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Issue #48 (October 2018)

From the Editor

Volume 1

In my last editor’s intro in NERD #47, volume 2, I talked a little bit about an article we reviewed looking at how fruits and veggies compared to whole and refined grains in their impact on markers of inflammation and the gut microbiome in people with overweight or obesity. I found the results a little hard to interpret, since the way the paper reported the results focused on changes within each group, as compared to changes between groups.

While looking at within-group differences present part of the equation, they don’t show the whole picture in a controlled trial, since you lose information from the control group — even if inflammatory markers decrease when you give people, say, whole grains, you can’t be sure this change isn’t due to other confounding factors. But these confounding factors should have a similar impact in the control group, assuming the trial’s well randomized. So, comparisons to the control group allow for a lot more confidence that any changes you see in treatment groups are due to the intervention since these confounding factors are more likely to wash out in the comparison.

I wrote the authors asking for the statistics and they were kind enough to reply. After looking at the statistics with a focus on between-group comparisons, it looks to me that out of the four major inflammatory markers they measured, there was a clear, strong impact on lipopolysaccharide binding protein (LBP) for adding both fruits and veggies or whole grains to the diet compared to control. However, fruits and veggies didn’t clearly differ from whole grains when looking at inter-group comparisons — they both had a similar benefit. LBP is part of our immediate immune response against Gram-negative bacteria that live in the gut, like E. coli. Decreased LBP suggests that fruits and veggies or whole grains may improve the integrity of the intestinal wall compared to refined grains. Besides that, there were no significant between-group differences, suggesting to me that the study couldn’t really detect an impact on the other inflammatory markers that were measured.

Since this is a pretty small study, this isn’t strong evidence of no impact — there’s room for more evidence that can show a difference. In fact, some already exists for both fruits and veggies[1] as well as whole grains[2]. There’s also some room for disagreement with my take on the stats, too, since statistics aren’t always clear cut. But in order to leave that room, sharing data and details that may not be in the journal article is essential, and I appreciate the time the authors took to share theirs with me.

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

Volume 2

The results from a major clinical trial examining two popular supplements have recently been released in the New England Journal of Medicine. We may give full coverage in a future NERD, but I’d like to give you a quick summary.

The Vitamin D and Omega-3 Trial (VITAL) took a good look at the impact of those two supplements on cardiovascular disease and cancer. Over 25,000 people over age 50 (55 for women) were recruited for the trial, who were randomized to placebo, 2,000 IU of vitamin D daily, 1 gram of fish oil containing 460 mg EPA and 380 mg DHA daily, or both. They were then followed for around five years to see how supplementation affected cancer and cardiovascular outcomes. The primary outcome for cancer was getting any type of invasive cancer. On the cardiovascular side, the primary outcome was a composite of heart attack, stroke, and cardiovascular death. Sometimes composite endpoints can be misleading if the outcomes being thrown together aren’t of the same severity, or the risk of one component goes down while another’s goes up. However, this doesn’t look to be a problem here. A bunch of secondary outcomes were also measured, and the results were published in two papers: one for vitamin D and one for fish oil.

Let’s go over the vitamin D results first. The study found no benefit for getting cancer overall — supplementation had no statistically significant effect on the primary outcome. None of the preplanned secondary analyses came up with much either. However, death rate was slowed significantly in the vitamin D group when the first two years of follow-up were excluded. This analysis wasn’t preplanned; however, the preplanned death rate which took all the data into account was only barely not statistically significant. This tells me that vitamin D’s effect on cancer death rate is something that deserves to be looked into further. But things were much less promising in terms of vitamin D’s cardiovascular effects; it was pretty much null. Baseline vitamin D status didn’t seem to matter for either outcome; even for people with vitamin D deficiency, there were no strong, discernible effects.The number of people who were vitamin D deficient was relatively small though, leading to wide error bars, so moderate effects can’t be completely ruled out for people with deficiency.

Fish oil was pretty much a wash cancer-wise; nothing much of significance was found. But, while the primary cardiovascular outcome was also negative, there were some promising secondary cardiovascular findings; heart attacks, deaths from heart attacks, and coronary heart disease all improved with fish oil supplementation. Many of these findings may be driven by people who eat less than 1.5 servings of fish per week, who seemed to benefit more from fish oil. This group saw a reduced rate of major cardiovascular events (the primary outcome) as well as reduced all-cause mortality.

While VITAL provides strong evidence that vitamin D and fish oil aren’t panaceas, it also can help guide future research, as well as provide some guidance concerning who these supplements may work better for, such as fish oil for people with low fish intake.

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

See other articles in Issue #48 (October 2018) of Study Deep Dives.