Folinic Acid and Autism

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The other news related to autism was talk about the potential benefits of a pharmacological form of folate called folinic acid, an active form of vitamin B9; it’s being described as a cure for autism. In fact, the new CDC administration is fast-tracking a change in label use for the drug so it can be prescribed more often. Here’s why I think that would be a mistake.

While doing background research on an updated webinar on pregnancy, I found a paper that discussed the potential impact of mutations of the methylenetetrahydrofolate reductase (MTHFR) gene of the mother on the development of the baby. If the mother had both mutated genes, her body wouldn’t process folate very well, resulting in the over production of homocysteine as well as other issues. That could be related to the development of neurological disorders in their babies, including autism spectral disorders and ADHD.

Folinic acid is a pharmacological form of folate that has been prescribed for use with chemotherapy patients. Some forms of chemo block the MTHFR gene, and folinic acid helps ameliorate the problems related to the chemotherapy. It seemed obvious to me that it could potentially help pregnant women with the mutated MTHFR genes and thus maybe prevent the neurological disorders in the baby. That’s where it ended because there’s not enough research to suggest it will work. The research has to happen now. Simply changing the uses for the drug based on small studies and testimonials isn’t good enough without research to support it.

As far as a treatment for autism, the same holds true. We don’t know whether the impact is dependent on, or independent of, the MTHFR mutation. Perhaps in people without the gene mutation it wouldn’t be effective, or worse, detrimental in some way that is not apparent right now.

I hope reason rules the day, as exciting as the potential seem to be, but treatments should not be based on a few case studies or worse, solely on potential. We need at least some conventional proof.

Next week, I’ll turn to a couple of cooking topics to lighten things up a little.

What are you prepared to do today?

        Dr. Chet

Acetaminophen and Pregnancy

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There have been statements circulating in the health news related to autism in the past couple of weeks, and I want to provide some perspective on both. Today it’s about a link between autism and acetaminophen, the generic name for Tylenol, also known in other countries as paracetamol. Acetaminophen is also an ingredient in OTC meds such as Nyquil, Alka-Seltzer Plus, Theraflu, Goody’s Powder, Pamprin, and so on.

The controversy surrounds a recently published study that concluded pregnant women should use acetaminophen with caution under the supervision of a physician for short periods of time—which is exactly what the major medical associations already recommend.

The researchers used a statistical technique called navigation guide analysis. Essentially, it’s a meta-analysis typically used to assess environmental toxins; whether it should be used in a pharmacological analysis is not clear. In addition, there’s always the risk of bias when selecting studies for inclusion in any meta-analysis, and this is no different.

It’s especially difficult to ignore bias when three of the four researchers have provided expert evidence for plaintiffs in prior lawsuits against acetaminophen manufacturers. Even if that were not a concern, the methodology for assessing acetaminophen use depended on recall questionnaires from the mothers-to-be or their healthcare providers—not medical records. We know how well that works in Food Frequency Questionnaires, so let’s go: Did you take any pain meds in the last year? Which ones? Don’t remember? I’m not surprised—neither would I expect a woman who’s busy growing another person to remember every OTC med she took.

One more thing? Acetaminophen has been recommended for pain since the 1950s. If it were directly linked to the risk of autism or other neurological issues, it would have become apparent before this, some 75 years later. It doesn’t mean research shouldn’t continue, but for now, acetaminophen appears to be safe when taken as recommended for short periods of time under the direction of a physician. Pregnancy comes with a host of worries—which diapers, which car seat, which baby vitamins—but I’d take acetaminophen off that list.

On Saturday: is there a new treatment for autism?

What are you prepared to do today?

        Dr. Chet

Reference: Environmental Health (2025) 24:56

BMI: Still Relevant

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The study I reviewed on Tuesday was trying to establish that body fat as assessed by BIA was a better predictor of the 25-year death rate than BMI. Researchers made their case by using data collected in the 1999–2000 NHANES wave to establish that a measure of body fat that can be collected with a device such asse a scale or wrist monitor was better than hard data like height and weight as used in calculating BMI.

BIA and Body Fat

I have a unique perspective on BIA because I was part of a laboratory that collected validation data on the original devices. The researchers continuously stated that BIA was a direct measurement of body fat, but that’s not correct. BIA measures the body’s resistance to a low electrical current through the body; then that number is put into an equation combined with other measures—primarily height and weight—to calculate a percentage of body fat. In that wave of the NHANES study, they also collected waist circumference and skin-fold measures to obtain the best predictive equation for use in future studies.

I’m certain that the equations have been updated over the years, but at that time, the model for calculation of body fat was 95% dependent on height and weight. Recent standard errors of the measurement of BIA for body fat range from 3.6% to 6%. There are many reasons for errors of that size, but impedance is particularly sensitive to changes in hydration and alcohol consumption. And to be clear, BIA is not a direct measurement of body fat—it’s just simple to use.

BMI Is Still Relevant

BMI is measure of surface area. It would be nice if more surface area indicated increased muscularity, but for 99.5% of us it’s not. It’s an indication, not a direct measurement, of our body fatness. It does tell us whether we are at a normal weight for our height.

BMI should not be used with hard edges. I would be hard pressed to say that there is a significant risk of anything for someone who has a BMI of 25.9 versus a BMI of 24.9; the former indicates overweight while the latter indicates normal weight. That’s a difference of just six pounds, and a good bowel movement could account for half of that. It’s not relevant in the real world. But a BMI of over 30 indicates that someone is obese, and that affects an increasing number of people in the U.S. and other industrialized nations.

The Bottom Line

BMI is still the best metric we have for assessing whether someone is at a healthy weight for their height. We can try to account for bone size and muscularity, but that doesn’t apply to most people. Getting to a healthy weight and staying there is still the best way to live the longest and the healthiest life. There’s no splitting hairs over that.

Here’s a factoid for you: our email platform tells us how many clicks we get on whatever we send you, and by far the most-clicked page is the BMI chart in the Health Info section. And we include adjustments for frame size, so you’ll know for sure if you’re really big boned. We hope having that info easily available helps you make good decisions about your health, because a BMI chart is still the easiest way to determine whether your weight needs to come down.

What are you prepared to do today?

        Dr. Chet

Reference: Ann Fam Med 2025;23:Online. https://doi.org/10.1370/afm.240330

Are We Done with BMI?

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Body mass index has been used for decades as a way to assess whether someone is at a healthy body weight for their height. For just about as long, it’s been under attack for the people who feel it was not representative of their body composition; high muscle mass and bigger bones were two of the complaints. I’m not going to disagree, within reason, but as a way of assessing a population in large studies, it can give us some indication of how body mass is related to health.

A recently published study has called into question the use of BMI as a predictor of mortality. Researchers used the data from the 1999–2000 National Health and Nutrition Examination Survey (NHANES) to compare BMI with a method of measuring body fat called bioelectrical impendence analysis (BIA). The subjects had all metrics measured when that wave began and were 20–49. Then they obtained death certificates for everyone in the study who died in the 25 years since.

The results presented in hazard ratios demonstrated that BIA and waist circumference were significantly related to all-cause and CVD mortality while BMI was not significantly related to either. In the discussion, the researchers suggested that BIA for determining body fat percent be used in clinical settings to assess patients at risk for increased risk of dying. Is that a good idea? Should we throw out BMI? I’ll let you know on Saturday.

What are you prepared to do today?

        Dr. Chet

Reference: Ann Fam Med 2025;23:Online. https://doi.org/10.1370/afm.240330

Forever Chemicals: Maybe Not Forever

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The issue with forever chemicals, particularly PFAS, is that we can’t avoid exposure, especially because they are found in the water supply. That’s why a couple of recent studies provide some hope that a solution can be found in the foods we eat, specifically fiber.

Study One: Oat Fiber, Cholesterol, and PFAS

Canadian researchers examined the blood of 72 men who participated in a study of the use of oat fiber (beta-glucan) to lower cholesterol. They re-examined the blood samples taken for that study for PFAS levels collected before and after taking the fiber supplement for four weeks. They found that those taking the fiber showed reduced levels of some forms of PFAS in their blood.

That’s a very short study, and while done with a different purpose in mind, it still provided some direction for future research. The types of fiber and the forms of the PFAS that can be affected still need to be determined, but as I said, it provides direction.

Study Two: Inulin, PFAS, and Your Liver

Researchers began with several questions for this study in mice. First, was the damage caused by PFAS passed from mother to pups? Second, could adding a form of fiber called inulin to the diet of the pups reduce the damage from the PFAS exposure?

The answer to the first question was yes. Both liver damage and damage to the microbiome of the mice and their offspring were confirmed. Second, did the use of inulin fiber reduce and reverse the damage to both the liver and the microbiome? The answer again was yes.

This was a rodent study and humans are not rodents. However, it’s apparent that fiber supplementation was beneficial in reversing at least some of the damage caused by PFAS. Combining this with the earlier study, this is a direction that should be pursued by further research.

The Bottom Line

These two studies illustrate the benefit of basic research. It’s a beginning stage; we don’t yet know the complete mechanism of action of the fiber in relation to the microbiome and how that works with eliminating PFAS from our body, or even whether other types of fiber would work as well. As time goes on, if the research can go on, we’ll know more.

To me, we already have the direction in the recommendation of getting 25–35 grams of fiber every day. Fruit, vegetables, beans, nuts, and grains will provide us with the fiber we need every day, and a fiber supplement will give you extra insurance for those days you don’t eat as you should. If we start doing it now, we can wait for the research to catch up to our healthy lifestyle.

What are you prepared to do today?

        Dr. Chet

References:
1. https://doi.org/10.1186/s12940-025-01165-8
2. https://doi.org/10.1016/j.envpol.2025.126749

Should You Worry About Forever Chemicals?

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Per- and polyfluoroalkyl substances (PFAS for short) are found in water to the extent that 100% of the population has measurable PFAS in their blood. PFAS are synthetic chemicals that are used in many products such as fire and heat retardants and oil- and stain-resistant products. Teflon coating in cookware is the best example of the use of PFAS and why getting rid of that cookware is a good idea. Because they are chemically stable, they are called forever chemicals.

The problem is that there are known health issues associated with exposure to PFAS. Among them are a reduction in immune response and increased risk of infections of the liver and kidney damage, increased risk of cholesterol and high blood pressure, as well as issues related to reproductive health. There may be more specific issues with other organs and organ systems. Research will continue.

The question is this: if they are forever chemicals, will they stay in the body forever? There is no known detoxification system that directly eliminates PFAS from the liver, but there may be hope based on a few recent studies. We’ll take a look at those on Saturday.

In tomorrow’s Insider Conference Call, I’ll discuss a variety of topics related to vaccinations as well as whether the COVID infection impacts the health of arteries. If you become an Insider by 8 p.m. tomorrow, you can participate and get your questions answered.

What are you prepared to do today?

        Dr. Chet

Reference: https://bit.ly/3VhB612

Artificial Sweeteners—Still Your Choice

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The use of artificial sweeteners is always a contentious topic in the health field. Some people hate them, other people love them. I use them occasionally, but when it comes to benefits versus harms, I stick to the research. In this case, it’s what wasn’t stated in the headlines about the study that is important, but we can make a decision based only on what we read. This was an abstract of a presentation at a conference, so some details may have been left out that were included in the study.

The Rest of the Story

The authors established an increased risk of diabetes with artificially sweetened drinks and saccharin in any form, but there were no statistically significant diabetes symptoms linked with total intake of artificial sweeteners, sucralose, or aspartame in all foods. That means that artificial sweeteners used in other foods didn’t raise the risk of diabetes, such as added to coffee, used in ice cream or other dairy products, or used in baking. You have to wonder why it had no apparent impact.

It may be that the specific food delivery system has some impact on why it does or does not have an effect. One possibility is that if the sweetener reaches the gut bacteria, it’s modified in some way so that it doesn’t impact blood sugar or blood sugar release.

It seems odd that they used markers of diabetes as their criteria rather than physician diagnosis. They looked for fasting glucose of 126 mg/dl or more; oral glucose tolerance test 2-hour glucose of 200 mg/dl or more; hemoglobin A1C of 6.5% or more; or use of diabetes medications. The last one makes sense, because you don’t get the meds unless you have a diagnosis, but still, odd language.

FFQ—Again!

Even though the food frequency questionnaire is still a good assessment tool when used with interviews, I checked the validation studies. The correlations with food diaries and interviews for the food frequency questionnaire developed specifically for the CARDIA study were no better than 0.5, indicating a moderate positive relationship—maybe it did, maybe it didn’t. That’s much worse than other correlations used in large studies. Also, the first two nutritional assessments couldn’t have assessed sucralose because it wasn’t available until after they took place; I don’t know why sucralose was included when it wasn’t available for almost half the follow-up period.

The Bottom Line

The debate on artificial sweeteners will go on, because people love them or hate them. Based on the results of this observational study, nothing of worth has really been added to the knowledge base. The researchers called for more research to examine how artificial sweeteners impact glucose metabolism. We don’t know that it does from anything done in this study, but that doesn’t mean well-designed studies shouldn’t be done in the future. Until then, it’s up to you whether to use artificially sweetened drinks or not. Maybe a better idea is to give up the mega-burger and fries instead.

What are you prepared to do today?

        Dr. Chet

Reference:  Cur Devel in Nutr  https://doi.org/10.1016/j.cdnut.2025.107034

Artificial Sweeteners—Again

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“I’ll have the jumbo mega-burger with extra cheese, a large order of fries, and a diet cola.” Have you ever heard that when you’re standing in line? Have you maybe ordered that yourself? That’s what I thought of when I read the health headlines about the dangers of artificial sweeteners contributing to the development of diabetes.

The Coronary Artery Risk Development in Young Adults (CARDIA) study began in the early 1980s by recruiting and tracking young adults to determine which factors are associated with the development of heart disease. Nutrition was one of the primary factors that was tracked using a food frequency questionnaire with dietician interview. They tested the subjects at the beginning of the study, at year 7 of follow-up, and year 20 of follow-up.

After tracking the subjects for almost 25 years, they found that 14.8% of subjects developed metabolic changes that indicated diabetes. Comparing the highest quintile of artificially sweetened drink use with the lowest quintile, there was a 129% increased risk for developing diabetic symptoms in the highest quintile. The use of saccharin was also associated with 120% increased risk of developing diabetes.

Is there more to this study that wasn’t highlighted in the headlines? I’ll cover that in Saturday’s Memo.

What are you prepared to do today?

        Dr. Chet

Reference:  Cur Devel in Nutr  https://doi.org/10.1016/j.cdnut.2025.107034

Why You Need a Plan

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I recently watched a documentary about a weight loss game show that was very popular about 25 years ago and lasted for 17 seasons. The show was one Paula and I watched for a number of seasons, but eventually we lost interest as the show became more bizarre and unrealistic. The documentary was challenging to watch for a variety of reasons; from the brutality of the trainers, the absurd challenges that demeaned the contestants as human beings, and the constant conflicts between contestants, it was not enjoyable.

According to the documentary, after the winner was announced, the people who had lost hundreds of pounds were left to fend for themselves. They essentially had left reality behind to live on less than 1,000 calories per day and to be able to exercise up to six hours or more a day for close to a year—then, nothing. No plan for how to transition to a normal life again. No explanation from dieticians or trainers how to adapt to maintain their weight loss.

In reality, it’s happening again right now with people who are using GLP-1 RA injections to control blood sugar and lose weight. If you’re going to try it, you should plan an exit strategy well before you’re done losing the weight, the same planning as what the weight loss contestants should have been provided.

How can you do that on your own if the healthcare professional doesn’t? Remember when I wrote about the physician who lost weight by eating the same portions as his wife was eating? I saw him again a week or so ago, and he’s maintained his weight loss well. The plan was to eat like his wife ate, and it has worked.

The Bottom Line

No matter what program or strategy you have to lose weight and get fit, you’ll be more successful at maintaining your weight loss if you work on the exit strategy before you’re even done losing the weight.

  • Are you willing to eat the same foods you ate during the process, or have you been depriving yourself of things you know you want to eat again? How can you fit your favorite foods into your new eating plan? The worst thing you can do is go back to your old way of eating.
  • Have you been doing extra exercise to get there? What are you willing to continue after you’re done? If you go back to your old way of life, you’ll probably go back to your old weight.

Whatever your strategy will be, it has to be something you’re willing to do for the rest of your life. You have the chance to plan ahead. That plan may change as you progress, but it’s easier to adjust a plan you’ve already worked out than to come up with one out of thin air. As the saying goes, “Failing to plan is planning to fail.”

What are you prepared to do today?

        Dr. Chet

Is Cold Pasta Healthier?

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Our grandson Riley has loved pasta since he started eating solid food (that’s him digging into his pasta at two; if his ear looks orange, it’s because his imaginary cell phone rang during dinner), and he often eats it cold. I mean refrigerator cold; he’ll eat it warm if we go out to a restaurant, but he prefers it cold. I don’t mean macaroni salad—I mean cold pasta, preferably with Riley sauce. The Riley sauce is my recipe created for him with a base of a marinara sauce; I grind up onions, garlic, mushrooms, carrots, zucchini, and beef with the grinding attachment for Paula’s KitchenAid mixer and add them to the base along with some additional spices. Then I slow cook it for a couple of hours. He eats that with a spoon (cold, of course) and doesn’t realize all the veggies he’s getting.

But it’s really the cold pasta that may be healthier for him. Why?  Doesn’t pasta increase blood sugar rapidly? Sure, if it’s hot. But when pasta is put in the refrigerator for a day or more, a process called retrogradation happens. As the pasta loses water, the remaining molecules lose their original structure and form a new structure. Those turn some of pasta’s sugar molecules into a resistant starch that passes through the body without being digested in the same way. When eaten cold like Riley does, that starch resists digestion until it gets down to the probiotics. There it can be turned into short-chain fatty acids instead of sugar molecules. Those fatty acids are much better for us for a variety of reasons.

As you celebrate the last summer holiday this weekend, keep in mind that pasta might be a dish best served cold. Have a fun Labor Day weekend, and please be safe if you’re traveling anywhere this weekend.

What are you prepared to do today?

        Dr. Chet