Tag Archive for: hazard ratio

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

Nothing to Fear from the Multivitamin Study

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If you’re concerned about taking your multivitamin, I think you can lower the concern. Is it still possible that there may be individuals who may have a unique set of genes and covariates that may increase the risk? Sure, it’s possible, but this study brought us no closer to finding out if that’s true. Here’s why.

The Issues with the Study

The problems lie in what the researchers didn’t do.

While the researchers used 13 different covariates, they didn’t break the data down by macronutrient or micronutrient. They used the Healthy Eating Index, but that ranks the quality of the diet from 0 to 100; that’s not the same as breaking the subjects’ diets down by intake of vegetables or antioxidants. It’s possible that someone who ate more vegetables could have higher antioxidant levels, which could contribute to getting too much of a nutrient by taking a multivitamin. The same would be true if they also were taking a complete multivitamin-multimineral and getting too much calcium or iron. That might have given valuable information to the people most at risk if there were such a relationship.

The researchers also did not give any explanation for mechanisms through which a multivitamin could increase mortality. That’s not unusual, because they didn’t examine any nutrient factors—but still, what was the point of saying there may be an increase in mortality, but nothing more than that?

The most likely explanation is that the results happened by chance because they tested multivitamin intake only twice early in the studies. Think of what you were eating 20 years ago. Has that changed? It’s reasonable to expect that some peoples’ habits changed, just as their dietary intake may have changed. We don’t know because they couldn’t go back and do the questionnaires every year or two, or even every five years. They suggest that this was a problem due to the latency of the data, and they were correct in my opinion.

The Bottom Line

This study illustrates the problem with going back to analyze data collected decades ago: you’re limited by the data you have rather than actually planning the study from the beginning. It’s an interesting observation after chunking lots of numbers, but it’s not meaningful in the real world due to the lack of ability to do an adequate analysis of the data.

What are you prepared to do today?

        Dr. Chet

Reference: JAMA Network Open. 2024;7(6):e2418729.

Will Taking a Multivitamin Increase Your Risk of Death?

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Close to a month ago, the health headlines were full of warnings about multivitamins. A long-time researcher even did a video to explain the study. This headline was based on a study that demonstrated an increase in Hazard Ratio if a person took a multivitamin every day, compared to occasionally or never. On the face of it, this seemed to be a compelling study. Data were combined from three large studies that totaled over 390,000 participants. The data were taken from health and nutrition questionnaires first given more than 20 years ago, with the mean follow up time of about 21 years. The questionnaires asked about a variety of demographic data as well as health and nutrition habits; the nutrition data were the old-style FFQ form.

After analyzing the data, researchers found a 4% increase in mortality risk in those participants who took a multivitamin every day compared to those who did not. Should you be worried? Aside from the number of covariates they considered, and you know how those combinations can add up, there were at least two problems. I’ll cover those on Saturday.

The Winners of the Challenge

Everyone who responded to the 4th of July challenge did an amazing job—no one had fewer than 20 vegetables and fruits. Where it got a little murky was in the herbs and spices; I’ll take the blame for that as I didn’t explain it as well as I should. For the overall total, I’m going to declare a tie between RE and KB; they each had close to 60 foods that qualified! For vegetables alone, VK topped the list with 23 and MW topped the fruit list with 13. Great job, everybody!

What are you prepared to do today?

        Dr. Chet

Reference: JAMA Network Open. 2024;7(6):e2418729.

Nutritional Epidemiology: Specification Curve Analysis

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Did you look up quadrillion? It’s a 1 with a whole lot of 0s—15 to be exact.

When I finished Saturday’s Memo, the researchers had chosen an area of nutritional epidemiology to focus on: the analytics used to analyze the data. They began with the premise that there are many ways to analyze any data set. They then identified published research studies that examined the consumption of red meat and mortality. They identified 15 publications reporting on 24 studies that examined the effect of red meat on all-cause mortality.

They weren’t doing a meta-analysis to see all the results of all the studies combined; they used a newer technique called specification curve analysis. They identified the type of data used in the analysis, the number of variables, the number of covariates, as well as demographic data. From that information, they then calculated the total number of ways each data set could be analyzed—the specification curve analysis. Turns out that number is 10 quadrillion! That exceeds the capacity of the computing power of a small country, and I can’t even imagine how much electricity that would consume.

They decided to take a randomized sample of the possible ways to analyze the data with specific variables and covariates in each and came up with 1,440 different approaches to analyzing the data. They ran additional tests on the data and eliminated 232 approaches because the data exceeded norms.

Then they ran the remaining analytic approaches on data from several years of the NHANES study. What did they find?

  • The median hazard ratio (HR) was 0.94 for the effect of red meat on all-cause mortality. That means the mortality risk was decreased 6% if the subject ate red meat.
  • HRs ranged from 0.51 to 1.75; 435 approaches yielded HRs more than 1.0 (increased risk) and 773 less than 1.0 (decreased risk). Most analyses showed that eating red meat reduced the HR, and thus reduced the risk of dying.
  • Of all the results, 48 (almost 4%) were statistically significant; of those, 40 indicated that red meat reduced all-cause mortality and 8 that red meat increased all-cause mortality.

Does this mean that eating red meat decreases your risk of dying early? We’re not done yet. We’ll put it all in perspective on Saturday.

What are you prepared to do today?

        Dr. Chet

References:
1. https://www.sensible-med.com/p/the-definitive-analysis-of-observational
2. Journal of Clinical Epidemiology 168 (2024) 111278

Do Artificial Sweeteners Increase Cancer Risk?

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Last week, my health news feed filled up with headlines that almost all sounded like this: “Artificial Sweeteners Linked to Higher Cancer Risk!” This isn’t the first study to suggest that relationship and it won’t be the last. This French epidemiological study of over 100,000 subjects collected data for more than seven years. One of the things I almost always criticize is data collection using food frequency questionnaires. Not this time.

The subjects completed at least two food diaries per year. Portions were assessed by comparing with pictures of portions sizes. What they did particularly well is to list all the foods that contained artificial sweeteners, including all brand names; then they tested most of the foods in the lab to verify the presence of artificial sweeteners. Researchers collected as many confounding variables as they could to account for everything that contributes to cancer.

After the statistical analysis, the overall hazard ratio demonstrated a 13% increase in the risk of cancer. Aspartame and acesulfame potassium were the artificial sweeteners with the highest hazard ratio among all those tested. Based on this information, do we need to avoid artificial sweeteners or at least lower the amounts we consume? I’ll talk about that Saturday.

What are you prepared to do today?

        Dr. Chet

Reference: https://doi.org/10.1371/journal.pmed.1003950