A controversial subject for sure....as I am slightly reactive to eggs (both yolk and white) I tend to eat them once or twice a week and try to stay away from too many baked goods, containing eggs, therefore I cannot comment on this from personal experience...

I do, however wish to point out that research is subjective and many of the variants are not covered here, like were the people eating organic or conventional eggs....there is a difference between what free range chickens and conventional chickens eat and are fed. The linoleic acid content in conventional eggs will be way higher etc. (more inflammatory)

I always recommend eating eggs from free range chickens that have not been consuming GMO corn and I also like to know where my organic eggs are coming from.

Having said that....

You decide how this fits or feels for you.

A Beloved Food That Surprisingly Has Been Found to Contribute to Diabetes

Ronald Grisanti D.C., D.A.B.C.O., DACBN, MS, CFMP

Over the last few years I started seeing an unanticipated trend that totally took me by surprise. The trend was totally fit individuals who were eating three to six eggs a day were developing Type 2 Diabetes (T2D) confirmed with an elevated Hemoglobin A1c levels ranging from 5.8 to 6.2.!

 

Ha1c Readings from Two Very Fit Patients Eating 3-6 Eggs Per Day

The A1C test—also known as the hemoglobin A1C or HbA1c test—is a simple blood test that measures your average blood sugar levels over the past 3 months. It's one of the commonly used tests to diagnose prediabetes and diabetes, and is also the main test to help you and your health care team manage your diabetes.

My Research And Discovery on The Relationship Between Increased Egg Consumption and the Trend Toward Diabetes

According to a study published 2021 in the British Journal of Nutrition, consuming one or more eggs per day may increase the risk of diabetes by 60%!.

Researchers compared egg consumption with blood glucose levels in more than 8,000 participants from the China Health and Nutrition Survey. Those who habitually consumed the most eggs increased their risk for diabetes when compared to those who ate the fewest eggs. 

A study published in Nutrition found an increased risk for diabetes and high cholesterol among Chinese women, while research published in Circulation found a link between higher egg consumption and prevalence of diabetes mellitus and hypertension.

Although an older study, the medical journal, Circulation from a meta-analysis and data from the Physicians' Health Study and Women's Health Study showed an increased risk for diabetes of up to 77% with seven or more eggs consumed per week.

Higher egg consumption was associated with higher blood glucose in subjects with T2D.

What the Medical Literature is Leaning Toward as it Relates to Diabetes and Eggs

Many studies, including meta-analyses, systematic reviews, case-control studies, and large-scale epidemiological studies, all point in the same direction. 

Eating eggs increases your risk for the development of type 2 diabetes, heart disease, diabetes complications, and all-cause mortality. 

Whether you are currently living with diabetes, consuming an increased number of eggs per week can significantly elevate your risk for developing diabetes and its health related complications such as cardiovascular disease and kidney disease.

Dr. Grisanti's Comments:

My analysis of the research was an eye-opener and to be quite honest if it wasn't for the fact that I was seeing what appeared to be perfectly fit patients exhibiting elevated Ha1c with a possible correlation of increased egg consumption, I would have been doubtful on the conclusions of these studies.

I suggest limiting egg consumption to three eggs per week

I found the following short video from Michael Greger M.D. FACLM (author of How Not to Die and his most recent book, How Not to Age) a good summary on this important topic.

https://nutritionfacts.org/video/eggs-and-diabetes/

** As a side note, I realize that there will be egg proponents that will debate me and show me other peer reviewed studies negating the contents of my article. My response will be the fact that I see the true evidence with real patients and not simply some conflicting studies. I prefer to err on the side of being cautious and do no harm. 

This is a controversial topic with two opposing sides and I have done my due diligence and weighed out the evidence and I believe over abundance of egg consumption should be carefully curtailed as to be 100% certain you are doing no metabolic damage to yourself and your patients.

If you are staunch advocate of increased egg consumption, I simply say, do the benefits out weigh the risk.

Again what I have observed in clinical practice with real patients, the lab tests do not lie and with no evidence of other reasons for compromised glucose metabolism (diabetes), I report that eggs may indeed be the culprit.

I will continue to report on my findings as I continue to monitor my patients.

References:

https://pubmed.ncbi.nlm.nih.gov/33028452/
https://pubmed.ncbi.nlm.nih.gov/20471806/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861752/
https://europepmc.org/article/med/33028452
https://pubmed.ncbi.nlm.nih.gov/26739035/
https://pubmed.ncbi.nlm.nih.gov/19017774/
https://link.springer.com/article/10.1007/s00394-017-1566-0
//www.functionalmedicineuniversity.com/Harvard-egg-diabetes.pdf

** Always consult with a physician or healthcare practitioner with significant integrative or functional medicine training before starting any of the above recommendations.

You can find a qualified and certified functional medicine practitioner by going to: www.FunctionalMedicineDoctors.com

The information on this website is not intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice. It is intended as a sharing of knowledge and information from the research and experience of Dr. Grisanti and his functional medicine community. Dr. Grisanti encourages you to make your own health care decisions based upon your research and in partnership with a qualified health care professional. Visit www.FunctionalMedicineUniversity.com for more information on our training in functional medicine. Look for practitioners who have successfully completed the Functional Medicine University's Certification Program (CFMP) www.functionalmedicinedoctors.com. This content may be copied in full, with copyright, contact, creation and information intact, without specific permission, when used only in a not-for-profit format. If any other use is desired, permission in writing from Dr. Grisanti is required

Ozempic and suicidal thoughts?

 

EU Investigates Ozempic, Weight-Loss Drug Saxenda After Suicidal Thoughts Reported

By Ludwig Burger and Maggie Fick

July 11, 2023 

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https://www.medscape.com/s/viewarticle/994162?ecd=WNL_trdalrt_pos1_230712_etid5632802&uac=149193PV&impID=5632802#vp_2>

(Reuters) - The European Medicines Agency (EMA) is investigating Novo Nordisk's diabetes drug Ozempic and weight-loss treatment Saxenda after Iceland's health regulator flagged three cases of patients thinking about suicide or self-harm.

Shares of the Danish drugmaker fell 1% on Monday following the news.

An EMA safety committee is looking into adverse events raised by the Icelandic Medicines Agency, including two cases of suicidal thoughts in those who used Ozempic, which contains the active ingredient semaglutide, and Saxenda, the regulator said.

Another patient on Saxenda, Novo's earlier and less effective weight-loss drug that contains the active ingredient liraglutide, reported thoughts of self-injury, the agency said.

Iceland's drugs regulator did not immediately respond to requests for details.

Novo Nordisk said patient safety was top priority and it treated all reports about adverse events very seriously. Its own safety monitoring so far found no "causal association" between the self-harming thoughts and the drugs, it said in a statement.

The EMA's investigation centres on medicines that contain either semaglutide or liraglutide. Novo's obesity treatment Wegovy, for which demand has surged in the United States, contains semaglutide.

The review was announced weeks after the regulator raised a thyroid cancer safety signal, a means to monitor potentially adverse effects, on several of Novo's products containing semaglutide.

Suicidal thoughts are not listed as a side effect in the EU product information for either drug.

In the United States, however, prescribing instructions for Wegovy recommend that patients are monitored for suicidal thoughts or behaviour.

According to the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard, there have been at least 60 reports of suicidal ideation since 2018 from patients on semaglutide or their health care providers.

FAERS has received at least 70 such reports since 2010 from users of liraglutide or their health care providers.

Information in these reports has not been verified and the existence of a report is not proof of causation, the FDA says.

The FDA said it monitors safety of drugs throughout their life cycle. Wegovy's trials did not suggest increased risk of suicidal behavior, but the drug's label contains a warning for suicidal behavior and ideation because of risks associated with other weight management drugs, the regulator said.

SENSITIVE

Although Iceland's regulator has flagged only three cases, the issue of suicidal thoughts linked to weight-loss drugs is sensitive and has hobbled previous attempts by the drug industry to develop lucrative weight-loss drugs.

In clinical trials for Ozempic and Saxenda, Novo excluded people with a history of psychiatric disorders or recent suicidal behavior.

Sanofi's Acomplia, which never won U.S. approval, was withdrawn in Europe in 2008 after being linked to suicidal thoughts.

Acomplia was designed to modify parts of the nervous system that regulate appetite. New weight-loss drugs such as Wegovy regulate appetite by mimicking a gut hormone, and not directly interfering with brain chemistry.

Diet pills Contrave by Orexigen Therapeutics and Qsymia by Vivus Inc, approved in the U.S. in 2014 and 2012, respectively, carry warnings on their labels about increased risk of suicidal thoughts.

Markus Manns, senior portfolio manager at Union Investment and a Novo shareholder, said that a low incidence of suicidal thoughts might be acceptable for a drug against Type 2 diabetes but not for a weight-loss drug.

The EMA said on Monday it would consider whether the review should be extended to other medicines of the same class, known as GLP-1 receptor agonists.

The EMA's ongoing thyroid cancer investigation includes all GLP-1s.

Other drugs in the class include Eli Lilly and Co's Mounjaro. Lilly did not respond to a question from Reuters on whether the EMA had contacted them to provide data for the new investigation.

Penny Ward, a visiting professor in pharmaceutical medicine at Kings College in London and an expert on EU drug safety monitoring, said the most likely outcome of the investigation would be a change in the drug's label in the EU to carry a warning of the possible side effect of suicidal thoughts.

Another drug safety expert, who spoke on condition of anonymity, said the small size of Iceland's population might have led regulators to consider only a few adverse event cases were a significant proportion and worth investigating.

(Reporting by Ludwig Burger in Frankfurt and Maggie Fick in London; Additional reporting by Bhanvi Satija in Bengaluru, Michael Erman and Patrick Wingrove in New York, Robin Respaut in San Francisco, Louise Breusch Rasmussen in Copenhagen and Jennifer Rigby in London; Editing by Savio D'Souza, Nivedita Bhattacharjee, Sriraj Kalluvila and Barbara Lewis)

There are other alternative articles and podcasts regarding this remarkable drug...listen here:

https://drtyna.substack.com/p/episode107?utm_source=podcast-email%2Csubstack&publication_id=810381&post_id=137457686&utm_campaign=email-play-on-substack&utm_medium=email&r=2da2zn#details

Are your prenatal vitamins measuring up?

 Another interesting research article I came across in Medscape on Prenatal supplements…

"Although drugstore shelves might suggest otherwise, affordable dietary supplements that provide critical nutrients in appropriate doses for pregnant women are virtually nonexistent, researchers have found.

In a new study published this month (April 2023), in the American Journal of Clinical Nutrition, investigators observed what many physicians have long suspected: most prenatal vitamins and other supplements do not adequately make up the difference of what food-based intake of nutrients leave lacking. Despite patients believing they are getting everything they need with their product purchase, they fall short of guideline-recommended requirements. (see attached research study below)

The researchers analyzed 24-hour dietary intake data from 2450 study participants across five states from 2007 to 2019. Sauder and colleagues focused on six of the more than 20 key nutrients recommended for pregnant people, and determined the target dose for vitamin A, vitamin D, folate, calcium, iron, and omega-3 fatty acids.

The researchers tested more than 20,500 dietary supplements, of which 421 were prenatal products. Only 69 products — three prenatal — included all six nutrients. Just seven products — two prenatal — contained target doses for five nutrients. Only one product, which was not marketed as prenatal, contained target doses for all six nutrients but required seven tablets a serving and cost patients approximately $200 a month.  

More than half of pregnant people in the United States are at risk of inadequate intake of vitamin D, folate, and iron from their diet alone, and one third are at risk for insufficient intake of vitamin A and calcium.

Although more than 70% of pregnant women take dietary supplements, the products do not eliminate the risks for deficiencies. The effects of inadequate nutrition during pregnancy may include neural tube defects, alterations in cardiovascular structure, and impaired neurocognitive development.

I thought it would be interesting to see how our Everyday Essentials Pregnancy (R275P), and Prenatal (R714), formulas compared to what the researchers determined as the target dose for vitamin A, vitamin D, folate, calcium, iron, and omega-3 fatty acids:

The target daily dose for Vitamin A was ≥198 mcg retinol activity equivalents (RAE) of total vitamin A (with ≤2063 mcg preformed retinol):

• Everyday Essentials Pregnancy (per daily packet): 1,500 mcg RAE (80% as mixed carotenoids and 20% as retinyl palmitate)
• Prenatal (six capsules daily): 1,500 mcg RAE (80% as mixed carotenoids and 20% as retinyl palmitate)

The target daily dose for Vitamin D3 was 7–91 mcg:

•  Everyday Essentials Pregnancy (per daily packet):  50 mcg.
• Prenatal (six capsules daily): 50 mcg.

The target daily dose for Folic Acid was 169–720 mcg dietary folate equivalents (DFE) of folic acid:

•  Everyday Essentials Pregnancy (per daily packet): 1,700 mcg DFE (as calcium L-5-methyltetrahydrofolate)
• Prenatal (six capsules daily): 1,700 mcg DFE (as calcium L-5-methyltetrahydrofolate)

The target daily dose for Calcium was  383–943 mg. 

•  Everyday Essentials Pregnancy (per daily packet): 400 mg. (as calcium citrate)
• Prenatal (six capsules daily): 400 mg. (as calcium citrate)

The target daily dose for Iron was 13–22 mg.

•  Everyday Essentials Pregnancy (per daily packet): 30 mg. (as ferrous bisglycinate chelate) (Ferrochel™) 
• Prenatal (six capsules daily): 30 mg. (as ferrous bisglycinate chelate) (Ferrochel™) 

The target daily dose for Omega-3 Fatty Acids was ≥59 mg ω-3 FAs:

•  Everyday Essentials Pregnancy (per daily packet): Total Omega-3 Fatty Acids - 1.6 grams (1600 mg.) - (860 mg. of EPA, 580 mg. of DHA and 160 mg. of Additional Omega-3 Fatty Acids)  
• Prenatal (six capsules daily): None

NOTE: Other than the Prenatal (R714), NOT containing Omega-3 Fatty Acids, BOTH NutriDyn prenatal formulas met or exceeded the research determined target dose for vitamin A, vitamin D, folate, calcium, iron, and in the case of Everyday Essentials Pregnancy, the omega-3 fatty acids.

Also, our retail price for a month supply is $67.25 for Everyday Essentials Pregnancy (R275P), and $42.25 for the Prenatal (R714)… NOT $200.00 a month!

Original article:Dietary supplements and requirements in pregnancy 

Most pregnant women in the United States (US) are at risk of inadequate intake of key nutrients during pregnancy from foods alone. Current dietary supplement practices reduce risk of inadequacy for only some nutrients and induce excessive intake of other nutrients.

Objectives

Our study aimed to estimate the doses of supplementation needed to help most pregnant women achieve the recommended intake without exceeding upper limits for key prenatal nutrients and to identify US dietary supplements providing these doses.

Obesity and our children

 Majority of US Children Today Will Be Obese by Age 35

Over half of today's children in the United States will be obese at the age of 35 if existing trends continue, despite the fact that currently, less than 20% of them are obese, a new simulated growth trajectory model indicates.

"Right now, about 17% of children between the ages of 2 and 19 have obesity," lead author of the new research, Zachary Ward, MPH, Harvard TH Chan School of Public Health, Boston, Massachusetts, explained in an email to Medscape Medical News.

"But we project that the majority of them — 57% — will have obesity when they turn 35," he added.

In fact, only those children with a current healthy weight have less than a 50% chance of becoming obese by the age of 35 years, the researchers say in their paper, published in the November 30, 2017 issue of the New England Journal of Medicine.

And perhaps not surprisingly, early development of obesity predicted obesity in adulthood, especially for children who were severely obese.

"Our findings highlight the importance of prevention efforts for all children as they grow up and of providing early interventions for children with obesity to minimize their risk of serious illness in the future," Dr Ward noted in a statement from his institution.

Obesity Is a Trajectory That Is Difficult to Change 

In the United States, obesity has declined recently among children between the ages of 2 and 5 years and has stabilized among those between the ages of 6 and 11 years of age but continues to rise among adolescents and adults, say Dr Ward and colleagues.

And although the obesity epidemic has been well characterized at a population level, less is known about the individual-level risk of adult obesity for a given child on the basis of current weight and age, they explain.

For their estimates, the researchers pooled five nationally representative data sets involving 41,567 children and adults who had repeated measures of height and weight over time, and they developed a simulation model to predict individual growth trajectories. They then created 1000 virtual populations of 1 million children through the age of 19 years that were representative of the 2016 US population and projected their trajectories in height and weight up to the age of 35 years.

"Among obese children, we found that the probability that they will still be obese at the age of 35 years increased with age," they report — that risk being almost 75% at the age of 35 if children are obese at the age of 2 and over 88% if they are obese at the age of 19.

Excess weight gained during childhood can therefore put children on a trajectory that is difficult to change, the authors say.

And this is particularly true when it comes to those with severe obesity — a condition that currently affects 4.5 million children in the United States. This was defined as 120% or more of the 95th percentile in children or BMI 35 mg/kg² or greater in adults.

At age 2, these children have only a one in five chance of not having obesity at age 35; at age 5, that chance drops to just one in 10.

Maintaining Healthy Weight Throughout Childhood Cuts Risk of Adult Obesity 

In contrast, children who are not obese at the age of 2 have a lower risk of becoming obese by the time they reach 35, provided they maintain a healthy weight through to the age of 19.

For example, if children are not obese at the age of 2, they have a 57.8% probability of being obese at the age of 35, but if they are still at a healthy weight at the age of 19, that risk drops down to 44.4%, the researchers point out.

But despite these figures, "we also found that the majority of obese 35-year-olds were not obese as children," the authors say.

In other words, approximately half of the prevalence of obesity seen in adulthood begins in childhood, while the remainder is explained by adult-onset obesity.

"It is critically important to implement policies and programs to prevent excess weight gain, starting at an early age," stressed senior author Steven Gortmaker, PhD, also of the Harvard TH Chan School of Public Health.

The research was supported in part by grants from the JPB Foundation, the Robert Wood Johnson Foundation, the Donald and Sue Pritzker Nutrition and Fitness Initiative, and the Centers for Disease Control and Prevention, including the Nutrition and Obesity Policy Research and Evaluation Network.The authors had no relevant financial relationships.

N Engl J Med. 2017;377:2145-2153.

ORIGINAL ARTICLE

Simulation of Growth Trajectories of Childhood Obesity into Adulthood

Zachary J. Ward, M.P.H., Michael W. Long, Sc.D., Stephen C. Resch, Ph.D., Catherine M. Giles, M.P.H., Angie L. Cradock, Sc.D., and Steven L. Gortmaker, Ph.D.

N Engl J Med 2017; 377:2145-2153November 30, 2017DOI: 10.1056/NEJMoa1703860

BACKGROUND

Although the current obesity epidemic has been well documented in children and adults, less is known about long-term risks of adult obesity for a given child at his or her present age and weight. We developed a simulation model to estimate the risk of adult obesity at the age of 35 years for the current population of children in the United States.

METHODS

We pooled height and weight data from five nationally representative longitudinal studies totaling 176,720 observations from 41,567 children and adults. We simulated growth trajectories across the life course and adjusted for secular trends. We created 1000 virtual populations of 1 million children through the age of 19 years that were representative of the 2016 population of the United States and projected their trajectories in height and weight up to the age of 35 years. Severe obesity was defined as a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or higher in adults and 120% or more of the 95th percentile in children.

RESULTS

Given the current level of childhood obesity, the models predicted that a majority of today’s children (57.3%; 95% uncertainly interval [UI], 55.2 to 60.0) will be obese at the age of 35 years, and roughly half of the projected prevalence will occur during childhood. Our simulations indicated that the relative risk of adult obesity increased with age and BMI, from 1.17 (95% UI, 1.09 to 1.29) for overweight 2-year-olds to 3.10 (95% UI, 2.43 to 3.65) for 19-year-olds with severe obesity. For children with severe obesity, the chance they will no longer be obese at the age of 35 years fell from 21.0% (95% UI, 7.3 to 47.3) at the age of 2 years to 6.1% (95% UI, 2.1 to 9.9) at the age of 19 years.

CONCLUSIONS

On the basis of our simulation models, childhood obesity and overweight will continue to be a major health problem in the United States. Early development of obesity predicted obesity in adulthood, especially for children who were severely obese. (Funded by the JPB Foundation and others.)

Folic Acid Tied to a 44% Reduction in Suicide Attempts

 

Folic Acid Tied to a 44% Reduction in Suicide Attempts

Folic acid/vitamin B9, may provide a safe and effective approach for decreasing suicidal ideation, new research suggests. After adjusting for multiple factors, results from a large pharmaco-epidemiological study showed taking folic acid was associated with a 44% reduction in suicide events.

"These results are really putting folic acid squarely on the map as a potential for large-scale, population-level prevention," lead author Robert D. Gibbons, PhD, professor of biostatistics, Center for Health Statistics, University of Chicago, Illinois, told Medscape Medical News.

"Folic acid is safe, inexpensive, and generally available, and if future randomized controlled trials show this association is beyond a shadow of a doubt causal, we have a new tool in the arsenal," Gibbons said.

Having such a tool would be extremely important given that suicide is such a significant public health crisis worldwide, he added.

The findings were published online September 28, 2022 in JAMA Psychiatry.

Previous Research "Fairly Thin"

Folate, the naturally occurring form of B9, is essential for neurogenesis, nucleotide synthesis, and methylation of homocysteine. Past research has suggested that taking folate can prevent neural tube and heart defects in the fetus during pregnancy — and may prevent strokes and reduce age-related hearing loss in adults.

In psychiatry, the role of folate has been recognized for more than a decade. It may enhance the effects of antidepressants; and folate deficiency can predict poorer response to selective serotonin reuptake inhibitors (SSRIs).

This has led to recommendations for folate augmentation in patients with low or normal levels at the start of depression treatment.

Although previous research has shown a link between folic acid and suicidality, the findings have been "fairly thin," with studies being "generally small, and many are case series," Gibbons said.

The current study follows an earlier analysis that used a novel statistical methodology for generating drug safety signals that was developed by Gibbons and colleagues. That study compared rates of suicide attempts before and after initiation of 922 drugs with at least 3000 prescriptions.

Its results showed 10 drugs were associated with increased risk of suicide attempts after exposure, with the strongest associations for alprazolam, butalbital, hydrocodone, and combination codeine/promethazine. In addition, 44 drugs were associated with decreased risk, many of which were antidepressants and antipsychotics.

"One of the most interesting findings in terms of the decreased risk was for folic acid," said Gibbons.

He and his colleagues initially thought this was because of women taking folic acid during pregnancy. But when restricting the analysis to men, they found the same effect. Their next step was to carry out the current large-scale pharmaco-epidemiological study.

Prescriptions for Pain

Researchers used a health claims database that included 164 million enrollees. The study cohort was comprised of 866,586 adults with private health insurance (81.3% women; 10.4% aged 60 years and older) who filled a folic acid prescription between 2012 and 2017.

More than half of the folic acid prescriptions were associated with pain disorders. About 48% were for a single agent at a dosage of 1 mg/d, which is the upper tolerable limit for adults — including in pregnancy and lactation.

Other single-agent daily dosages ranging from 0.4 mg to 5 mg accounted for 0.11% of prescriptions. The remainder were multivitamins.

The participants were followed for 24 months. The within-person analysis compared suicide attempts or self-harm events resulting in an outpatient visit or inpatient admission during periods of folic acid treatment vs during periods without treatment.

During the study period, the overall suicidal event rate was 133 per 100,000 population, which is one fourth the national rate reported by the National Institutes of Health of 600 per 100,000.

After adjusting for age, sex, diagnoses related to suicidal behavior and folic acid deficiency, history of folate-reducing medications, and history of suicidal events, the estimated hazard ratio (HR) for suicide events when taking folic acid was 0.56 (95% CI, 0.48 to 0.65) — which indicates a 44% reduction in suicide events.

"This is a very large decrease and is extremely significant and exciting," Gibbons said.

He noted the decrease in suicidal events may have been even greater considering the study captured only prescription folic acid, and participants may also have also taken over-the-counter products.

"The 44% reduction in suicide attempts may actually be an underestimate," said Gibbons.

Age and sex did not moderate the association between folic acid and suicide attempts, and a similar association was found in women of childbearing age.

Provocative Results?

The investigators also assessed a negative control group of 236,610 individuals using cyanocobalamin during the study period. Cyanocobalamin is a form of vitamin B12 that is essential for metabolism, blood cell synthesis, and the nervous system. It does not contain folic acid and is commonly used to treat anemia.

Results showed no association between cyanocobalamin and suicidal events in the adjusted analysis (HR, 1.01; 95% CI, 0.80 - 1.27) or unadjusted analysis (HR, 1.02; 95% CI, 0.80 - 1.28).

Gibbons noted this result boosts the argument that the association between folic acid and reduced suicidal attempts "isn't just about health-seeking behavior like taking vitamin supplements.”

Another sensitivity analysis showed every additional month of treatment was associated with a 5% reduction in the suicidal event rate.

"This means the longer you take folic acid, the greater the benefit, which is what you would expect to see if there was a real association between a treatment and an outcome," said Gibbons.

The new results "are so provocative that they really mandate the need for a well-controlled randomized controlled trial of folic acid and suicide events," possibly in a high-risk population such as veterans, he noted.

Such a study could use longitudinal assessments of suicidal events, such as the validated Computerized Adaptive Test Suicide Scale (CAT-SS), he added. This continuous scale of suicidality ranges from sub-clinical, signifying helplessness, hopelessness, and loss of pleasure, to suicide attempts and completion.

As for study limitations, the investigators note that this study was observational, so there could be selection effects. And using claims data likely underrepresented the number of suicidal events because of incomplete reporting. As the researchers point out, the rate of suicidal events in this study was much lower than the national rate.

Other limitations cited were that the association between folic acid and suicidal events may be explained by healthy user bias; and although the investigators conducted a sensitivity analysis in women of childbearing age, they did not have data on women actively planning for a pregnancy.

"Impressive, Encouraging"

Commenting for Medscape Medical News, Shirley Yen, PhD, associate professor of psychology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, described the new findings as "quite impressive" and "extremely encouraging.”

However, she noted "it's too premature" to suggest widespread use of folic acid in patients with depressive symptoms. Yen, who has researched suicide risks previously, was not involved with the current study.

She did agree with the investigators that the results call for "more robustly controlled studies. These could include double-blind randomized controlled trials that could "more formally assess" all folic acid usage as opposed to prescriptions only, Yen said.

The study was funded by the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Center of Excellence for Suicide Prevention (US Department of Veterans Affairs). Gibbons reported serving as an expert witness in cases for the US Department of Justice; receiving expert witness fees from Merck, GlaxoSmithKline, Pfizer, and Wyeth; and having founded Adaptive Testing Technologies, which distributes the Computerized Adaptive Test Suicide Scale. Yen has reported no relevant financial relationships.

Reference: JAMA Psychiatry. Published online September 28, 2022. doi:10.1001/jamapsychiatry.2022.2990. Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults <https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2796907?guestAccessKey=9b279b0a-926b-4561-8b55-e943fd904f8e&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamapsychiatry&utm_content=olf&utm_term=092822>