cardiovascular events.
“This led us to wonder about the relationship between these low-carb, high-fat diets, lipid levels and cardiovascular disease. And so, despite this, there’s limited data on this relationship,” she said.
The researchers compared the diets of 305 people eating a LCHF diet with about 1,200 people eating a standard diet, using health information from the United Kingdom database UK Biobank, which followed people for at least a decade.
Researchers found that people following a low-carb, high-fat diet had double the consumption of animal sources compared to those on a standard diet. alex9500/AdobeStock
The researchers found that people on the LCHF diet had higher levels of low-density lipoprotein, also known as LDL, cholesterol and apolipoprotein B. Apolipoprotein B is a protein that coats LDL cholesterol proteins and can predict heart disease better than elevated levels of LDL cholesterol can.
The researchers also noticed that the LCHF diet participants’ total fat intake was higher in saturated fat and had double the consumption of animal sources (33%) compared to those in the control group (16%).
“After an average of 11.8 years of follow-up – and after adjustment for other risk factors for heart disease, such as diabetes, high blood pressure, obesity and smoking – people on an LCHF diet had more than two-times higher risk of having several major cardiovascular events, such as blockages in the arteries that needed to be opened with stenting procedures, heart attack, stroke and peripheral arterial disease,” researchers found, according to the news release.
The researchers said in the release that their study “can only show an association between the diet and an increased risk for major cardiac events, not a causal relationship,” because it was an observational study, but their findings are worth further study, “especially when approximately 1 in 5 Americans report being on a low-carb, keto-like or full keto diet.”
Iatan said the study’s limitations included measurement errors that occur when dietary assessments are self-reported, the study’s small sample size and that most of the participants were British and didn’t include other ethnic groups.
The study also looked at the longitudinal effect of following the diet, whereas most people who follow a keto-like diet tend to follow it intermittently for shorter periods of time.
Most of the participants – 73% – were women, which Iatan said is “quite interesting to see, but it also supports the literature that’s available that women in general tend to follow more dietary patterns, tend to be more interested in changing their lifestyles.”
When asked if there were any groups that were not harmed by following a LCHF diet, Iatan said how long people are on the diet and whether or not they lose weight “can counterbalance any LDL elevation.”
“What matters to remember is that each patient responds differently. And so, there’s really an inter-individual variability between the response. What we found is that, you know, on average, patients tend to increase their LDL cholesterol levels,” she said.
Dr. David Katz, a lifestyle medicine specialist who was not involved in the study, said that “there are various ways to put together a LCHF diet, and it is very unlikely they all have the same effects on serum lipids or cardiac events.”
However, he added, “That a LCHF diet is associated with adverse effects in this study is reality check for those adopting such diets just because they are in vogue.”
Most health experts say the trendy keto diet, which bans carbohydrates to make your body burn fat for fuel, cuts out healthy food such as fruit, beans and legumes, and whole grains. In the keto diet, you limit your intake of carbohydrates to only 20 to 50 a day – the lower, the better. To put that into perspective, a medium banana or apple is around 27 carbohydrates – the full day’s allowance.
“Those food groups that have to be eliminated to achieve ketosis are major sources of fiber in the diet, as well as many important nutrients, phytochemicals, and antioxidants. This is of concern to many health professionals who consider the VLCD or ketogenic diet to be harmful for long-term health,” Gardner said.
Keto is short for ketosis, a metabolic state that occurs when your liver begins to use stored fat to produce ketones for energy. The liver is programmed to do that when your body loses access to its preferred fuel – carbohydrates – and thinks it’s starving.
The keto diet has been around since the 1920s, when a doctor stumbled on it as a way of controlling seizures in children with epilepsy who didn’t respond to other treatment methods.
Low-carb diets like keto rely heavily on fats to fill you up. At least 70% of the keto diet will be made up of fat; some say it’s more like 90%.
While you can get all that fat from healthy unsaturated fats such as avocados, tofu, nuts, seeds and olive oil, the diet also allows saturated fats like lard, butter and coconut oil, as well as whole-fat milk, cheese and mayonnaise. Eating lots of foods high in saturated fat increases the body’s production of LDL cholesterol, which can build up inside the arteries and restrict blood flow to the heart and brain.
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