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Issue #49 (November 2018)

From the Editor

Volume 1

In the last volume of the NERD, I gave a quick overview of the Vitamin D and Omega-3 Trial (VITAL). Another major trial examining omega-3 fatty acids was also published In the same issue of The New England Journal of Medicine as VITAL, called REDUCE-IT (standing for “Researchers Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial”). It found some big results and made some headlines. This is one we probably won’t cover in full detail, since it doesn’t involve the kind of fish oil you can just get off the shelf, but instead pharmaceutical grade fish oil that exists as a drug, not a dietary supplement, at least in the U.S. Since we won’t be covering this study in detail, I’d like to give you a quick rundown of REDUCE-IT, as well as briefly comparing some aspects of it with VITAL.

In terms of the intervention, REDUCE-IT used icosapent ethyl, which is an ethyl ester of EPA, one of the two big types of omega-3 fatty acids found in fish oil (the other being DHA). As far as I know, there’s nothing super-special about icosapent ethyl versus other forms of EPA, like the triglyceride or free acid forms — it gets cut up in the gut to EPA anyway. This form of EPA is more of a byproduct of the process of getting EPA to very high concentrations— much higher than you can find in supplemental form. REDUCE-IT used 2 grams of this form of EPA twice a day for a total of 4 grams per day. That’s almost nine times the amount of EPA used in VITAL. So, we’re talking a lot of EPA here — much higher than most other trials have used, and more than I could comfortably take using supplemental fish oil. Just thinking of the fish burps alone that that many capsules would cause… ugh.

The population of REDUCE-IT is also worth mentioning. Most of the people enrolled already had cardiovascular disease, and all were on a statin of some kind that had their LDL-C well under control (the majority of people had LDL-C levels under 100 mg/dL). Thus, REDUCE-IT tested adding either high-dose modified EPA or a placebo to a statin in people at high risk for CVD, but who were being treated well. The placebo in this case was mineral oil. That could be a problem, since mineral oil can affect drug absorption and may impact cardiovascular risk markers. And, indeed, REDUCE-IT’s placebo arm saw their triglycerides and LDL-C rise during the course of the study, which suggests that mineral oil may have had some negative effect, whether on its own or due to interference with statin absorption.

This makes me think that the effects seen in REDUCE-IT are larger than they would otherwise be if another placebo were used… but those effects are still impressive: a 25% reduction in the primary endpoint, which was a composite of a bunch of bad cardiovascular outcomes. The risks of the individual outcomes that made up the composite pretty much tracked the composite, which makes it look like this composite endpoint isn’t just a statistical trick to get a positive result — super-high dose modified EPA really seems to work.

While the lower dose used in VITAL didn’t work as well, there were signs of some effect, as I described last time. On the other hand, the news for vitamin D supplementation keeps getting worse, as you’ll discover in this volume. Read on...

Gregory Lopez, MA, PharmD
Editor-in-chief, Nutrition Examination Research Digest

Volume 2

I’m a little bit of a luddite when it comes to portable tech. I resisted the smartphone trend for as long as I could, and, up until this month, I’ve also resisted the wearables trend for the same reason: I didn’t quite see their utility. I was definitely wrong about how useful smartphones are, at least as long as I’m selective about what apps I install. However, I’m still up in the air about wearables.

One reason is that wearables just seem like yet another way to distract me for no good reason. But, as I quickly learned with smartphones, being super-conservative about what notifications I let through and what apps are installed solves that problem. Also, the specific wearable I got is more of a fitness tracker than a smartwatch anyway. But the question that’s still on my mind is whether or not it’s actually telling me anything actionable. The prime example of this is its sleep-tracking feature, which look impressive at first blush. The tracker’s able to break down total time slept into deep and light sleep, and time spent in REM. But I’m still not exactly sure what I can do with that information.

It also gives me an estimate of calories burned per day, which in theory could be useful. For instance, I could use the estimate of calories burned plus changes in my weight to see how many calories per day I should remove from my daily diet to lose weight. That seems actionable, except the estimate the wearable is giving me for daily calories burned seems way off base — I literally laughed the first time I looked at its estimate! My intuition that’s it’s off track is backed up by some recent research[1] showing that these devices don’t do well at estimating total energy expenditure.

But all of this may be okay, since the main fitness-related reason why I got it was to track my total active minutes, and despite minor heart rate inaccuracies, it does pretty well with this as far as I can tell. Active minutes are a major part of the Physical Activity Guidelines for Americans, which has recently been updated by The Department of Health and Human Services for the first time in 10 years. You can check out the summary for yourself here, or the full version here. The basic guidelines for most adults haven’t changed: at least 150 minutes per week of moderate intensity activity (or 75 minutes at high intensity, or a mix) is recommended as the minimum people should strive for, with higher amount of activities bringing even more benefit. At least two sessions of strength training per week is also recommended. What’s new is the elimination of the recommendation that bouts of activity should be at least 10 minutes long to count, along with guidance for preschool age children and a discussion of more benefits for certain types of disease prevention (e.g., exercise lowers risk for a few more cancers and Alzheimer’s disease). There’s also more talk about how activity helps with pain levels and function with some chronic diseases, too.

We do our best not to overhype things at Examine.com. But, while I’m still skeptical of my fitness tracker’s utility, I’m not skeptical of physical activity’s benefits — it can’t be hyped enough in my humble opinion. It’s one of the most important things people can do to get and stay healthy.

Gregory Lopez, MA, PharmD
Editor-in-chief, Nutrition Examination Research Digest

See other articles in Issue #49 (November 2018) of Study Deep Dives.