Researchers have long believed that the keto diet could help reduce an overactive immune system and benefit individuals with conditions such as multiple sclerosis.
Now, they have reason to believe it could be true.
Scientists at UC San Francisco have discovered that the diet makes the gut and its microbes produce two factors that attenuated symptoms of MS in mice.
If the study translates to humans, it points toward a new way of treating MS and other autoimmune disorders with supplements.
The keto diet severely restricts carbohydrate-rich foods like bread, pasta, fruit and sugar but allows unlimited fat consumption.
Without carbohydrates to use as fuel, the body breaks down fat instead, producing compounds called ketone bodies. Ketone bodies provide energy for cells to burn and can change the immune system.
Working with a mouse model of MS, the researchers found that mice who produced more of a particular ketone body, called β-hydroxybutyrate (βHB), had less severe disease.
The additional βHB also prompted the gut bacterium Lactobacillus murinus to produce an indole lactic acid (ILA) metabolite. This blocked the activation of T helper 17 immune cells involved in MS and other autoimmune disorders.
“What was exciting was discovering that we could protect these mice from inflammatory diseases simply by putting them on a diet supplemented with these compounds,” said Peter Turnbaugh, PhD, of the Benioff Center for Microbiome Medicine.
Earlier, Turnbaugh had shown that when secreted by the gut, βHB counteracts immune activation. This prompted a postdoctoral scholar working in his lab, Margaret Alexander, PhD, to see if the compound could ease the symptoms of MS in mice.
In the new study, which appears Nov. 4 in Cell Reports, the team examined how the ketone body-rich diet affected mice unable to produce βHB in their intestines and found that their inflammation was more severe.
However, when the researchers supplemented their diets with βHB, the mice got better.
To find out how βHB affects the gut microbiome, the team isolated bacteria from the guts of three mice fed either the keto diet, a high-fat diet, or the βHB supplemented high-fat diet.
Then, they screened the metabolic products of each group’s distinct microbes in an immune assay and determined that the diet’s positive effects were coming from a member of the Lactobacillus genus: L. murinus.
Two other techniques, genome sequencing and mass spectrometry, confirmed that the L. murinus they found produced indole lactic acid, which is known to affect the immune system.
Finally, the researchers treated the MS mice with either ILA or L. murinus, improving their symptoms.
Turnbaugh cautioned that the supplement approach still needs to be tested in people with autoimmune disorders.
“The big question now is how much of this will translate into actual patients,” he said. “But I think these results provide hope for the development of a more tolerable alternative to helping those people than asking them to stick to a challenging restrictive diet.”
Anti-inflammatory foods can combat disease, researcher says
Almost 60% of Americans have pro-inflammatory diets, increasing the risk of health issues such as heart disease and cancer, according to a recent Omega 3 for chronic pain, by Dr Andrea Furlanstudy utilizing a tool designed to assess inflammation in the diet.
The study also found that specific populations, including Black Americans, men, and people with lower incomes, were more likely to consume a diet high in pro-inflammatory foods.
“Overall, 57% of U.S. adults have a pro-inflammatory diet and that number was higher for Black Americans, men, younger adults and people with lower education and income,” said lead author Rachel Meadows, visiting faculty in The Ohio State University’s College of Public Health.
The research team used the dietary inflammatory index, a tool developed a decade ago that includes 45 dietary components to examine the diets of more than 34,500 adults included in the 2005–2018 National Health and Nutrition Examination Survey.
Based on self-reported diets, they used the tool to assign inflammation values ranging from −9 to 8, where 0 represents a neutral diet. About 34% of those in the study had anti-inflammatory diets, and the remaining 9% had neutral dietary inflammatory levels
Older dietary measures look at the intake of certain food groups (such as fruits, vegetables and dairy) or macronutrients (such as carbohydrates, proteins and fats) that align with national diet recommendations or certain diets like keto or paleo.
“But inflammation is an important element to consider and the overall balance of diet is most important,” Meadows said.
“Even if you’re eating enough fruits or vegetables, if you’re having too much alcohol or red meat, then your overall diet can still be pro-inflammatory.”
Meadows said she’s less interested in labeling foods as “bad” and more interested in thinking about anti-inflammatory foods as tools people can employ to boost health.
“There’s a potential here to think about positive interventions, such as adding more garlic, ginger, turmeric and green and black tea — which are all anti-inflammatory — to your diet,” she said. “Moving toward a diet with less inflammation could have a positive impact on a number of chronic conditions, including diabetes, cardiovascular disease and even depression and other mental health conditions.”
Other examples of anti-inflammatory foods are mostly unprocessed including whole grains, green leafy vegetables (such as spinach), legumes (such as beans and lentils), fatty fish (such as salmon) and berries. Challenges to eating a less inflammatory diet include poor access to fruits, vegetables and other foods that can contribute to better health — and even when those foods are available, they can sometimes be more costly, creating a barrier for those with low incomes, Meadows said.
Many people also have elevated chronic inflammation due to non-dietary factors including stress and adverse childhood experiences, she said. “There are a lot of factors that contribute to chronic inflammation, and they all interact – even sleep is a key component. Diet can be used as a tool to combat that,” Meadows said.
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 defence against pathogens—while the keto diet prompted responses associated with adaptive immunity—pathogen-specific immunity built through daily life exposure and vaccination. 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 how they could affect 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 poorly 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 fibre and low in fat.
The study was conducted by researchers from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and the 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. Blood, urine, and stool were collected for analysis throughout the study period. 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 and 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 participants’ microbiomes, causing shifts in the abundance of gut bacterial species previously 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 immune system components. 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.
Popular weight-loss diet also associated with higher levels of LDL cholesterol
The ketogenic or “keto” diet, which involves consuming very low amounts of carbohydrates and high amounts of fats, has been gaining popularity. However, a new study presented at the American College of Cardiology’s Annual Scientific Session Together With the World Congress of Cardiology suggests that a “keto-like” diet may be associated with higher blood levels of “bad” cholesterol and a twofold heightened risk of cardiovascular events such as chest pain (angina), blocked arteries requiring stenting, heart attacks and strokes.
“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,” said Iulia Iatan, MD, PhD, attending physician-scientist at the Healthy Heart Program Prevention Clinic, St. Paul’s Hospital and University of British Columbia’s Centre for Heart Lung Innovation in Vancouver, Canada, and lead author of the study. “To our knowledge, our study is one of the first to examine the association between this type of dietary pattern and cardiovascular outcomes.”
Carbohydrates are the body’s first “go-to” source for fuel to provide energy for daily life. Low-carbohydrate, high-fat (LCHF) diets, like a keto diet, restrict consumption of carbohydrates (e.g., bread, pasta, rice and other grains, baked goods, potato products such as fries and chips, and high-carbohydrate fruits and vegetables). By depriving the body of carbohydrates, it is forced to start breaking down fat for energy instead. The breakdown of fat in the liver produces ketones, chemicals that the body uses as energy in the absence of carbohydrates—hence the name ketogenic, or “ketone producing.” Proponents of a ketogenic diet generally suggest limiting carbohydrates to 10% of total daily calories, protein to 20% to 30% and obtaining 60% to 80% of daily calories from fat.
Some previous studies have shown that an LCHF diet can lead to elevated levels of LDL cholesterol in some people. While elevated LDL cholesterol is a known risk factor for heart disease (caused by atherosclerosis, a buildup of cholesterol in the coronary arteries), the effects of an LCHF diet on risk for heart disease and stroke have not been well studied, Iatan said.
For this study, Iatan and her colleagues defined an LCHF diet as consisting of no more than 25% of total daily energy or calories from carbohydrates and more than 45% of total daily calories from fat. They dubbed this an LCHF diet and “keto-like” because it is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet. They defined a “standard diet” as individuals not meeting these criteria and having more balanced eating habits.
The research team 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. Upon enrollment in the biobank, 70,684 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 their diet during the 24-hour reporting period met the study’s definition of an LCHF. These participants were matched by age and sex with 1,220 individuals who reported eating a standard diet. This resulted in 73% of the participants in each group being women and the group’s average age was 54 years. Those on an LCHF diet had an average body mass index (BMI) of 27.7; those on a standard diet, 26.7. A BMI of 25 to 30 falls within the overweight range.
Compared with participants on a standard diet, those on an LCHF diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (apoB), the protein component that sits on LDL and other atherogenic lipoprotein particles. Previous studies have shown that elevated apoB may be a better predictor than elevated LDL cholesterol for risk of cardiovascular disease, Iatan said. 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. In all, 9.8% of participants on an LCHF diet experienced a new cardiac event, compared with 4.3% of those on a standard diet, a doubling of risk for those on an LCHF diet.
“Among the participants on an LCHF diet, we found that those with the highest levels of LDL cholesterol were at the highest risk for a cardiovascular event,” Iatan said. “Our findings suggest that people who are considering going on an LCHF diet should be aware that doing so could lead to an increase in their levels of LDL cholesterol. Before starting this dietary pattern, they should consult a health care provider. While on the diet, it is recommended they have their cholesterol levels monitored and should try to address other risk factors for heart disease or stroke, such as diabetes, high blood pressure, physical inactivity and smoking.”
The study’s findings also suggest that not everyone responds to an LCHF diet in the same way.
“On average, cholesterol levels tend to rise on this diet, but some people’s cholesterol concentrations can stay the same or go down, depending on several underlying factors,” Iatan said. “There are inter-individual differences in how people respond to this dietary pattern that we don’t fully understand yet. One of our next steps will be to try to identify specific characteristics or genetic markers that can predict how someone will respond to this type of diet.”
A limitation of the study is that participants provided dietary information at only one point in time, which should be considered when interpreting the study findings, Iatan said. Moreover, self-reports of food consumption can be inaccurate, though Iatan said this questionnaire has been extensively validated.
Because the study was observational, it can only show an association between the diet and an increased risk for major cardiac events, not a causal relationship. However, Iatan said the findings merit further research in prospectively designed studies, especially when approximately 1 in 5 Americans report being on a low-carb, keto-like or full keto diet.
Keto and paleo diets were found to be the least sustainable — and have the lowest diet quality scores — of the six popular diets examined
This may be tough to swallow for those on keto or paleo diets.
A new study from Tulane University which compared popular diets on both nutritional quality and environmental impact, found that the keto and paleo diets, as eaten by American adults, scored among the lowest on overall nutrition quality and were among the highest on carbon emissions.
The keto diet, which prioritizes high fat and low carbs, was estimated to generate almost 3 kg of carbon dioxide for every 1,000 calories consumed. The paleo diet, which eschews grains and beans in favour of meats, nuts and vegetables, received the next lowest diet quality score and also had a high carbon footprint, at 2.6 kg of carbon dioxide per 1,000 calories.
The study, published in The American Journal of Clinical Nutrition, compiled diet quality scores using data from more than 16,000 adult diets collected by the CDC’s National Health and Nutrition Examination Survey. Individual diets were assigned point values based on the federal Healthy Eating Index and average scores were calculated for those eating each type of diet.
The study’s senior author Diego Rose, professor and nutrition program director at Tulane University School of Public Health and Tropical Medicine, said that while researchers have examined the nutritional impact of keto and paleo diets, this is the first study to measure the carbon footprints of each diet, as consumed by U.S. adults, and compare them to other common diets.
“We suspected the negative climate impacts because they’re meat-centric, but no one had really compared all these diets – as they are chosen by individuals, instead of prescribed by experts – to each other using a common framework,” Rose said.
On the other end of the spectrum, a vegan diet was found to be the least impactful on climate, generating 0.7 kg of carbon dioxide per 1,000 calories consumed, less than a quarter of the impact of the keto diet. The vegan diet was followed by vegetarian and pescatarian diets in increasing impact.
The pescatarian diet scored highest on nutritional quality of the diets analyzed, with vegetarian and vegan diets following behind.
The omnivore diet – the most common diet, represented by 86% of survey participants – sat squarely in the middle of the pack of both quality and sustainability. Based on the findings, if a third of those on omnivore diets began eating a vegetarian diet, on average for any given day, it would be equivalent to eliminating 340 million passenger vehicle miles.
Notably, however, when those on omnivorous diets opted for the plant-forward Mediterranean or fatty meat-limiting DASH diet versions, both carbon footprints and nutritional quality scores improved.
“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant- based diet,” Rose said. “Based on our results, that would reduce your footprint and be generally healthy. Our research also shows there’s a way to improve your health and footprint without giving up meat entirely.”
A 2021 United Nations-backed study found that 34% of greenhouse gas emissions come from the food system. The major share of those emissions come from food production, with beef being responsible for 8-10 times more emissions than chicken production and over 20 times more emissions than nut and legume production.
While the environmental impacts of specific foods have been studied extensively, Rose said this study was important because “it considers how individuals select popular diets that are composed of a wide variety of foods.”
Going forward, Rose still has questions about how to encourage eating habits that are better for people and the planet.
“I think the next question is how would different policies affect outcomes and how could those move us toward healthier, more environmentally friendly diets?” Rose said.
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