Glucose Intolerance

Peer-reviewed clinical pilot trial reports dramatic improvements in psychiatric and metabolic outcomes in bipolar disorder and schizophrenia SAN MATEO, Calif., April 1, 2024 /PRNewswire/ -- The field of psychiatry may have a new ally in the form of a medical ketogenic diet, according to the findings of a pioneering pilot study published in Psychiatry Research and announced today by Stanford Medicine. The study, supported by funding from Baszucki Group and others, is the first U.S.-based clinical trial to examine the therapeutic impact of a ketogenic dietary intervention for serious mental illness since 1965. Continue Reading Can a keto diet treat mental illness? | 90 Seconds w/ Lisa Kim (courtesy of Stanford Medicine) Led by Stanford University School of Medicine's Shebani Sethi, MD, ABOM, Founding Director of the Stanford Metabolic Psychiatry Clinic and Clinical Associate Professor of Psychiatry, the study represents a significant step forward in exploring the connection between metabolism and psychiatry, and in driving toward new treatment approaches in the growing epidemic of mental illness worldwide. The study trialed a 4-month intervention of a low carbohydrate ketogenic diet with individuals diagnosed with bipolar disorder or schizophrenia who also were either overweight or met criteria for metabolic abnormalities such as insulin resistance or impaired glucose tolerance. The results offer compelling evidence of the potential benefits of ketogenic dietary therapy in this population. The dual improvements in both metabolic function and psychiatric symptoms are rare in mental healthcare, where treatments often lead to significant comorbidities, including weight gain, obesity, dyslipidemia, and cardiometabolic disease. Key findings of the single-arm pilot trial include: 79% of participants showed clinically meaningful psychiatric improvement – 1 point change or more on the Clinical Global Impression scale (CGI). 75% of participants were in recovery or a recovered state at the study's conclusion (on a Clinical Mood Monitoring Scale (CMM)). 100% of participants who met the criteria for metabolic syndrome were in remission by the end of the study. 100% of fully adherent participants achieved a recovered state at the study's conclusion, demonstrating a correlation between the frequency of achieving nutritional ketosis and the level of symptom improvement. Reductions were seen in weight, body mass index (BMI), waist circumference, and visceral adipose tissue. Improvements were seen in insulin sensitivity, quality of life, and sleep. Improvements were identified across all psychiatric measures. A ketogenic nutritional intervention was safe and feasible with a high adherence rate. Dr. Sethi shared: "These results are encouraging and suggest that a ketogenic diet intervention could serve as a valuable adjunctive treatment for individuals living with serious mental illness. The dual metabolic and psychiatric improvements observed in our study represent novel findings in psychiatry, warranting further investigation." Participants in the trial expressed enthusiasm about the 4-month intervention, as reported in the published paper: "My opportunity to participate in the metabolic psychiatry study transformed my life. I gained knowledge, became able-bodied again and my mood disorder and eating disorder symptoms lessened dramatically." "It can honestly save a lot of lives. It saved mine. I would not be here today if it wasn't for keto." "I can tell you that I have never felt better than I have since using ketosis." "After we witnessed ketogenic therapy send our son's 'treatment resistant' bipolar disorder into complete and lasting remission, we immediately started funding metabolic psychiatry studies like Dr. Sethi's," said Jan Ellison Baszucki, co-founder and President of Baszucki Group. "This pilot study, the first of its kind, offers hope to those living with bipolar illness, and has successfully paved the way for larger trials that could establish ketogenic therapy as a safe and effective adjunctive or even first-line treatment for bipolar disorder and other serious mental illnesses." Based on the results of Dr. Sethi's study, along with preliminary data from a University of Edinburgh trial, Baszucki Group has followed its pilot trial grants with the establishment of a new global funding program: ReThink Bipolar: Researching Therapeutic Integration of Nutritional Ketosis in Bipolar Disorder. To date, the program has announced $8M in funding to McLean Hospital and the University of Pittsburgh for randomized controlled trials combining mechanistic explorations with a clinical ketogenic intervention. In addition, Baszucki Group's initiative, MetabolicMind.org, amplifies research and personal stories and provides free resources for patients, families and clinicians adopting metabolic therapies to improve mental health. About Baszucki Group Launched in 2021 by Roblox founder and Chief Executive Officer David Baszucki and best-selling author Jan Ellison Baszucki, Baszucki Group leverages private giving, impact investing, advocacy, storytelling and community building to drive foundational change. A primary objective of Baszucki Group is to transform mental health outcomes, beginning with bipolar disorder, by supporting initiatives at the intersection of metabolism, psychiatry, and neuroscience. To learn more about metabolic approaches to mental disorders, including ketogenic therapy, visit Metabolic Mind, a nonprofit initiative of Baszucki Group. SOURCE Baszucki Group

A small clinical trial found that the metabolic effects of a ketogenic diet may help stabilize the brain. For people living with serious mental illness like schizophrenia or bipolar disorder, standard treatment with antipsychotic medications can be a double-edged sword. While these drugs help regulate brain chemistry, they often cause metabolic side effects such as insulin resistance and obesity, which are distressing enough that many patients stop taking the medications. Now, a pilot study led by Stanford Medicine researchers has found that a ketogenic diet not only restores metabolic health in these patients as they continue their medications, but it further improves their psychiatric conditions. The results, published March 27 in Psychiatry Research, suggest that a dietary intervention can be a powerful aid in treating mental illness. "It's very promising and very encouraging that you can take back control of your illness in some way, aside from the usual standard of care," said Shebani Sethi, MD, associate professor of psychiatry and behavioral sciences and the first author of the new paper. The senior author of the paper is Laura Saslow, PhD, associate professor of health behavior and biological sciences at the University of Michigan. Making the connection Sethi, who is board certified in obesity and psychiatry, remembers when she first noticed the connection. As a medical student working in an obesity clinic, she saw a patient with treatment-resistant schizophrenia whose auditory hallucinations quieted on a ketogenic diet. That prompted her to dig into the medical literature. There were only a few, decades-old case reports on using the ketogenic diet to treat schizophrenia, but there was a long track record of success in using ketogenic diets to treat epileptic seizures. "The ketogenic diet has been proven to be effective for treatment-resistant epileptic seizures by reducing the excitability of neurons in the brain," Sethi said. "We thought it would be worth exploring this treatment in psychiatric conditions." A few years later, Sethi coined the term metabolic psychiatry, a new field that approaches mental health from an energy conversion perspective. Meat and vegetables In the four-month pilot trial, Sethi's team followed 21 adult participants who were diagnosed with schizophrenia or bipolar disorder, taking antipsychotic medications, and had a metabolic abnormality -- such as weight gain, insulin resistance, hypertriglyceridemia, dyslipidemia or impaired glucose tolerance. The participants were instructed to follow a ketogenic diet, with approximately 10% of the calories from carbohydrates, 30% from protein and 60% from fat. They were not told to count calories. "The focus of eating is on whole non-processed foods including protein and non-starchy vegetables, and not restricting fats," said Sethi, who shared keto-friendly meal ideas with the participants. They were also given keto cookbooks and access to a health coach. The research team tracked how well the participants followed the diet through weekly measures of blood ketone levels. (Ketones are acids produced when the body breaks down fat -- instead of glucose -- for energy.) By the end of the trial, 14 patients had been fully adherent, six were semi-adherent and only one was non-adherent. Feeling better The participants underwent a variety of psychiatric and metabolic assessments throughout the trial. Before the trial, 29% of the participants met the criteria for metabolic syndrome, defined as having at least three of five conditions: abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure and elevated fasting glucose levels. After four months on a ketogenic diet, none of the participants had metabolic syndrome. On average, the participants lost 10% of their body weight; reduced their waist circumference by 11% percent; and had lower blood pressure, body mass index, triglycerides, blood sugar levels and insulin resistance. "We're seeing huge changes," Sethi said. "Even if you're on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, the insulin resistance. I think that's very encouraging for patients." The psychiatric benefits were also striking. On average, the participants improved 31% on a psychiatrist rating of mental illness known as the clinical global impressions scale, with three-quarters of the group showing clinically meaningful improvement. Overall, the participants also reported better sleep and greater life satisfaction. "The participants reported improvements in their energy, sleep, mood and quality of life," Sethi said. "They feel healthier and more hopeful." The researchers were impressed that most of the participants stuck with the diet. "We saw more benefit with the adherent group compared with the semi-adherent group, indicating a potential dose-response relationship," Sethi said. Alternative fuel for the brain There is increasing evidence that psychiatric diseases such as schizophrenia and bipolar disorder stem from metabolic deficits in the brain, which affect the excitability of neurons, Sethi said. The researchers hypothesize that just as a ketogenic diet improves the rest of the body's metabolism, it also improves the brain's metabolism. "Anything that improves metabolic health in general is probably going to improve brain health anyway," Sethi said. "But the ketogenic diet can provide ketones as an alternative fuel to glucose for a brain with energy dysfunction." Likely there are multiple mechanisms at work, she added, and the main purpose of the small pilot trial is to help researchers detect signals that will guide the design of larger, more robust studies. As a physician, Sethi cares for many patients with both serious mental illness and obesity or metabolic syndrome, but few studies have focused on this undertreated population. She is founder and director of the metabolic psychiatry clinic at Stanford Medicine. "Many of my patients suffer from both illnesses, so my desire was to see if metabolic interventions could help them," she said. "They are seeking more help. They are looking to just feel better." Researchers from the University of Michigan; the University of California, San Francisco; and Duke University contributed to the study. The study was supported by Baszucki Group Research Fund, Keun Lau Fund and the Obesity Treatment Foundation.

Researchers have found that parents with chemical intolerance are more likely to report children with autism and ADHD. Autism and attention deficit hyperactivity disorder (ADHD) may be preventable if parents avoid toxic exposures and adopt interventions such as environmental house calls, according to a published study led by researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio). Using a validated, self-administered questionnaire now used worldwide to identify individuals with chemical intolerance -- the Quick Environmental Exposure and Sensitivity Inventory (QEESI©) -- parents and practitioners can determine the risk for each family and learn which exposures to avoid in their own homes where most people spend most of their day, the researchers said. A population-based survey of nearly 8,000 U.S. adults, using QEESI, found that parents with chemical intolerance scores in the top tenth percentile were 5.7 times as likely to report a child with autism and 2.1 times as likely with ADHD compared with parents in the bottom tenth percentile. The findings build on a 2015 study by UT Health San Antonio that first linked chemical intolerance in patients with the risk of their children developing autism and ADHD. "This is the first-ever article in the medical literature showing that chemical intolerance in parents can predict the risk of autism and ADHD in their children, and suggests that reducing exposures prior to and during pregnancy could help prevention," said Claudia S. Miller, MD, MS, professor emeritus with the Department of Family and Community Medicine at UT Health San Antonio. "Up to now, most interventions have been behavioral or medical, after a child is diagnosed." Miller is senior author of the study, titled, "Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children," published March 1 in the Journal of Xenobiotics, a leading toxicology publication, for its special issue on autism. Co-authors include Raymond F. Palmer, PhD, and Rodolfo Rincon, MD and specialist, both with the Department of Family and Community Medicine at UT Health San Antonio; and David Kattari, a statistician with the Marilyn Brachman Hoffman Foundation in Fort Worth, Texas. The researchers note that the study is observational, and further research is needed using controlled trials to confirm causality and further explore the proposed mechanism behind chemical intolerance. Still, they wrote, "The implications of this study, if confirmed, could be significant for preventive measures and early intervention strategies in families with parental chemical intolerance. We recommend that all prospective parents be assessed for chemical intolerance at an early age." Mast cells and autism Physician-researcher Miller in 1996 first proposed a two-stage disease process of initiation by exposure and then triggering of symptoms called TILT, for Toxicant-Induced Loss of Tolerance, as the mechanism behind chemical intolerance. She has served as a physician/environmental consultant on exposures. And her published papers have explored the impact of pesticides, the Gulf War, breast and other implants, 9/11, toxic molds, combustion products from fires, and indoor air pollutants in so-called "sick" homes, schools and workplaces, including the EPA's own headquarters building in Washington, D.C. The new study comes amid a backdrop of a 317% increase in the prevalence of autism since 2000, now occurring in one of every 36 children in the country, the researchers note, citing data originating from the Centers for Disease Control and Prevention. And the prevalence of ADHD has risen to one in eight children, also according to the CDC. Miller and colleagues in 2021 discovered a strong association between chemical intolerance and "mast cells," considered the immune system's first responders that originate in the bone marrow and migrate to the interface between tissues and the external environment where they then reside. When exposed to "xenobiotics," foreign substances like chemicals and viruses, they can release thousands of inflammatory molecules called mediators. This response results in allergic-like reactions, some very severe. These cells can be sensitized by a single acute exposure to xenobiotics, or by repeated lower-level exposures. Thereafter, even low levels of those and other unrelated substances can cause the mast cells to release the mediators that can lead to inflammation and illness. In their latest study, the researchers determined that the high chemical intolerance scores among parents of children with autism, coupled with the 2021 finding of mast-cell activation as a plausible biomechanism for chemical intolerance, suggest that: The researchers conclude that once mast cells are sensitized, diverse xenobiotics that never bothered the person previously and do not bother most people trigger multisystem symptoms that wax and wane over time. And they believe that persistent activation and triggering of mast cells may underlie the brain inflammation in autism. "The potential role of environmental toxicants in influencing epigenetics and mast cell function is a complex and emerging area of research," they wrote. "Acknowledging the need for further evidence, we hope this study contributes to an improved understanding of the potential role of environmental factors in the global rise of autism and ADHD." The authors created tools for patients, practitioners and researchers, described in their "TILT Tutorial on Chemical Intolerance, Autism, and ADHD," available along with other resources at: