FDA Takes Action to Make a Treatment Available for Autism Symptoms

The U.S. Food and Drug Administration today initiated the approval of leucovorin calcium tablets for patients with cerebral folate deficiency (CFD), a neurological condition that affects folate (a vitamin essential for brain health) transport into the brain. Individuals with cerebral folate deficiency have been observed to have developmental delays with autistic features (e.g., challenges with social communication, sensory processing, and repetitive behaviors), seizures, and problems with movement and coordination.

The FDA has conducted a systematic analysis of literature published between 2009-2024, including published case reports with patient-level information, as well as mechanistic data, and has determined that the information supports a finding that leucovorin calcium can help individuals suffering from CFD.  

"We have witnessed a tragic four-fold increase in autism over two decades,” said FDA Commissioner Marty Makary, M.D., M.P.H. “Children are suffering and deserve access to potential treatments that have shown promise. We are using gold standard science and common sense to deliver for the American people.”   

FDA Responds to Evidence of Possible Association Between Autism and Acetaminophen Use During Pregnancy

 

The U.S. Food and Drug Administration today initiated the process for a label change for acetaminophen (Tylenol and similar products) to reflect evidence suggesting that the use of acetaminophen by pregnant women may be associated with an increased risk of neurological conditions such as autism and ADHD in children. The agency also issued a related letter alerting physicians nationwide.  

“The FDA is taking action to make parents and doctors aware of a considerable body of evidence about potential risks associated with acetaminophen,” said FDA Commissioner Marty Makary, M.D., M.P.H. “Even with this body of evidence, the choice still belongs with parents. The precautionary principle may lead many to avoid using acetaminophen during pregnancy, especially since most low-grade fevers don’t require treatment. It remains reasonable, however, for pregnant women to use acetaminophen in certain scenarios.”  

Evidence in recent years has suggested a correlation between acetaminophen use during pregnancy and subsequent diagnosis of conditions like autism and ADHD. Multiple large-scale cohort studies, including the Nurses’ Health Study II and the Boston Birth Cohort, find this association. Some studies have described that the risk may be most pronounced when acetaminophen is taken chronically throughout pregnancy.  

It is important to note that while an association between acetaminophen and neurological conditions has been described in many studies, a causal relationship has not been established and there are contrary studies in the scientific literature. It is also noted that acetaminophen is the only over-the-counter drug approved for use to treat fevers during pregnancy, and high fevers in pregnant women can pose a risk to their children. Additionally, aspirin and ibuprofen have well-documented adverse impacts on the fetus.

Vitamin D3 concentrations are lowered by a vitamin D supplement

 

Taking vitamin D2 might lower the body's levels of the more efficient form of vitamin D, vitamin D3, according to new research from the University of Surrey, John Innes Centre and Quadram Institute Bioscience. Many people take vitamin D supplements to support their bone and immune health and meet the UK government recommendation of 10 micrograms (µg) each day, especially during the winter months. 

There are two forms of vitamin D supplements available: vitamin D2 and vitamin D3. Researchers have found that taking vitamin D2 supplements can lead to a drop in the body's concentration of vitamin D3, which is the form our bodies naturally produce from sunlight and use most effectively to raise overall vitamin D levels.  

The study, published in Nutrition Reviews, analysed data from randomised controlled trials and found that vitamin D2 supplementation resulted in a reduction in vitamin D3 levels compared to those not taking a vitamin D2 supplement. In many of the studies, the vitamin D3 levels went lower than in the control group. 

Emily Brown, PhD Research Fellow and Lead Researcher of the study from the University of Surrey's Nutrition, Exercise, Chronobiology & Sleep Discipline, said: 

"Vitamin D supplements are important, especially between October and March, when our bodies cannot make vitamin D from sunlight in the UK.  However, we discovered that vitamin D2 supplements can actually decrease levels of vitamin D3 in the body, which is a previously unknown effect of taking these supplements. This study suggests that subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals over vitamin D2."  

Professor Cathie Martin, Group Leader at the John Innes Centre, said:  

“This meta-analysis highlights the importance of ensuring plant-based vitamin D3 is accessible in the UK.” 

This research supports a previous study published in Frontiers in Immunology, led by Professor Colin Smith from the University of Surrey, which suggests that vitamin D2 and D3 do not have identical roles in supporting immune function. Vitamin D3 has a modifying effect on the immune system that could fortify the body against viral and bacterial diseases.   

Professor Colin Smith said: 

“We have shown that vitamin D3, but not vitamin D2, appears to stimulate the type I interferon signalling system in the body - a key part of the immune system that provides a first line of defence against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body.” 

Further research into the different functionalities of vitamin D2 and D3 should be a priority in deciding whether vitamin D3 should be the first-line choice of vitamin D supplement, subject to individual requirements. 

Professor Martin Warren, Chief Scientific Officer at the Quadram Institute, said: 

 "Vitamin D deficiency represents a significant public health concern, especially during the winter months with significant deficiency across the UK population. This collaborative research effort aligns well with the Quadram Institute’s mission to deliver healthier lives through food innovation to enhance the nutrient density of the food we eat. Tackling this with the most effective form of vitamin D supplementation or fortification is of the utmost importance to the health of the nation." 

Consuming more legumes and less red and processed meat = positive impact on men’s health

 A University of Helsinki study found that partially replacing red and processed meat with pea- and faba bean–based foods resulted in reduced total and ‘bad’ LDL cholesterol levels in men, along with weight loss.

On average, men consume significantly more red and processed meat than is recommended, and more than women do. The high nutritional value of legumes makes them well suited to replacing meat. However, they do not naturally contain vitamin B12, which is found in animal-derived foods. The BeanMan study investigated how partially replacing red and processed meat with legumes thriving in Finnish conditions affected men’s health and levels of critical micronutrients in the blood.

In the study, 102 working-age men were divided into two groups. For six weeks, one group ate 760 grams of red and processed meat a week, that is, the average amount consumed by Finnish men. This accounted for one-quarter of total protein intake. 

Throughout the study, the other group’s diet included a substantial proportion of foods based on peas and faba beans, constituting 20% of total protein intake. In addition, the group members ate 200 grams of red and processed meat per week, comprising 5% of total protein intake. This corresponds to the recommended upper limit for red meat consumption in the planetary health diet. 

While the participants otherwise continued to follow their own diet, they consumed no red or processed meat or legumes other than the foods supplied as part of the study. Red meat encompassed beef and pork, while processed meat comprised sausages and cold cuts made from the same. 

The men who ate a large amount of pea- and faba bean–based foods alongside meat during the study lost an average of one kilo in weight, whereas those who ate only meat dropped just 300 grams.  The results indicate that eating more legumes and less red and processed meat reduces total and LDL cholesterol levels andthe risk of cardiovascular disease and type 2 diabetes, and may support weight management.

The positive change in blood cholesterol levels was expected for the legume group due to the enhanced quality of fat consumed. However, the researchers were surprised by the weight loss. 

“In a trial setting, participants often monitor their eating more closely, which may contribute to weight loss. But in this study, despite its relatively short duration, the legume group lost significantly more weight than the meat group. We didn’t encourage the participants to lose weight, but asked them to continue eating as before, apart from consuming the foods we provided,” says Professor of Molecular Nutrition Anne-Maria Pajari of the Faculty of Agriculture and Forestry.

Partially replacing meat does not jeopardise critical nutrient intake

While cutting back on red meat reduced vitamin B12 intake in the legume group, the status of this vitamin remained at a safe level by the end of the study. Moreover, dietary iron intake was higher for the legume group, whereas no difference was observed between the groups in iodine intake. 

“In the short term, critical nutrient intake wasn’t jeopardised in the legume group. This was likely because the participants remained on mixed diets, rather than cutting out any foods entirely. However, research is needed on the effects of switching to plant-based diets on the body’s nutritional status, particularly in vulnerable population groups, such as children and older adults,” states Pajari. 

She notes that the legume group participants followed their diet successfully even though it included more legumes and less red meat than typically recommended. 

“The legume food products we provided were quick to cook, making them easy to use. We also handed out recipes to encourage cooking. Based on our findings, I believe a moderate dietary change towards a more sustainable direction, using peas, beans and lentils, is possible for most of us,” she says, delighted.

The BeanMan study was conducted as part of the soon-to-conclude, multidisciplinary Leg4Life (Legumes for Sustainable Food System and Healthy Life) project, funded by the Research Council of Finland’s Strategic Research Council. The study’s previously reported findings demonstrated that eating more legumes and less red and processed meat is safe for both bone health and amino acid intake. Results on intestinal health will be published later.

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Cocoa extract supplement reduced key marker of inflammation and aging

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Could cocoa extract supplements rich in cocoa flavanols reduce inflammation and, in turn, prevent age-related chronic diseases? In a new study from the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), investigators from Mass General Brigham and their colleagues looked at changes in five age-related markers of inflammation among participants who received daily cocoa supplements over several years. They found that hsCRP—an inflammatory marker that can signal increased risk of cardiovascular disease—decreased in participants taking the cocoa extract supplement, suggesting its anti-inflammatory potential may help explain its heart-protective effects. Their results are published in Age and Ageing.

Nutritional interventions have become an increasingly attractive solution for slowing inflammatory aging, so called “inflammaging.” Cocoa extract has been shown in previous, smaller studies to reduce inflammatory biomarkers, thanks to flavanols—small, bioactive compounds found not only in the cocoa bean but also berries, grapes, tea, and other plant-based foods. To bridge the gap between these studies and humans, researchers launched the large-scale COSMOS trial, which examines the effects of cocoa extract on cardiovascular disease, and whether inflammaging may explain those effects.

“Our interest in cocoa extract and inflammaging started on the basis of cocoa-related reductions in cardiovascular disease,” said corresponding author Howard Sesso, ScD, MPH, associate director of the Division of Preventive Medicine and associate epidemiologist at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “We also appreciate the important overlap between healthy aging and cardiovascular health, where aging-related inflammation can harden arteries and lead to cardiovascular disease. Because of that, we wanted to see whether multi-year cocoa extract supplementation versus a placebo could modulate inflammaging—and the data suggests it does.”

Between 2014 and 2020, Brigham and Women’s Hospital led the COSMOS trial, a large-scale, randomized, double-blind, placebo-controlled clinical trial with 21,442 participants over 60 years old, finding that cocoa extract supplementation decreased cardiovascular disease mortality by 27%.

In this new study, researchers collected and analyzed blood samples of 598 COSMOS participants to measure several inflammaging biomarkers: three pro-inflammatory proteins (hsCRP, IL-6, and TNF-α), one anti-inflammatory protein (IL-10), and one immune-mediating protein (IFN-γ). Comparing changes in these biomarkers measured at baseline, 1, and 2 years follow-up, hsCRP levels decreased by 8.4% each year compared with placebo, while the other biomarkers remained relatively consistent or increased modestly.

“Interestingly, we also observed an increase in interferon-γ, an immune-related cytokine, which opens new questions for future research,” said senior author Yanbin Dong, MD/PhD, Director of the Georgia Prevention Institute (GPI) and cardiologist/population geneticist at the Medical College of Georgia/Augusta University. “While cocoa extract is not a replacement for a healthy lifestyle, these results are encouraging and highlight its potential role in modulatingi nflammation as we age.

The decrease in hsCRP may help explain the cardio-protective effects seen with cocoa extract supplement in the larger COSMOS trial, where participants experienced a reduction in cardiovascular disease death. Researchers said that changes in the other inflammaging markers, including a small reduction in IL-6 observed in female but not male participants, warrant additional study. The team will continue to evaluate the COSMOS trial to determine whether the cocoa - and multivitamin - regimens can curb more severe inflammaging, as well as other important aging-related health outcomes.

“This study calls for more attention to the advantage of plant-based foods for cardiovascular health, including cocoa products rich in flavanols,” added Sesso. “It reinforces the importance of a diverse, colorful, plant-based diet—especially in the context of inflammation.” 

Resistance training may improve nerve health, slow aging process

 Simple resistance training may help counteract age-related nerve deterioration that puts seniors at risk of injuries from falls and other accidents, according to cross-institutional research led by Syracuse University postdoctoral researcher JoCarol Shields and Department of Exercise Science Professor Jason DeFreitas.

The nerves that control our muscles naturally degrade and become slower as we age, a process referred to as denervation. This degradation is especially problematic in sedentary individuals. Counteracting this deterioration with exercise could help seniors enjoy greater independence and improve their quality of life.

Resistance exercise, also known as strength training, is a type of physical activity that involves working against an external force to improve muscle strength, size, and endurance

“For people in their 70s and 80s, it’s about preserving what you have,” says Shields, who is working in the Neural Health Research Laboratory at the David B. Falk College of Sport at Syracuse University. “The aging process is going to happen no matter what, but can we slow it down.”

The study was published Sept. 16 in the Medicine & Science in Sports & Exercise (MSSE), the leading multidisciplinary research journal for the American College of Sports Medicine and one of the flagship journals within the fields of sports medicine and exercise physiology.

“Shields and colleagues show that nerve function in older adults is trainable, which may also have long-term implications for nerve health, motor function, independence, and quality of life,” Editor-in-Chief Andrew Jones wrote in MSSE’s current issue. “This work could stimulate investigations into whether resistance training is an effective countermeasure for other, non-age related, sources of nerve degradation (for example, nervous system disorders).”

For their study, the researchers sought to determine the effects of resistance training on nerve conduction velocity (NCV), and if changes in NCV are dependent on age. Testing 48 subjects ranging from 18 to 84 years old, the researchers recorded NCV in the forearm and maximal strength before and after four weeks of handgrip training in both arms (training was conducted three times a week).

To measure each subject’s NCV, the researchers used nerve conduction tests that stimulated the nerves in the muscles of the forearm and measured how fast it took to activate the muscle.

In the post-training tests, every senior that performed the training showed improvement in their nerve conduction. A nerve contains both fast and slow motor neurons, and the fast neurons are the first to deteriorate, disconnect from muscle, and become inactive with age. The researchers hypothesize that the training reactivated these fast neurons in the older participants, a process called reinnervation.

“When you lose fast neurons, you also lose the fast muscle fibers that are activated by them, and then your power, or the speed at which you can produce force, decreases,” said DeFreitas, chair of the Department of Exercise Science at Falk College. “If you can reactivate those lost neurons, you can produce force faster again and that has practical implications so that a slip or a trip doesn’t become a terrible fall.”

The research team plans to conduct further studies to determine the role that exercise interventions play in mitigating age-related nerve deterioration, and if the reactivation of fast neurons translates to other parts of the body.

“If we’re reactivating those neurons that started to die, that can play a significant role in the preservation of strength and avoiding disability with aging,” DeFreitas said. “That to me is the likely hypothesis, so that’s the premise of the follow-up work we’re conducting.”

Adopting healthy habits can improve cognitive decline

 An estimated 7.2 million Americans over age 65 currently live with Alzheimer’s disease (AD). That number is expected to nearly double to 13.8 million by 2060. These increases reflect more than demographic shifts; they point to a growing public health crisis that requires a new, proactive approach. While chronological age is the strongest known risk factor for cognitive decline, losing cognitive function is not an inevitable part of aging.

As AD and other forms of cognitive decline continue to rise at an alarming rate, researchers from Florida Atlantic University’s Charles E. Schmidt College of Medicine, highlight a powerful and untapped path to prevention. 

In a commentary published in The American Journal of Medicine, the researchers urge clinicians, public health professionals and policymakers to implement coordinated efforts to support lifestyle-based interventions that can help reduce the growing burden of cognitive decline in the United States and worldwide.

“While deaths from cardiovascular disease have declined since 2000, deaths from Alzheimer’s disease have surged by more than 140%,” said Charles H. Hennekens, M.D., FACPM, FACC, co-author, the First Sir Richard Doll Professor of Medicine and Preventive Medicine, and senior academic advisor, Schmidt College of Medicine. “At the same time, it is estimated that up to 45% of dementia risk could be attributed to modifiable lifestyle and environmental factors.”

Lifestyle risk factors like physical inactivity, poor diet, obesity, alcohol use, and conditions such as hypertension, diabetes, depression, and social or intellectual isolation are believed to contribute to cognitive decline. The authors point out that the same therapeutic lifestyle changes proven effective for reducing risks of cardiovascular and other major diseases may also help reduce cognitive decline – potentially with additive effects when multiple risk factors are present.

The commentary highlights the recently published results from POINTER, the first large-scale U.S-based randomized trial to test whether intensive lifestyle changes can improve cognitive outcomes in older adults at high risk of decline. In this trial, participants who were assigned at random to a structured, team-based lifestyle intervention showed statistically significant and clinically meaningful improvements in global cognition over two years. These gains were especially notable in executive functions such as memory, attention, planning and decision-making. The intervention emphasized regular physical activity, a combination of Mediterranean and DASH-style diets, cognitive stimulation and social engagement – reinforced through ongoing professional guidance and group support.

These findings are similar to an earlier Finnish trial, the FINGER trial, in which participants with elevated cardiovascular risk scores assigned at random to a multidomain lifestyle approach experienced cognitive benefits.

“The data from both these landmark, large scale randomized trials demonstrate that lifestyle changes – previously shown to reduce heart disease and cancer – also hold transformative potential for brain health,” Hennekens said.

The researchers also speculated about biological mechanisms that may underlie these benefits. Physical activity, for example, increases brain-derived neurotrophic factor, which supports hippocampal growth, while also improving blood flow and reducing inflammation. Healthy dietary patterns like the Mediterranean and DASH diets can lower oxidative stress and improve insulin sensitivity as well as risks of cardiovascular disease.  Quitting smoking may help preserve brain structure and white matter integrity, and regular social and cognitive engagement promotes neuroplasticity and mental resilience.

“The implications for clinical practice, public health and government policy are potentially enormous,” said Parvathi Perumareddi, D.O., co-author and an associate professor of family medicine in the Schmidt College of Medicine. “Clinicians now have powerful, evidence-based tools to help their patients prevent or slow cognitive decline – tools that go beyond medications, are generally low-risk, and are cost-effective. Public health agencies could adopt the framework of trials like POINTER and FINGER to develop brain health programs.” 

On the policy front, the researchers note that potential cost savings are large, particularly when considering the high price and limited effectiveness of many new pharmacologic agents, which may cause common and less serious side effects like nausea, headache and fatigue, as well as more rare but more serious risks like confusion or gastrointestinal bleeding. Modeling studies suggest that reducing key risk factors by even 10% to 20% each decade could lower the burden of cognitive decline by up to 15%.

Beyond the health care system, the societal costs of dementia are staggering. In 2024, nearly 12 million family members and unpaid caregivers provided an estimated 19.2 billion hours of care to individuals living with dementia – amounting to a societal cost of more than $413 billion. Caregiving also takes an emotional toll, often resulting in mental health challenges and caregiver burnout. The researchers emphasize that these realities underscore the need for practical, community-based solutions that support both patients and caregivers and reduce the long-term burden on families and the economy.

“While more research is needed, the current totality of evidence supports a clear path forward: invest in lifestyle-based strategies to protect brain health,” said Hennekens. “Doing so will not only benefit individuals at risk but also serve as a powerful tool for reducing national and global health care burdens related to cognitive decline.”