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!
Matt Colflesh says
“For those who believe, no proof is necessary. For those who don’t believe, no proof is possible.”
-Stuart Chase (writer and economist, b.1888)
Robb Wolf says
Mike Molloy says
Love the Cell paper!
I was pretty shocked that despite GPR120 being expressed on both macrophages and adipose tissue, so much of the benefit from the n-3 supplementation could be attributed to alteration of the macrophages. Of course there are direct effects upon the adipose tissue but so much of the disease can be attributed to the macs getting feisty! Very interesting stuff
Robb Wolf says
Yea, they go looking for a fight and get other cells stirred up.
I tried to follow the post as closely as a I could, but at some point my eyes glossed over. I want to make sure I’m getting the message, that we want to continue to take large amounts of fish oil right? I think of jumping the shark as a bad thing, so I was confused by the title of the article.
Robb Wolf says
You are likely fine at the .25g/10lbs bw level. Sorry i lost ya, the point of the article was that high doses are appropriate and normal for the right circumstance.
Chris Robbins says
I’d like to add a recent study that I linked to through my blog, Paleoish.com, about the importance of a taurine & magnesium rich diet in reducing heart disease & stroke risk that I think should get more attention. Some of my favorite excerpts:
“Australian Aboriginals living at the coastal area in Victoria were supposed to eat T- and M-rich bush and sea foods and be free from CVD 200 years ago, but they presently have nearly the highest CVD risks indicating that T- and/or M-containing seafood, vegetables, fruits, nuts, milk, etc, similar to prehistoric hunters’ and gatherers’ food should be good for CVD prevention.”
“Our experiments to feed SHRSP on high or low fish protein diets with or without 1 % salt in drinking water first demonstrated that fish protein rich in T attenuated salt-induced severe hypertension and decreased stroke incidence from 80% down to 10% [4,15]. High fish protein diet with low salt in drinking water was proven to be most effective to reduce stroke down to 0%. We further investigated the effects of several amino acids contained in fish protein in SHRSP and confirmed that T is effective for reducing blood pressure (BP) in SHRSP.”
“As hunters and food gatherers, Aboriginals, according to the 2-week food intake analysis report, were supposed to live by taking their energy, for example, 34% from complex carbohydrates, 13% from fat and 53% from protein . Although we do not know exactly what they ate, we tentatively suppose, for example, they ate 400 g of yam, 300 g of frogs, 5 g of almonds, 140 g of bream, 200 g of clams, 300 g of snails. These foods contain about 100 g of carbohydrates, 15 g of fat and 170 g of protein and correspond roughly to 1300 kcal/day. The daily intake of T and M from these foods is about 3200 mg and 640 mg, respectively, both being far higher than the average of CARDIAC populations in the world.”
You can read the full text here:
Robb Wolf says
Aaron Blaisdell says
Wow, awesome stuff. Your master plan to guide the research enterprise looks a lot like what my colleagues and I who are starting the Ancestral Health Society and its annual symposium envision. It looks like we’ll also need a scientific/medical journal centered on the evolutionary framework for investigating human health. That may have to be moved up to the front burner pretty soon.
President, Ancestral Health Society
Robb Wolf says
Let’s talk. If you guys have more traction no sense in us re-inventing the wheel.
Aaron Blaisdell says
Sure thing, Robb. The University of California has an eScholarship branch with hosting open-source journals as one of its missions: (current journals can be viewed here: http://escholarship.org/uc/search?smode=browse;browse-journal=yes).
This machinery could make it easy to get a journal up and running. We would just need an Editorial board and staff interested in making the thing run. I’ve toyed with the idea of starting a journal where people could publish their critical analysis of health research reports, such as the recent spate of China Study critiques, but it would be great to get something grander in operation which would include publishing new data from an evolutionary/ancestral/paleo fitness and health perspective.
I’m happy to discuss these ideas.
Robb Wolf says
This would be amazing!! There is also some good stuff happening at the Journal of Nutrition and Metabolism. I will email you right now so we can chat more.
I’m 290lbs, 30 year old, doing lowcarb/paleo for almost 9 months. Blood sugars down from highs of 300s in Jan. to <100 all the time. I've been taking 3-5 fish oil pills morning and night since I started this way of life. I found your fish oil calculator last week and am working my way up to the 50 pills/day it says for a .5 factor. When I check my blood sugar (mostly out of curiosity now) I notice how much thinner my blood is. I'm taking around 40 pills (1000mg w/ 300mg of n-3) daily in 3 to 4 doses spaced out at breakfast, lunch, supper, and bedtime. My parents are worried about the blood thinning and I'm curious about the safety of taking that much (but I'm guessing it doesn't effect clotting as much as just general thinning). I'm thinking it is ok but wondering if I should titrate up to the high dose and if I should continue to space the dose out or take it all at once or only take them with a meal (if I I.F. at lunch or something).
Robb Wolf says
you may have turned the corner on things and may not need that much. .5g/10lb bw is likely plenty. You could have your doc run a co-ag panel.
I’ve been supplementing with fish oil (~9g @ 160lbs bw) for about 3 months while eating Paleo (no grassfed, omega3 eggs or wild caught fish. I’m working on that.)
Could I drop down to ~4.5g without worrying about my o-3/o-6 ratios going out of balance if eating non-grassfed beef, omega3 eggs etc.?
You mentioned in the podcast a while ago that you should be fine after 2-4 months (depending on how out of whack your levels are to begin with) dropping down to a lower dose.
Sorry if you’ve covered this elsewhere, still going through your forum-post compilations.
Robb Wolf says
Man, it’s hard to get your book here in Europe. Been on the “alert”-list since it came out. Then I read by e-mail today and I had gotten a message on saturday that it was finally available for order. Well, too late, sold out!
Very interesting stuff. I was surprised that linoleic acid(18:2 n-6) was inversely related to diabetes. I thought it might be associated to increased risk.
Thanks for all that you do! I am a healthy 26 year old female. I started eating Paleo and taking fish oil about 2 months ago and noticed an increase in acne. After listening to the podcast, I tried some borage oil as I assume I am one of those women who have a hard time breaking down omega 3. The borage oil really seems to help with the acne. So, my question is: If I eat primarily grassfed meat, do I continue to take small dosage of fish oil and borage oil? At what point, if any, should I stop taking the borage oil or fish oil? Thanks!
Robb Wolf says
It’s not an issue of breaking down the fish oil, you like just do not need it relative to the borage oil. I’d ditch the fish oil, eat GF meat and play with the borage dose to see what the minimum is to keep you acne free.
I just saw this retweeted by Martin Berkhan, and I wanted your input. I know Martin’s not a big fan of paleo, and this is a rat study, but I still find it moderately concerning.
Robb Wolf says
I’d need to look at that more closely, but it just reinforces “get it from your food.”
Ideal to get it from your food, but your calculator says to
start that I should be taking 18.5 grams a day, which just isn’t
possible without supplement. I haven’t been able to find any more
information about this study, or anywhere that gives the actual
data from the tests that they did or how they were performed. Have
you been able to find any more information on this? Or do you have
any more of a take on it since initially reading it?
Robb Wolf says
If you are not sick you may nit nee much at all!
Deanne from SW Washington says
Bought your book on the recommended of Julianne’s Paleo & Zone Nutrition Blog who introduced me to the idea of Paleo. My husband and I have been on this diet about two weeks. We are in our early 50’s and obese. I have noticed in two weeks several benefits and we are extremely encouraged as to what else this diet improves.
For me female, Rosacea gone, eczema gone, swelling in ankles almost gone and continues to get better. Both of us have lost a lot of swelling or inflammation all over. Skin less taunt from all the swelling. Pain all over has been reduced. Stiffness in hands less. My husband has stopped using prescription nasal spray for allergies and I am about to. We may also stop suing generic zyrtec too at this rate. Energy levels up significantly.Our pain all over has been reduced.
We are not losing weight but clearly our shapes are toning up and we aren’t doing much exercise but on the treadmill 3 x week for 30 minutes. We are slowly remodeling and we are relatively active. We take gummy multivitamins since my stomach was more easily upset. But my stomach is doing much better so I may switch to regular vitamins minus the sugar part. Any recommendations? Make cost an important consideration.
We also take 4Kg of Vitamin D, zyrtec, and 1Kg of flaxseed oil. I also take 200mg of ibuprofren for swelling and pain which is a joke for Fibromyalgia but my stomach can’t take too much of the ibuprofren but four of them actually helps with the pain. My father took too much of that two decades, I think 1800mg, ago as prescribed and ended up with aneurysm so I watch that stuff.
You recommended high doses of fish oil and if I go by what you say 1 gram to every 10 lbs of body weight I would be taking 27 grams a day! My husband about 31 grams! That is a lot of fish oil. That would run us maybe 160ish dollars a month in fish oil which is not possible on teachers salary. I also have heard there is some controversy about taking so much fish oil. I base this on 4oz bottles of fish oil at 42.00 which contains 24 teaspoons. Some say the grams per teaspoon varies from 1.6 to 5 grams. Either way it adds up in a hurry. Got any better ideas on how to do this fish oil thing cheaper?
I just picked up the Natural Calm yesterday for Fibromyalgia and I tried it and it was ok. 1/2 t. before bedtime with hot water and maybe slowly ramp it up?
Because we can see the benefits so quickly we are all the more encouraged by following your advise and my god if you can help me reduce the pain for Fibromyalgia that would be huge along with weight loss. I am giving up on fruit to cut down carbs for Fibromayalgia.
We are not training for anything at this point but want to lose weight and reduce pain in a practical way. Is there some easy rules to follow for portion size for older obese folks like us?
Thanks for writing this book!
Robb Wolf says
Just eat slowly, satiety will be your guide. That fish oil recommendation is only for a brief time to turn thing’s around but it sounds like you guys are doing great. Shoot for that .25g/10lbs BW and let me know how you are doing.
Deanne from SW Washington says
We are trying to know what satiety is for us now after decades of eating till we are full. We eat slower for sure but after watching Dr. Lugwig’s The Bitter Truth video about sweeteners it is no wonder we are eating so much and have no idea when to stop. Fructose is in everything and it prevents your brain from knowing what full is. If sweeteners can fry a pancreas and turn off normal full triggers for eating what else has it done and is it also permanent? Is there any science that supports that your body is able to know satiety soon enough after years of chemical doping by fructose etc? We have tried to eliminate sweeteners from diet but we have learned to not assume it is not in everything when shopping now. Eye opener. Still trying to get out all forms of night shade plants in spices since no more salt or soy sauce.
That leads me to another question about fructose…Dr. Lustig explained much better than I about how fructose stores differently in the body than other things by storing fats or whatever in muscles. That got me thinking about my Fibromyalgia and how my muscles feel fried, tired and sore from doing nearly nothing and also when I do stuff. Could fructose have affected my muscle’s ability to regulate pain? Did it burn out the nerves or something? Did it cause it to misfire or to send out wrong signals? Does it do it differently to women vs men?
I went to seminar at Kaiser Permenente for Fibromyalgia seminar about 3 yrs ago. Thankfully I have another health care provider but at the time I was stuck and all they did for Fibromyalgia patients is send us to seminar and track us as pain management. The seminar comprised of bored doc who handed out bibliography and physical therapist telling us we will not chase down all your aches and pains. Wow the women were upset at that presentation and rightfully so. One woman, out of desparation and frustration, burted out two commonalities she saw within the large conference room filled with women. One we were all women for the most part and we were all over weight. She asked what does that mean?
Do women process fructose differently than men?
Nowhere in the bibliographies did they even mention about Paleo or diet really and I for one have had a decrease in pain without all the side affects from drugs they like to pass out. I am moderately mad now. Once you feel better and you know better and you wonder where the hell is the medical community on this? My doc told me to use capasasin to deaden the pain vs taking pills. I wonder if I absorbed more nightshade that way making it worse! I wouldn’t surprise me if they bleed Fibromyalgia patients to get the bad blood out. It really hasn’t advanced much beyond that.
What was scary was women there started speaking up and recommending drugs to take to each other at the seminar, which were hard core like stage four cancer end of life pain remediation as a viable option! My jaw dropped along with my husband’s when we heard this and I am sure Kaiser was prescribing them! I looked at my husband and we both looked at each other and we were shocked that there is no way these women could possible function at work or anything sedated with these drugs. When some women spoke up and angry others went to comfort them. This is a female issue no funding and women really know how to lay down and die really well for medical community so as not to upset the apple cart. The worse ones with this condition were the ones to comfort the other who expected more. Sad really.
Since Italian researcher just this year discovered/proved Celiac can be acquired as an adult not just at birth he once again turns our assumptions upside down like the fact 1 in 100 in the U.S. has this autoimmune condition. The tip of the iceberg is what we are seeing. I know WSU is researching new gluten free wheat and big agri sees the writing on the wall and is trying to buy time and new ideas to keep the grain gravy train going. I feel like with this diet my body is getting better and able to spend some time repairing rather than fighting off foods that are foreign and playing out in so many ailments. I also think that Fibromyalgia is not in my head or my sleep but rather affects of my environment and really very possibly food. Has there been any really good science that proves one way or the other on food as agent that causes Fibromyalgia?
I see at Stanford they do these trials but they seem lame in a way to me when they say they screen for inflammation but inflammation of what and how much and ..you get the idea. But I guess that doesn’t bring in money for the university to sucker punch big business food with research findings that contradict their food advertising. So bravo to you and Dr. Cordain to step up and say the king has no clothes/grains, legumes,etc are not healthy and kudos for those who support your efforts.
Do you know of an universities who are really researching this well about Fibromyalgia and if there is food connection?
I have taken the 1/2 t. of magnesium with water before bedtime but some nights it doesn’t settle well and keeps me awake.
I really enjoyed your book. It has been helpful in convincing people close to be to cut the final cords. My friend is now fully paleo and has started consuming high doses of fish oil to combat inflamation. He was/is stuck at 300 pounds not sleeping and fairly miserable. This week he has cut the final cheese and nuts from his diet. Now he is focusing on getting more sleep. How soon should he start seeing positive results from the fish oil and other diet changes? We currently lift twice a week and I’m working on getting him to walk more. He is off all his diabetes medicine and blood sugars range from 100-120 in the mornings. I’m looking for what to expect to help keep him on track. Anything else you can add would be helpful.
I know in your book you recommend quite a few excellent sources of omega-3 foods that have a healthy balance of Omega-3 to Omega-6. This seems to be a smaller list than the items I have stumbled across / have been recommended to me for Omega-3.
Now I’m curious, do some items such as flax seed meal or walnuts, not have the appropriate mixture of fats? What are some commonly popular Omega-3 sources that one should avoid? Where can I find statistics on various foods in terms of Omega-3 to Omega-6 ratios?
I’m doing the big initial dosing of fish oil (which is not much fun…) and stumbled across a product called “Vectomega”. I’m not literate enough in nutrition science to know if it is “the next great thing”, ridiculous or something in between. The claim is that the bioavailability of the EPA and DHA in Vectomega is 40x greater than in fish oil. The company website is http://www.vectomega.com I’d be grateful for your opinions. Thanks!
Robb Wolf says
CRAP. Nothing improves absorption that much.
I’m another “fat, 50’s, fair, and female” (so they removed my gall bladder ten years ago) who’d be taking 30 “Super Omega 3” (LEF.org capsules) a day. (!) Those have 700 mg of EPA and 500 mg of DHA (which would mean — or wouldn’t it? — that I actually need MORE capsules to reach the 30g EPA/DHA?). I’m half-way through your excellent book. Is krill oil a better source of the EPA and DHA — at least the capsules are smaller for the same amount of EPA/DHA.
I’m dreading, but willing to take, 30 capsules a day for two months (just swallowed five of the darned ‘horse pills’…) but if krill oil will suffice in place, it would be WAY easier to (quite literally) swallow!
Thanks Robb for all you do!
Robb Wolf says
Krill oil is totally fine. Remember, just a 3-4 weeks to get things turned around.
Just starting on the paleo, but generally healthy. My Vitamin D level is at low 21. Will be taking Vit D 5000 iu serum (from lanolin). Are there any issues with vit d & fish oil together? Would it be safe to take the fish oil at .75 factor? Suspect hubby has gaps or celiac or a digestive auto immune issue. Could you give us dosage recommendations for the fish oil along with the vit d 5000 iu? Hubby will also take same dosage for Vit D. Thanks so much!
Amy Wike says
Natural, organic fish oil pills are great for you, in moderation.