Unless you have been under a rock for the past few years you have likely caught wind of this stuff called omega-3 fats (n-3) and are savvy as to their utility in reversing or preventing a metric-ton of health problems. For some folks this knowledge is literally, easy to swallow (take some fish oil, live better) for others I get a little push back (why do I have to take all these pills?). As many of you likely know n-3 fat’s have been largely displaced from our diets. Our ancestral foraging life-way provided approximately 1/1 to 1/2, n-3/n-6 fats, modern diets look more along the lines of 1/10 to 1/20 because our meat and dairy is grain and soy fed while traditional sources of fat have given way to high n-6 fat sources like corn, soy, sunflower and similar seed oils. This is “No Bueno” as the n-6 family of fats influence (generally) pro-inflammatory products from the prostaglandin, cytokine, leukotriene and other chemical messenger families. We usually throw these products in the broad category “eicasanoids” and some of the best, earliest information on eicasanoids came from Barry Sears/Zone scene before he Jumped the Shark and told us Molecularly Baked Bagels were the Beezz-Neez.
WELL! As with everything, the story get’s more complex and more interesting. A recent paper (a mouse model, but pretty interesting none the less) indicates that an entirely novel inflammatory pathway, unrelated to the eicasanoid family of chemical messengers, appears to be at ground zero in the story of inflammation and insulin resistance. N-3 fats, specifically EPA and DHA (sorry vegans, ALA does not count here!) appear to have a specific receptor in a variety of tissues, but important to this paper, adipose (fat) tissues. This receptor, GRP-120, lies at the heart of the insulin resistance that results from increasing levels of systemic inflammation. Here is a piece of the introduction from this paper:
“Chronic activation of inﬂammatory pathways plays an important role in the pathogenesis of insulin resistance and the macro- phage/adipocyte nexus provides a key mechanism underlying the common disease states of decreased insulin sensitivity (Schenk et al., 2008). This involves migration of monocytes/ macrophages to adipose tissue (including intramuscular fat depots) and liver with subsequent activation of macrophage proinﬂammatory pathways and cytokine secretion. Through paracrine effects, these events promote inﬂammation and decreased insulin sensitivity in nearby insulin target cells (Shoelson et al., 2007; Schenk et al., 2008).”
I emphasized some of the middle material talking about the migration of monocytes and macrophages (immune cells) to adipose tissue because I want you to contemplate this picture:
We have a huge assortment of immune cells hanging around our bodies and they are all pretty handy for “staying alive” type stuff. These immune cells are our vigilant defenders, cruising the town, keeping an eye on things. They are not generally bullies, but if they get a little agitated they can start picking a fight with things they should not. If our immune system gets really agitated it can pick a fight with everything and in the process do exactly the opposite of what it is charged to do: keep us alive. What is important to note from the piece above is that immune cells INFILTRATE adipose tissue (think breaching a door and storming a building) and they set up shop in places they do not really belong. All because of excessive inflammation. Inflammatory signals sent by the adipocytes (fat cells) act like blowing a police whistle, and the immune defenders come a running. The only problem is they do not really have anything to fight…but they are agitated and release chemical messengers that make the inflammation worse.
Via some slick molecular biology and collaborative tests, the authors of the aforementioned paper show that n-3’s are critical in their interaction with GRP-120 not only for decreased inflammatory effects, but also for insulin sensitivity. It would appear that inadequate n-3’–> decreased GRP-120 expression–>increased inflammation+decreased insulin sensitivity. Net result? A ton of mierda.
Here is another interesting snippet from that paper:
“A separate group of WT mice were treated with the insulin sensitizing thiazolidinedione Rosiglitazone, and the effects of u-3 FAs were equal to or greater (HGP suppression) than the effects of this clinically used insulin sensitizing drug.”
In the above WT refers to “wild type” which was one of the genetic controls in this study and HGP refers to “hepatic glucose production”. What it means is n-3 are as good or better than pharmaceuticals at reversing two of the main features of Type 2 diabetes: insulin resistance and abnormal hepatic (liver) glucose production. The liver does this because it thinks we are starving…this is one of the ironic elements of the progression of insulin resistance and a topic I explored at nauseating length in the Paleo Solution. The irony cannot be thicker here in that we have a host of pharmaceuticals being used to treat insulin resistance while inexpensive fish oil will address these problems better and with far fewer side effects. So, this is some pretty interesting stuff as it explains another mechanistic piece of n-3’s powerful anti-inflammatory effects but it does not address the “how much fish oil should I take?” question. To properly address this let’s consider how much n-3/n-6’s folks are running around with.
How much fat ya got?
This next paper is kinda cool in that it is virtually identical to the work I did previously: analyzing the fatty acid fractions in red blood cells (RBC’s). Folks let me tell you, extracting, esterifying and analyzing RBC membrane fats is a PARTY! What we see from this work is a significant skewing of n-6 relative to n-3 in the development of insulin resistant diabetics. We also see a “paradoxical” finding that dairy derived short chain saturated fats are protective against insulin resistance. SHOCKING! If you think about it, these folks have literally POUNDS (kilos?) of pro-inflammatory signal coming from those n-6 fats.
If we want to turn the Titanic away from the iceberg, we need to work fast. Reduce insulin secretion, reverse liver pathology (from excessive carbs, n-6, and grain based lectins) and restore tissue insulin sensitivity (get some exercise, go to bed and sleep). High dose fish oil can literally be a lifesaver in this situation and from a purely mechanistic level considering the actions of GRP-120, we can understand why. The relative lack of n-3 fats in our modern diet allows for a feed-forward progression of inflammation and insulin resistance. Folks who are sick (insulin resistant, inflamed, suffering autoimmunity) seem to benefit greatly from n-3 intake in the 1.0g((EPA+DHA)/10lbs bodyweight/day. For a 200lb person that may mean as much as 20g of EPA/DHA per day, EGADS! For some people this may represent a huge whack of fish oil, but the n-3’s reverse inflammation and the associated insulin resistance. Folks look, feel and perform better. Biomarkers of health improve. Eventually folks can titrate down to ~.25g of n-3/10lbs BW which is really no big deal.
Let’s take a look at a section from a recent paper by Prof. Cordain and crew:
“We found (range of medians in en%) intakes of moderate-to-high protein (25 – 29), moderate-to-high fat (30 – 39) and moderate carbohydrates (39 – 40). The fatty acid composition was SFA (11·4 – 12·0), MUFA (5·6 – 18·5) and PUFA (8·6 – 15·2). The latter was high in a-linolenic acid (ALA) (3·7 – 4·7 en%), low in LA (2·3 – 3·6 en%), and high in long-chain PUFA (LCP; 4·75 – 25·8 g/d), LCP n-3 (2·26 – 17·0 g/d), LCP n-6 (2·54 – 8·84 g/d), ALA/LA ratio (1·12 – 1·64 g/g) and LCP n-3/LCP n-6 ratio (0·84 – 1·92 g/g). Consistent with the wide range of employed variables, nutrient intakes showed wide ranges. We conclude that compared with Western diets, Paleolithic diets contained consistently higher protein and LCP, and lower LA.”
This is a largely theoretical paper attempting to reconstruct the ancestral diet of Eastern Africa but some interesting tidbits emerge: EPA/DHA intake was likely in the range of 3-17g/day, n-3/n-6 ratios were approximately 1-2. Holy cats! That’s what we see as being healthful today!
Cant We just be Moderate?
An interesting effect of the book’s success has been placing the notion of Evolutionary Biology squarely in front of everyone from body-builders to 21 year old world saving Vegans to militant registered dieticians. Now, simply asking these folks to read the literature (topic of an upcoming post) seems to largely fail, but the contents of this post points in a direction all biomedical research needs to go IMO:
1-Let’s look to our evolutionary past for a theoretical framework from which to ask questions.
2-Let’s consider available epidemiology (STARTING with hunter gatherer populations!) for some corroroborative information that helps us formulate proposed mechanisms of action based on our evolutionary observations.
3-Animal models studying the proposed mechanisms.
4-Human trials studying the proposed mechanisms. Where appropriate let’s just skip #3 as animal metabolism is (drum-roll) different than human and thus only suggestive, not definitive.
5-Start looking for genome wide variations people are different…these findings may apply differently to different populations depending upon how conserved the particular metabolic engines we are looking at.
Michael Pollan has made the point that a reductionist approach to nutrition leads to “nutritionism” and a loss of “holistic” eating. I’ll buy that but a lack of reductionism would also not uncover things like lectin intolerance and the discovery of the GRP-120 protein. We need an evolutionary framework from which to ask questions, we need reductionist biomedical research to ferret out the details. Well, if we really want to understand what is going on. If that is not on your agenda just adopt a stance of “moderation”, that always works!