The FFQ: Still Too Vague

/in /by

I spent a long time examining validation and reliability studies on the Food Frequency Questionnaires (FFQ). It was interesting to compare the original validation studies with a new FFQ that was published in early 2024; researchers asked subjects in those studies that began decades ago to participate in this recent validation study.

The Stats

I learned more about a variety of statistics that I don’t typically encounter: coefficient of correlation, and then attenuated and deattenuated coefficient of correlations, and more. The researchers concluded that the “study showed that the FFQ used in prior studies has reasonably high reproducibility and validity in measuring food and food groups intakes among both women and men.” I disagree.

The coefficient of correlation is important (COC) because it gives an indication of the association of the variable with a standard, in this case a 7 Day Dietary Recall. The best COC is 1.0 or -1.0, which means it’s perfectly correlated or not correlated with the standard. A COC greater than 0.8 is considered a strong relationship, but a relationship of 0.6 – 0.79 is considered moderate.

The COC for most categories of food was well below 0.6. How can that in any way be valid? It may be reproduceable, but you’re reproducing the same mistake over and over again.

How Dangerous Is Meat?

High level analytics like this aren’t my area of expertise, but logic dictates that you can’t get precision even with large numbers of subjects. This is especially true when using FFQ data to correlate nutrition with disease. Remember the study on red meat intake and type 2 diabetes? The Hazard Ratio was only 10% per 100-gram serving of red meat. If the meat intake is moderately correlated, how much does any error of intake impact the HR?

Whether researchers are trying to estimate how much of each type of meat a person eats or trying to calculate the heme-iron content of that meat, the FFQ doesn’t have enough precision to be used in determining those values. Remember, the increase in HR was 10% per 100 grams—that’s 3.3 ounces—of unprocessed red meat per day. If a patty were 100 grams, a reasonable size, and you ate six patties every day, that would be 600 grams or over 1.5 pounds of hamburger patties per day. Would that raise the HR to 60% based on that single answer? What about a vegan who gets no heme iron? Would they never get type 2 diabetes? We know that’s not true either.

One more thing: People under-report what they eat. It can be 100 to 200 calories per day, or even up to 500 calories per day. No after-the-fact adjustment of the food intake can make up for that kind of imprecision.

The Bottom Line

What we’re left with is this: There may be a relationship between red meat, and subsequently, heme iron intake, and the risk of type 2 diabetes, but we don’t know how much. That’s about it. We’re going to need much better studies to nail that down before we make a pronouncement. For now, you’re probably safe eating red meat, especially if you keep this in mind: eat better, eat less, and move more.

What are you prepared to do today?

        Dr. Chet

References:
1. Am J Epidemiol. 1985;122(1):51–65.
2. Am J Epidemiol. 2024;193(1):170–179

The Problem with the Food Frequency Questionnaire

/in /by

I’ve made no secret that I don’t like Food Frequency Questionnaires. (FFQ). I understand why they are used; when a study may contain 500, 5,000, or 500,000 subjects, to do a dietary recall of the prior 24 hours, using a dietician to help determine portion sizes, would be close to impossible or very difficult at best. When nutritional research became the focus of examining dietary intake in populations across all ages, genders, and ethnic groups, the FFQ was developed. It was developed for the myriad studies of healthcare professionals; the first time I recall its use was the Women’s Health Initiative. Those studies have been going on for close to 50 years or more with repeated measures every few years.

Until very recently, they’ve used the exact same form of the FFQ that was developed 50 years ago. Because we covered studies on meat intake, let’s look at how the FFQ assesses intake of unprocessed meat. I’ll use only one item as an example: Hamburger (1 patty)

FFQ

The problem with this particular choice is that it doesn’t define what makes a patty either by grams or ounces. While I know that things have changed as it relates to our red meat intake, very few of us ever ate more than six hamburgers per day.

Those intake categories across the top apply to every food on the questionnaire. So tell me: how many fresh pears did you eat in 2023? How many tablespoons of jam or jelly? How can anyone answer these questions accurately?

It seems that this questionnaire was made in an era where people had more standardized food intake than they do today, although even back in the 1980s, the concept of family breakfast, lunch, and dinners seemed on its way out. These days we snack and graze, which makes it even harder to remember what we ate.

On Saturday, I’ll wrap this up on why the FFQ may provide a direction but isn’t precise enough to associate diet with disease in my opinion.

What are you prepared to do today?

        Dr. Chet

Reference: https://nurseshealthstudy.org/participants/questionnaires

Is Red Meat Linked to Type 2 Diabetes?

/in /by

The next study actually precedes the heme iron paper, not only in time but in size—with close to 2 million subjects! This was an attempt to check on whether red meat, chicken, or processed red meat, such as bacon and sausage, are associated with type 2 diabetes. This was a Herculean task that would never be possible without the type of computers available today; just examining the results of the observational studies alone was amazing.

The researchers used a statistical technique called a federated meta-analysis to test the relationship between meat consumption and type 2 diabetes that allows the nutritional data to be analyzed while preserving the anonymity of the subjects. One of the problems was that the data for meat intake had to be standardized among the 31 countries covering the Americas, Eastern Mediterranean, European, South-East Asia, and Western Pacific.

With 1.9 million adults selected for the study, there were just over 107,000 people diagnosed with type 2 diabetes. The median follow-up time was 10 years. The range of meat consumption in all categories was as little as 0 grams up to 110 grams per day. One thing that surprised me as I looked at the medians was that the European processed meat intake far exceeded that of the U.S.—Americans love their hot dogs and cold cuts and sausage and bacon, but apparently not as much as Europeans do.

They found that eating more of each type of meat increased the diagnosis of type 2 diabetes. The Hazard Ratios were:

  • 10% greater risk for each 100 grams of unprocessed red meat
  • 15% greater risk for each 50 grams of processed red meat
  • Only 8% greater risk for every 100 grams of chicken

The increased risk was found in North America, Europe, and the Western Pacific regions. Repeated covariates such as age, gender, or BMI were tested to explain the differences with other regions, but no clear answers emerged. The conclusion? Eating red meat is a risk factor for developing type 2 diabetes across all populations, and processed meat even more so.

Why Meat?

I often criticize these types of studies because they don’t give any reasons or even guesses as to why the results turned out as they did. They couldn’t explain it but gave one possibility that many people don’t consider: red meat and chicken with skin contains fat, and processed red meat has other chemicals used in processing, but what they have in common is protein. If people aren’t eating enough carbohydrates, they are more likely to make glucose from the amino acid remnants of the protein. That’s why people who claim to eat few carbs and starches will end up with prediabetes and fatty livers. I give the authors credit for that.

The real problem, in my opinion, goes back to data collection: almost all studies used a food frequency questionnaire. That’s the topic I’m going to cover next week.

What are you prepared to do today?

        Dr. Chet

Reference:  Lancet Diabetes Endocrinol. 2024; 12: 619–30

Iron from Meat and Type 2 Diabetes

/in /by

The abstract begins simply enough: “Dietary Haem iron intake is linked to an increased risk of Type 2 Diabetes.” Haem iron is another word for heme iron, iron sourced from animal meat. But let’s get back to the statement. The first question that pops into my mind is this: how did they measure iron intake from all sources, especially when you consider the scope of the study?

The research team examined data from over 200,000 potential subjects from three large studies of healthcare professionals; some of the subjects were followed for as long as 36 years. Researchers wanted to examine associations between iron intake from all sources and the risk of type 2 diabetes. They also examined blood markers in a subset of close to 38,000 subjects: insulin, lipids, inflammation, and uric acid levels.

They found that heme iron intake resulted in a Hazard Ratio of 26% increased risk for the development of type 2 diabetes when comparing the highest quintile with the lowest quintile of heme iron intake. The heme iron intake was also correlated with poor blood profiles such as high insulin, hs-C-reactive protein, and lipid levels. Nothing from non-heme sources.

Is it time to reduce meat intake? That’s not my initial question. My question is how’d they do that? How did they measure the heme and non-heme iron levels in over 200,000 people? We’ll hold on that for now and look at a study with almost 2 million subjects on Saturday.

What are you prepared to do today?

        Dr. Chet

Reference: https://www.nature.com/articles/s42255-024-01109-5

Nutrition Research: Incomplete

/in /by

In July and August, I wrote about recently published studies on multivitamins and mortality and fish oil and atrial fibrillation. My criticism of those observational studies was because the analyses of the data were incomplete, in my opinion. Here’s how the study we just finished on quercetin and irritable bowel did the correct analysis.

Researchers focused on the subjects with an irritable bowel condition and examined a single nutrient. They already knew that increased fruit and vegetable intake benefitted people with irritable bowels; they specifically examined the quercetin content of those vegetables and fruit to see if subjects who ate those foods needed fewer enterotomies and had lower mortality. They did. This is the way nutrition research should be done.

That’s exactly what they did not do in the multivitamin and fish oil studies. It isn’t like they didn’t have the data; one of the studies used the exact same database of subjects with the nutrition data already collected. They could have analyzed by nutrient, whether it was a macronutrient such as protein, carbohydrate, and fat; by the source of the protein, fat, and carbohydrate intake; or by specific nutrients such as calcium, beta-carotene, or type of fish oil. I could go on, but the point is they could have done more. But as I suggested, when physicians and statisticians are the only experts used—without nutritionists and dieticians—they apparently didn’t know the correct questions to ask.

As a result, we’re now stuck with physicians and other healthcare professionals questioning the use of multivitamins and fish oil. Experience tells me that will be hanging over our heads for years.

During the conclusion and recommendation section of every study, they always finish the observational studies with something like “This study doesn’t provide cause and effect; we need randomized controlled trials to test these findings.” I submit we need more thoughtful analysis of the data used in these studies. The way I see it, those studies were disasters, and there are more to come in the near future. Next week we’ll look at a study that condemns green tea extract and turmeric.

What are you prepared to do today?

        Dr. Chet

Quercetin and Irritable Bowel

/in /by

In the study I talked about on Saturday, the typical way of analyzing this data is to divide the group into segments by a specific variable and then compare the hazard ratios. In this case, the variable was quercetin and they chose to divide the subjects up by quartiles. During the follow-up time of nine years, there were 193 enterotomy events and 176 deaths. Compared with participants in the lowest quartile, those with irritable digestive conditions in the highest quartiles of quercetin intake were associated with a 54% lower risk of enterotomy and 47% decrease in all-cause mortality. In simpler terms, it cut the risk of a serious outcome by half. The relationship was the same regardless of the type of irritable bowel condition for both enterotomy and all-cause mortality with the exception of mortality of ulcerative colitis.

What does all this mean? There’s some type of positive relationship for people with serious digestive disorders who eat plant foods that contain quercetin. While interesting, this type of study doesn’t provide cause and effect—just a positive relationship. Stated simply, as people increase their quercetin-containing plant intake, the risk of having issues with serious outcomes from digestive disorders decreases. Quite correctly, the researchers recommend further research in clinical trials before the results can be confirmed.

The message: eat your vegetables and fruit. Here is a list of the top five vegetables and fruits containing quercetin. For vegetables:

  • Hot peppers (but please, no Carolina Reaper or anything that strong)
  • Broccoli and other cruciferous vegetables
  • Red onions
  • Herbs such as dill and cilantro
  • Capers

For fruit:

  • Apples
  • Tomatoes
  • Dark-skinned grapes
  • Green tea
  • Red wine if you drink alcohol

Maybe there is something to the old saying “an apple a day, keeps the doctor away.” If it keeps the heartburn away, that would do it for me.

You may think we’re done. Remember that Memo on making a single decision that has a long-term impact? I’ll tie that and this study together on Saturday.

What are you prepared to do today?

        Dr. Chet

Reference:  The Journal of Nutrition. 2024;154(6):1861-1868

If You Have an Irritable Bowel…

/in /by

It seems many people experience digestive issues, from constipation, heartburn, and many types of irritation in their bowels. Many people are avoiding some food or ingredient—from gluten, most often found in wheat and bread products, to certain ingredients that are found in food, at least the foods that are available today. I have a slight hiatal hernia, a tear in the lining between my stomach and my lungs, and that can cause reflux; eat too much and I pay the price. Based on a recently published study, those of us who have any type of irritated digestive system just might find the answer in the produce section of our markets.

Researchers used the UK BioBank database to find subjects who had completed five of the 24-hour dietary recalls in a follow-up period of nine years. With that criterion met, subjects were recruited through electronic medical records as having conditions related to the digestive system under the umbrella term total irritable bowel. The researchers used the dietary history to identify all the foods the subjects ate that contained the phytonutrient quercetin; prior research had shown that the consumption of fruits and vegetables with that nutrient showed some benefit for people with digestive issues. The researchers wanted to confirm or refute those observations.

The researchers were able to identify 2,293 participants with serious digestive issues in the database. Diet information was collected using 24-hour dietary recalls; the researchers determined quercetin intake based on nutrient databases that estimated the amounts in the foods consumed.

The researchers were interested in two specific outcomes: enterotomy (the surgical opening of the digestive system to repair damage) and all-cause mortality. The researchers analyzed the data to estimate hazard ratios: the probability that someone will experience those outcomes over the follow-up time, which again, was over nine years. What did they find? I’ll let you know on Tuesday.

What are you prepared to do today?

        Dr. Chet

Reference: The Journal of Nutrition. 2024;154(6):1861-1868

One Decision, Lasting Impact

/in /by

I love behind-the-scenes shows: how do things work? That probably explains why I like to dig into health studies the way I do. My latest fascination is with a show on the National Geographic channel called Disaster Autopsy. Several scientists examine man-made disasters to find out what went wrong. Most of the time, it comes from a single decision or single event that was unforeseen but made a lasting impact. The disaster didn’t happen right away; in some cases, it was decades later.

Does this apply to our body as well? You may think I’m talking about a single decision you made related to health—one decision made years earlier, that could seal your fate. Health is not quite that simple with multiple variables that interact. Still, after reading the Memo of the lifestyle factors that influence a healthy brain, have you made any changes?

The science of health can do the same thing: have an impact that lasts. The next three Memos are related to the choices that researchers can make by looking at the data in depth instead of superficially; they can impact health recommendations for decades. At the same time, we’ll find out the benefits of a phytonutrient called quercetin.

What are you prepared to do today?

        Dr. Chet

Research Update: Cancer and Diet

/in /by

A recent paper used an interesting approach to treat pancreatic cancer using a high-fat diet. That flies in the face of the typical approach: “If it was ever alive, don’t eat it.” In other words, a vegan diet. I’ve reviewed fasting prior to cancer treatment, which demonstrated improved outcomes for those who fasted, but this diet is radically different.

The Study

This study was all about finding the weakness in a defensive mechanism and attacking it.

Researchers were studying the mechanism that cancers use to get energy. The thought is that cancers use sugars and carbs, but cancer’s need for fuel to grow isn’t that limited. Researchers were studying how cancers switch to using fat as a fuel when there are no carbs available. Just like with the keto diets, the liver, and subsequently cancer cells if present, switch to using fat as a fuel in the form of ketone bodies. The protein that stimulates this switch is called eIF4E.

Researchers were able to find a current chemotherapy drug called eFT508 that blocked the ability of eIF4E to turn on the fat metabolism pathway. However, that didn’t stop the cancers from growing—they used other fuels such as carbs. But when they first treated the cancers with the chemotherapy drug that prevented the cancer from using fat as a fuel, then put them on a high-fat diet, the tumors all shrank.

In this study, the type of cancer was pancreatic cancer, one of the deadliest. This was a rodent study, but the chemotherapy drug is already approved for use in humans. Clinical trials are surely to follow in humans.

The Bottom Line

The authors speculate that cancers have more than one weakness that can be exploited with a combination of dietary and pharmaceutical interventions. Their breakthrough came almost 15 years after discovering what blocked the fat metabolism pathway. To me, this is one of the most exciting studies I’ve read in a long time. Just remember that this was one potential treatment for one type of cancer, but it represents hope.

I’ll be back in a week with a new Memo. If you’re here in the U.S., enjoy the final holiday of the summer—but don’t forget to eat your fruits and vegetables.

What are you prepared to do today?

        Dr. Chet

References:
1. https://medicalxpress.com/news/2024-08-fasting-ketogenic-diet-reveals-vulnerability.html
2. https://www.nature.com/articles/s41586-024-07781-7

Research Update: Preventing Dementia

/in /by

How many of you have had this experience: “Why did I walk into this room—what was I supposed to do?” I’ll bet you begin to wonder, “Am I losing it?” I don’t think so, but just to be sure, I decided to present the Lancet Commission’s latest update for dementia prevention, intervention, and care. They’ve published a list of lifestyle habits that, based on research, are associated with preventing dementia. The 2024 report added two more lifestyle objectives.

I’ll present the 13 recommendations without saying how to achieve those habits with the latest additions at the end. For now. But over time, I’ll address those in future Memos, webinars, and audios as I review the complete research. I think it’s important to know the what to begin with. Remember, these are life-long habits.

Specific Actions to Reduce Dementia Risk

  • Ensure good quality education is available for all, and never stop learning throughout life.
  • Encourage exercise because people who participate in sport and exercise are less likely to develop dementia.
  • Maintain a healthy weight and treat obesity.
  • Make hearing aids accessible for people with hearing loss, and decrease harmful noise exposure to reduce hearing loss.
  • Treat depression effectively; I would add early as well.
  • Encourage use of helmets and head protection in contact sports and on bicycles.
  • Reduce cigarette smoking by any practical means.
  • Prevent or reduce hypertension and maintain systolic blood pressure of 130 mm Hg or less from age 40.
  • Reduce high alcohol consumption.
  • Prioritize age-friendly, supportive community environments, and housing to reduce social isolation by facilitating participation in activities and living with others.
  • Reduce exposure to air pollution.
  • Make screening and treatment for vision loss accessible for all.
  • Detect and treat high LDL cholesterol from midlife.

The Bottom Line

These 13 steps to reduce the risk of developing dementia are independent of genetic factors. That makes sense; we can have the worst set of genes, but if they’re never expressed due to a good lifestyle, the development of dementia can be reduced or at least delayed. We’ll explore how we can do these things in the future, but you probably see the place to begin in several habits: Eat less. Eat better. Move more.

What are you prepared to do today?

        Dr. Chet

Reference: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01296-0/abstract