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Issue #43 (May 2018)

From the Editor

Volume 1

In this volume, one of the topics we dip our toes into is caloric restriction’s effects on markers related to longevity. I say “dip our toes” because the research we cover is just one of many publications coming from a pretty major project in the area: the Comprehensive Assessment of the Long-Term Effects of Reducing Intake of Energy (CALERIE). Also, this is a huge field, and the paper we review covers just one small aspect of it. Since we don’t chat too much about CALERIE as a whole in our review, I thought I’d use my soapbox this month to give a very brief, necessarily oversimplified introduction to it.

This project was funded by parts of the National Institutes of Health, including the National Institute on Aging. Its goal is to measure the effects of calorie restriction on multiple outcomes. Unfortunately, it’s the nature of the beast that many of these outcomes are biomarkers. While RCTs that look at what people really care about when restricting calories for longevity (namely: lifespan) would be nice, they would be extremely hard to conduct well, take a long time, and would be really, really expensive.

Notice that I’ve been calling CALERIE a “project” so far. That’s because it’s not just one RCT, but instead a series for trials consisting of two main phases. The first phase, CALERIE-1, consisted mainly of three pilot studies for up to a year that looked at the safety of inducing a caloric deficit through diet, exercise, or both. However, it also looked at some metabolic outcomes.

These findings informed CALERIE-2, which was a two-year trial aiming at (but ultimately missing) a 25% caloric deficit. The researchers chose a two-year timeframe because CALERIE-1 demonstrated that a lot of the metabolic outcomes they were interested in didn’t change as much as they anticipated over shorter timeframes.The main goal of CALERIE-2 was to see if the metabolic changes related to longevity that are found in animal studies are also found in humans. Basically, the thinking is that if human biomarkers behave in a similar way to model animals whose calories are restricted, and calorie restriction increases those animals’ lifespans, then we can be more confident that caloric restriction could also influence human lifespan. While this reasoning is less direct than running a clinical trial looking at the hard outcome of lifespan, it is much more feasible.

The study we cover in this volume is a substudy of CALERIE-2, which looks at more biomarkers related to two main theories of aging, as well as teasing apart changes in resting energy expenditure a little more. It serves as a hypothesis test of sorts to see if these theories of aging apply to humans, at least in the medium-term.

Hopefully this (too) quick overview puts the study we review here in a little more context. Read on to discover whether the study’s main hypotheses stood up to the test.

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


Volume 2

In this volume, we report on an important meta-analysis which comes to the disappointing conclusion that nitrates don’t do much to improve performance in athletes. The study did find a small improvement in time to exhaustion in non-athletes, though. But that was the only major positive finding. If we take these results at face value, they seem to imply that non-athletes can use nitrates to improve endurance, but everyone else shouldn’t bother.

I’d like to use my soapbox this month to actually argue the opposite: that competitive athletes may still want to consider using nitrates (or at least beetroot juice), while non-athletes shouldn’t bother. Big caveat: I am not an athlete or a coach, so take what I’m saying here with a huge grain of salt. This is meant to stimulate some thoughts about these results rather than coming to A True Conclusion.

So why would I say that non-athletes for the most part shouldn’t bother with nitrates? It comes down to use case and effect size. First, the effect size is small, so non-athletes probably won’t get much of a boost. But more importantly, I can’t think of many cases where non-athletes would want a small boost in endurance. Perhaps it’s my lack of imagination, but the only two cases I can think of is if a non-athlete is entering a competition where small boosts in endurance would matter, and during regular training to push their endurance to higher levels. The former case seems relatively rare to me, and in the second case, perhaps being able to push a tiny bit further during training can lead to slightly quicker improvements in endurance. But, unless there’s a big rush, I’m not sure this would be useful, either, since it would take a while for these small boosts to build up significantly over time. So, either way, nitrates don’t seem too useful for non-athletes except in rare circumstances.

Moving on to the case of athletes — why would I think that they might still want to consider taking nitrates when no effect was found? One part of the answer comes down to error bars and, again, use case. For competitive athletes, small differences during competition matters. And a close look at the error bars for nitrates’ effect in athletes shows that they don’t preclude very small effects. Thus, nitrates may be worth a shot for competitive athletes. A closer look at the data also shows something interesting: the only study that went into this meta-analysis that showed a clearly positive effect in athletes had them taking beetroot juice with negligible nitrate levels. We talked about the fact that nitrates may not be the only performance-boosting compounds found in beetroot in NERD #38, volume 2; betalains may play a role, too. While it’s still a little too early to tell, even if nitrates aren’t very effective, beetroot may be.

Combining these two lines of argument leads me to think that competitive athletes may want to still continue supplementing with nitrates (or at least beetroot), but that it isn’t really worthwhile for non-athletes except under specific circumstances.

Agree? Disagree? Feel free to chat about it in the private NERD Facebook forum!

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

See other articles in Issue #43 (May 2018) of Study Deep Dives.