Tag Archive for: hazard ratio

BRI: It Just Doesn’t Matter

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Continuing our look at the BRI, the mathematician demonstrated that BRI is associated with body fat distribution. It makes sense; the waist measurement would provide an indication of fat around the waist. The next question is: would the BRI be a better predictor for cardiometabolic disorders than BMI?

BRI and Mortality

A group of researchers decided to use open-source data from the National Health and Nutrition Examination Survey database to examine the relationship between BRI and all-cause mortality. They coincided with the years that physical assessments were done including height and waist circumference; body weight was collected but not used in this instance. The time period began in 1999 and continued every two years through 2018.

There were two observations that were significant. First, in every demographic group, regardless of age, gender, or race/ethnicity, the BRI has increased during every examination period. As a country, the U.S. has gotten fatter. That matches every other measure such as body weight or BMI as well.

The second observation was that the hazard ratio (HR) increased as the BRI dropped below normal, then normalized when the normal BRI was reached, and the HR rose again as the BRI increased. Simply stated, there was an increased risk of mortality when people were too lean or too fat.

You may be wondering why I don’t give you a formula to do calculations for yourself. It’s very complicated and there are BRI calculators available on the website below. The main reason is that it just doesn’t matter—the BRI is no better at predicting mortality than the BMI. The researchers had the body weight data they needed to compare the BRI with the BMI directly. They just didn’t do it. However, looking at the mathematicians’ validation study, the categories of adiposity associated with BMI matches up quite well with the BRI and thus with body fatness. There’s no need for any more precision than is achieved with BMI.

The Bottom Line

It’s really the clinical use that seems to bother everyone, but with rare exceptions, the BMI gives an indication of body fatness. If physicians or other health care professionals cannot see the patient before them and realize they are too lean or too muscular to fit the typical interpretation of BMI, the fault lies with them, not the tool they are using.   

What are you prepared to do today?

        Dr. Chet

References:
1. JAMA. 2024; 332(16):1317-1318. 10.1001/jama.2024.20115
2. JAMA Netw Open. 2024; 7(6):e2415051. 10.1001/jamanetworkopen.2024.15051.
3. https://doi.org/10.1002/oby.20408
4. https://bri-calculator.com/#calculator

Do Weekend Warriors Improve Their Health?

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Let’s finish the week with a question no one asked but was the topic of a recent study: what’s better for your health—being a weekend warrior or working out according to established guidelines? The major component of the guidelines is more than 150 minutes of moderate to intense exercise a week spread out over most days of the week. Turns out, they are both effective, but let’s take a closer look.

The Study

The UK Biobank data are connected to the medical records of all people in the UK, making it an excellent source for studies. This observational study used data collected on close to 90,000 subjects who wore an accelerometer for a week sometime between 2013 and 2015; they were tracked for at least six years. Researchers tracked the diagnosis of over 678 conditions and compared those who exceeded the minimum of 150 minutes of moderate to intense exercise, either over a weekend or stretched over a week, with those who exercised fewer minutes.

The weekend warriors had reduced Hazard Ratios for 264 conditions and regular weekday activity had reduced Hazard Ratios for 205. Most of the benefits were associated with cardiometabolic metrics such as hypertension, resting heart rate, and type 2 diabetes. When compared head-to-head, there were no conditions where the weekend warriors and the regular exercisers differed.

What Should I Do?

I wouldn’t change anything you’re currently doing as long as you’re getting more than 150 minutes of moderate to intense exercise every week. We don’t know the activities involved in either—just that the accelerometer showed they were moving.

What it can mean is that for those who are playing basketball or soccer for a couple of hours a day on the weekends, you’re getting some benefit. It also means if you have a two-hour trail walk you like to do on weekends, it can help reduce your risk of cardiometabolic diseases.

The Bottom Line

What I really think it illustrates is that any movement is good movement, and if you can’t work in as much exercise as you’d like during the week, you can make up for it on the weekend. I would have liked to have seen the different activities involved and any orthopedic injuries associated with the activities, but let’s take the win. Just get moving and stay moving during the week or packed into a weekend. Or—maybe—both! Go get ’em, you warriors!

What are you prepared to do today?

        Dr. Chet

Reference: https://doi.org/10.1161/CIRCULATIONAHA.124.068669

The FFQ: Still Too Vague

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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

Is Red Meat Linked to Type 2 Diabetes?

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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

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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

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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

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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…

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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

Fish Oil: Reserve Judgment

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Let’s put the fish oil study from Tuesday in perspective. The most important thing is that observational studies such as these cannot demonstrate cause and effect. That’s not just a way to weasel out of making definitive statements; it’s because while fish oil supplements are associated in some way with atrial fibrillation in people who have no diagnosed heart disease, it may be something else that people who take fish oil supplements do that’s actually the culprit. Remember the hazard ratio (HR) was only 13%. What were the remaining 87% doing that was different?

The Problems

As I see it, these were the problems with this research paper.

Just as in the multivitamin study, researchers collected a whole host of dietary data and didn’t use much of it; they adjusted for those who ate oily and un-oily fish, but that was it. Fruit intake, vegetable intake, fiber intake, and a whole lot more dietary factors that have been shown to limit the development of cardiovascular disease were not considered. That may have impacted the HR.

The major problem was that they didn’t report the rate of AFib in those who did not take fish oil supplements. How can you not? What happens to those who do not take fish oil supplements could have provided comparison groups, which seems like a better analysis to conduct. No explanation. They just chose not to do it.

The final critique is that this study was conceived and executed by statisticians and epidemiologists. There were no nutrition experts on the team reported in the paper. I don’t know how that’s possible. If you’re considering a nutritional intervention, such as taking a fish oil supplement, there has to be someone who understands nutrition to consider other factors. It can’t be all statistics without thoughtful guidance.

The Big Question

How? How would fish oil supplements cause the development of AFib?

Research has shown that eating oily fish does not appear to cause AFib. Why would fish oil? The researchers cited a couple of possibilities having to do with an impact on channels that control electrical pathways but overall, no one has given any explanation.

This was not the first study that has examined fish oil supplements in large studies and found some relationship with AFib; there are also several that show no relationship at all. In this case, we have to reserve judgment because we can’t prove things either way.

The Bottom Line

What should you do? First, eat the healthiest diet you can and exercise regularly, because lifestyle is more important than supplements. Second, if you have already been diagnosed with CVD as I have—a stent more than 20 years ago—taking fish oil may be beneficial. If you’re under 60, it seems taking fish oil isn’t an issue and there’s no reason to stop. If you’re older than 60, should you begin to take fish oil supplements? It’s a matter of choice. I have to reserve judgment for now.

Next Tuesday is our primary election day in Michigan, and I’m taking the day off—I’m an election worker—but you’ll still get a Memo that goes into questions on this fish oil issue. There’s more to consider and I’ll let you know what those issues are.

What are you prepared to do today?

        Dr. Chet

Reference: BMJMED 2024;3:e000451.doi:10.1136/ bmjmed-2022-000451

Fish Oil and Atrial Fibrillation

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Researchers recently published an observational study on over 415,000 subjects in the UK Biobank database who took a fish oil supplement. During a follow-up period of almost 12 years, they statistically demonstrated a 13% increased hazard ratio (a measure over time of how often a particular event happens in one group compared to another group) in the development of atrial fibrillation in subjects. Atrial fibrillation is a type of arrhythmia, or abnormal heartbeat, that can result in extremely fast and irregular beats from the upper chambers of the heart. In those subjcts, there was a 5% increased risk of stroke.

The resultant impact was an attack on dietary supplements for being too easily available, leading to overconsumption, and questionable because of the lack of purity in dietary supplements. The Medscape Cardiology online section put out a video by a reputable researcher explaining who should take fish oil supplements. But if they’re so bad, why would she recommend them at all?

The other part of the results showed that if someone already had cardiovascular disease (CVD), the hazard ratio of developing major cardiac events was reduced if they took fish oil supplements. That’s why the expert made the video, taking the good and trying to make sense of it. Still, it gave the appearance of being a pitch for a pharmaceutical solution.

That’s the set-up for this week’s Memos. I’ll give you at least one of the questions you might have: Yes, this study tested only supplement use (and dietary intake) upon entrance to the study and nothing the rest of the 11.9 years, just like the multivitamin study from last week. But there’s so much more that I’ll cover on Saturday about the problems with this study. Just so you know, I’m still taking my fish oil supplements.

What are you prepared to do today?

        Dr. Chet

Reference: BMJMED 2024;3:e000451.doi:10.1136/ bmjmed-2022-000451