Linoleic Acid, Fat Rats in Labs, and Fat Humans
Scientists generally have no idea what they are using in their experiments.
Stephen Guyenet once posted:
“...High fat diets, particularly in combination with refined starches and sugars, were among the most effective. The composition of these diets has been refined since then, and modern “purified” high-fat diets reliably induce obesity in susceptible strains of rodents. The most commonly used diet is Research Diets D12492, which is 60% fat by calories, and composed mostly of lard, soybean oil, casein, maltodextrin, sucrose and cellulose (7). It tastes kind of like raw cookie dough, and the rats are crazy about it.”
Turns out a whole big chunk of science has been drawing faulty conclusions:
“...I got an email today from Dr. Matthew Ricci, the Vice-President and Research Director of Research Diets, the company that produces the infamous 60% fat, lard-based rodent diet D12492. I’ve written about this diet before. The company had previously been using the USDA database to determine the diet’s fatty acid profile, but recently had it directly analyzed, knowing that the fatty acid profile of lard can vary according to what the pigs are fed.
“It turns out that the diet obtains 32% of its fat from PUFA instead of the previously reported 17%. The ratio of omega-6 linoleic acid to omega-3 linolenic acid had been previously reported as 7.8 but is actually 14....”
Whoops. Chris Masterjohn compliments Research Diets on their transparency, which compliment they are due. However, Research Diets made a big mistake. To paraphrase a line from Animal House, “They f---ed up, they trusted the Federal Government.” Obviously the USDA is not a reliable source of nutritional information.
The following is from one of several emails I sent to Stephan Guyenet in April 2010, shortly after I fixed my diet (and contributed $100 to support his blogging efforts):
“One more update. I’ve been going through your site and it occurred to me that some of the other effects I’ve seen might be of interest.
“We have a candy bowl in the office. Once of the first things I noticed after dropping n-6 from my diet was that I was no longer craving starch and sugar. I haven’t hit the candy bowl in 3+ weeks. Didn’t feel a need to. My wife also noticed after not eating n-6 that she was no longer craving starch (and this has been a big problem for her).
“I didn’t start craving fat for 3-4 days after making the change, and had almost no starch or sugar in the interim...
“I know you stress cutting starch[*] more than n-6 in your thinking. I didn’t want to change too many variables at once in my experiment, but since I don’t eat processed starch or sugar, I figured removing the n-6 was the more significant change to make.
“It makes me wonder if there might be a mechanism linking the two...”
This sounds a lot like what happens to the rats. I think Stephan may want to reconsider this post:
“As my knowledge of obesity and metabolism has expanded, I feel the evidence behind the hypothesis that seed oils (corn, soybean, etc.) promote obesity due to their linoleic acid (omega-6 fat) content has largely collapsed. “
I was very surprised when he posted it, as his previous position coincided perfectly with my experience as stated above. It also turns out that the research he now quotes in support of the problematic food reward hypothesis also supports the position he’s abandoned, given this updated information on the composition of the diets he cites.
Stephan may have reconsidered his position on seed oils, but I haven’t. I still avoid them like the plague, as they had a clear effect on me once I stopped eating them.
If you want to “reliably” induce obesity in humans or rats, feed them high amounts of linoleic acid**.
* Stephan corrected me about his thinking on starch he’s basically OK with it. And I think he’s likely correct, so long as you’re not eating large amounts of linoleic acid.
** Your results may vary. :)
P.S. Chris Masterjohn posted a follow-up at the Weston A. Price Foundation website: Good Lard, Bad Lard.
One other thought: my sure-fire test to find out what chips are fried in is to start eating them. With chips fried in olive oil or animal fat, I eat a few, and then move on. With chips that are fried in seed oils, you eat the quantity presented to you, and then you want more. This has been reliable enough that I’ve been able to detect when the staff at a restaurant gives me bad information about the constitution of the chips that are served.
P.P.S. “Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity“
Original post: November 19, 2011
I've mentioned this before, but any reader of Hyperlipid knows to always check the ingredients of the lab chow first.
Be especially cynical about lard. They started adulterating lard with cottonseed oil in the 1800s.
"If you want to “reliably” induce obesity in humans or rats, feed them high amounts of linoleic acid."
Actually, according to Norwegian animal science researchers, high intake of linoleic acid will reliably displace arachidonic acid molecules from their positions in cell membranes. Excerpt: "Because AA competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation. Thus, the best strategy for dampening prostanoid overproduction in disease situations would be to reduce the intake of AA, or reduce the intake of AA at the same time as the total intake of competing fatty acids (including oleic acid) is enhanced, rather than enhancing intakes of EPA and DHA only. Enhancement of membrane concentrations of EPA and DHA will not be as efficient as a similar decrease in the AA concentration for avoiding prostanoid overproduction." https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-9-37
Prostanoid overproduction does not affect feeding behavior. However, endocannabinoid overproduction does. Excerpt: "Experimental and clinical intervention studies suggest that omega-6 and omega-3 fatty acids have opposing physiological and metabolic properties and elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, systemic inflammation and an increase in the tone of the endocannabinoid system. Overweight and obese individuals have higher levels of the arachidonic acid (AA) derived endocannabinoid N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) and an altered pattern of receptor expression. Since endocannabinoids are products of dietary fats, modification of the omega-6 and omega-3 fatty acid intake modulates the endocannabinoids, with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) displacing AA from cell membranes, reducing AEA and 2-AG production, resulting in decrease in appetite and food intake leading to weight loss." https://www.ocl-journal.org/articles/ocl/full_html/2020/01/ocl190046s/ocl190046s.html
Eicosanoid and endocannabinoid production increases and decreases in parallel in response to proportionate changes in fatty omega-6s and 3s. Note, however, that fat-1 transgenic mice cannot be made fat by feeding them linoleic acid because they maintain the omega-3/6 balance in cell membranes no matter how much linoleic acid they are fed. (web search - fat-1 transgenic mice endocannabinoid system) They also cannot be made to overproduce inflammatory eicosanoids. (web search - fat-1 mice eicosanoids)
While high linoleic acid intake for humans may decrease heart attack risk early in life, high levels of circulating linoleic acid often cause varicose veins. https://yelling-stop.blogspot.com/2016/07/varicose-veins-and-linoleic-acid.html
Varicose veins are associated with a lower risk of CVD. Excerpt: "In the NAS population, men with VV were less likely to develop symptomatic CHD over the 35+ years of follow-up than were subjects without VV. https://www.sciencedirect.com/science/article/abs/pii/S0890509606613915
Note, however, that varicose veins are associated with an elevated risk of congestive heart failure later on in life. https://pubmed.ncbi.nlm.nih.gov/20087281/
So, increasing linoleic acid intake to prevent CVD is like jumping from a frying pan into a slow cooker.