Krill oil raises metabolic risk

mikeccolella · June 30, 2016

http://ajcn.nutrition.org/content/early/2015/05/27/ajcn.114.103028

This study suggests krill oil may not be a good option.

Dean Pomerleau · June 30, 2016

Interesting Mike. But actually not that surprising when you think about it.

The study Mike points to [1] was actually a pretty good design, as nutrition/supplement studies go. The researchers recruited 50 overweight but otherwise healthy men to participate in a cross-over design experiment, allowing each to serve has his own control. During one 8-week period each subject received 5 one-gram capsules per day containing a mixture of krill (88%) and salmon (12%) oil. After an 8-week washout, each man then received 5 one-gram capsules containing canola oil as a control for another 8-week period. The order of the two conditions was randomized per subject, so that there weren't any ordering effects.

Surprisingly (at least to the researchers) at the end of the period when the men took the KS oil, they had 14% lower insulin sensitivity (P < 0.05) relative to when they were taking the canola oil capsules. After the researchers factored out the likely beneficial effects of EPA/DHA on insulin sensitivity the krill/salmon oil group had a 27% lower insulin sensitivity (P < 0.01).

They don't mention it in the abstract, but from the free full text, other negative metabolic changes in the KS condition relative to the canola oil condition that were close to statistically significant included: Increased fasting glucose (P = 0.092), increased carotid artery thickness (P = 0.068), increased total (P = 0.11) and LDL (P = 0.20) cholesterol, and Apolipoprotein B (P = 0.053).

When the researchers looked at how metabolic measures changed between the start and the end of the 8-week KS-oil period (rather than comparing the KS-oil condition to the canola oil condition), these negative metabolic changes with the KS-oil supplement became even more dramatic:

Although there was no significant change in insulin sensitivity from baseline with the control oil (P = 0.23), participants experienced an 18% decrease in the Matsuda index (P = 0.002) while taking KS oil (Supplemental Table 1). The deterioration in insulin sensitivity after KS-oil supplementation was corroborated by the HOMA-IR that increased by 0.39 (P = 0.016) and fasting insulin that increased by 1.39 mU/L (P = 0.048; Supplemental Table 1). KS-oil supplementation was also associated with increases in carotid artery intimamedia thickness (+39 mm; P = 0.001) as well as apolipoprotein B (+8.02 mg/dL; P = 0.009), total cholesterol (+0.31 mmol/L; P = 0.0004), LDL cholesterol (+0.27 mmol/L; P = 0.001), and HDL cholesterol (+0.08 mmol/L; P = 0.034) concentrations (Supplemental Table 1).

That's some pretty significant adverse results from only 8-weeks of supplementing with (mostly) krill oil. The authors agree:

Thus, our findings suggest that krill- and/or salmon-oil supplementation may increase risk of developing type 2 diabetes and cardiovascular disease.

Surprisingly (to me) the authors seems to be at a loss to explain the effect. They rule out or heavily discount several possible explanations for these adverse metabolic differences, including:

A positive effects of the canola oil on these parameters, since subjects got a lot worse in the before/after comparison of KS-oil, independent of the canola oil control condition.
The DHA/EPA, which have widely been shown to either improve or at least not worsen metabolic health at these doses (400mg/d total Omega-3s).
The salmon oil in the blend - since it was only a small fraction of the total amount, and prior fish-oil trials have shown no similar adverse effects on metabolic health.
The carotenoid astaxanthin, which is abundant in krill oil, since astaxanthin if anything has been shown to improve insulin sensitivity in other studies, and is also abundant in salmon / fish oil.

The authors then skip right past what I believe to be the obvious "smoking gun" (more on that below), to conclude vaguely:

We speculate that there are compounds present in krill oil that impair insulin sensitivity, and they are either not in fish or, if present in fish, are mostly excluded during oil extraction. The identification of these compounds could lead to a better understanding of the metabolic effects of marine oils that are not sourced from fish and possibly to processes that would exclude them from supplements.

What did they miss? It's staring them in the face, in fact they trip over it:

Unlike fish oil in which fatty acids are predominantly incorporated into triglycerides, in krill oil, fatty acids are largely present as phospholipids. This difference is also unlikely to explain the observed reduction in insulin sensitivity. The KS oil used in this study was 42% phospholipids by weight, with the vast majority (76%) in the form of phosphatidylcholine.

The health effects of dietary phospholipids are not well understood, but limited evidence suggested that a higher phosphatidylcholine fraction of membrane phospholipid is associated with greater insulin sensitivity (51). Thus, if supplementation with krill oil leads to a greater cell membrane phosphatidylcholine fraction, a reduction in insulin sensitivity would not be expected.

Under what rock have these guys been hiding?

As we discussed extensively here, too much phosphatidylcholine (PC) looks like bad news. It feeds TMAO producing bacteria in the gut, leading to exactly the kind of arterial narrowing and increased CVD risk (PMID 23614584 & 27287696) the authors observed with krill oil supplements, via the pathway shown below:

It really surprises me the authors didn't pick up on this connection, nor did the reviewers, given that it was in the American Journal of Clinical Nutrition, a very well-respected journal. Their study [1] was published last year, and the evidence for the phosphatidylcholine → TMAO → CVD link has been around at least since PMID 23614584 was published in 2013 in the prestigious New England Journal of Medicine. Weird...

So how much PC were these men getting from the krill oil? A heck of a lot, it turns out. They were taking 5g per day of the krill/salmon mixture. Multiplying out all the numbers we get 5.0 x 0.88 x 0.42 x 0.76 = 1.4g of phosphatidylcholine per day.

That is nearly 3x the RDI for choline, and the equivalent of eating per day:

4 servings (3oz) of steak,
18 servings (3oz) of salmon,
3.75 pounds of shrimp, or
11 large eggs,

So it's little wonder these men were turned into walking heart attack factories with all the PC they were eating...

Pretty scary result.

Long ago I used to supplement with krill oil for my omega-3s, but thankfully only at ~1/20th the dose these guys were getting. I've long since switched to algae-based DHA/EPA to meet what I consider to be a minimum long-chain omega-3 requirement. Thanksfully algal oil doesn't contain PC/choline.

This seems like pretty strong evidence in favor of the theory that Michael seems to pretty much dismiss (or heavily discount) on the other thread, namely that too much dietary phosphatidylcholine can lead to an increased risk of CVD by feeding bacteria in the gut that produce detrimental TMAO.

The other obvious takeaway message: It is probably best to avoid krill oil...

--Dean

P.S. Here is a great resource on choline health effects and dietary needs.

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[1] Am J Clin Nutr. 2015 Jul;102(1):49-57. doi: 10.3945/ajcn.114.103028. Epub 2015

May 27.

Supplementation with a blend of krill and salmon oil is associated with increased

metabolic risk in overweight men.

Albert BB(1), Derraik JG(1), Brennan CM(1), Biggs JB(1), Garg ML(2),

Cameron-Smith D(1), Hofman PL(1), Cutfield WS(3).

Author information:

(1)Liggins Institute, University of Auckland, Auckland, New Zealand; and.

(2)Nutraceuticals Research Group, University of Newcastle, Callaghan, Australia.

(3)Liggins Institute, University of Auckland, Auckland, New Zealand; and

w.cutfield@auckland.ac.nz.

BACKGROUND: Krill is an increasingly popular source of marine n-3 (ω-3) PUFA that

is seen as a premium product. However, to our knowledge, the effect of krill-oil

supplementation on insulin sensitivity in humans has not been reported.

OBJECTIVE: We assessed whether supplementation with a blend of krill and salmon

(KS) oil [which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid

(DHA)] affects insulin sensitivity in overweight men.

DESIGN: The design was a randomized, double-blind, controlled crossover trial. A

total of 47 men with a mean ± SD age of 46.5 ± 5.1 y, who were overweight [body

mass index (in kg/m(2)) from 25 to 30] but otherwise healthy, received 5 1-g

capsules of KS oil or a control (canola oil) for 8 wk and crossed over to another

treatment after an 8-wk washout period. The primary outcome was insulin

sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance

test. Secondary outcomes included lipid profiles, inflammatory markers, 24-h

ambulatory blood pressure, and carotid artery intimamedia thickness.

RESULTS: Unexpectedly, insulin sensitivity (per the Matsuda index) was 14% lower

with the KS oil than with the control oil (P = 0.049). A mediation analysis

showed that, after controlling for the likely positive effects of blood EPA and

DHA (i.e., the omega-3 index), the reduction in insulin sensitivity after KS-oil

supplementation was more marked [27% lower than with the control oil (P =

0.009)].

CONCLUSIONS: Supplementation with a blend of KS oil is associated with decreased

insulin sensitivity. Thus, krill-oil supplementation in overweight adults could

exacerbate risk of diabetes and cardiovascular disease. This trial was

prospectively registered at the Australian New Zealand Clinical Trials Registry

as ACTRN12611000602921.

DOI: 10.3945/ajcn.114.103028

PMID: 26016867

Saul · June 30, 2016

Thanks, Mike and Dean.

I remember, Conrad Roland, on the old Lists, who lives in Hawaii, supplemented with krill oil to get his omega 3's. He had thought that krill oil was better than fish oil, because (he argued) it was, he reasoned, less prone to oxidative damage.

I'm nearly sure that Conrad is not reading the Forums -- I just sent him an an email, including the URL of this thread.

:(xyz

-- Saul

Edited June 30, 2016 by Saul

mikeccolella · July 1, 2016

Thanks Dean your a wonder!

Sibiriak · May 30, 2017

Dean Pomerleau: So how much PC were these men getting from the krill oil? A heck of a lot, it turns out. They were taking 5g per day of the krill/salmon mixture. Multiplying out all the numbers we get 5.0 x 0.88 x 0.42 x 0.76 = 1.4g of phosphatidylcholine per day.

That is nearly 3x the RDI for choline,

That doesn't appear to be correct.

Phosphatidylcholine contains approximately 13% choline.

http://lpi.oregonstate.edu/mic/other-nutrients/choline#food-sources

http://www.longecity.org/forum/topic/54272-another-day-another-pill-2012-supplement-regimen/

1.4g phosphatidylcholine x .13 = 182mg choline, about a third of the RDI.

The RDI for choline is 550mg [Previously, Adequate Intake (AI) 550mg--adult males/ 425mg --adult females].

http://www.prnewswire.com/news-releases/choline-joins-the-nutrition-facts-label-300274009.html

https://www.ncbi.nlm.nih.gov/books/NBK114308/

https://www.crsociety.org/topic/11136-nutrition-and-supplementation-for-vegetarians/#_edn91

Edited May 30, 2017 by Sibiriak