I worry most about bacterial contamination since I all my chronic health complaints disappeared completely in the 8 months I've been eating large quantities of supermarket beef. I avoid any beef I don't like the looks of, since my first 20 years of buying was before the use of antibiotics and growth hormones.
Although it's not labeled healthy, there's one market in my area that carries local produce and I noticed their beef/poultry looks just like the old days and also tastes better. They even have bags of pork rinds that are in large, irregular pieces rather than machine cut and have fabulous smell and taste compared to the tasteless big brand ones. Make sure you check out all smaller local markets because you never know when you'll stumble across a gem!
A lot of my supermarket beef goes in the slow-cooker. If I choose to slow-fry (setting 4 out of 9) I usually pull apart the lean pieces divided by fat. The fat gets rendered first to provide liquid fat for the pan and the pieces get seared around the edges and then slow-fried to medium.
I asked a similar question recently about CAFO beef liver vs. grassfed beef liver, and the few answers I received confirmed my perception that very few people in the Paleo community have knowledge about toxin levels in grassfed or CAFO beef products: http://paleohacks.com/questions/84026/how-to-prepare-cafo-beef-chicken-liver-if-it-has-significant-toxin-levels#axzz1h6ywz8D3
The best article I read about the subject (although it was about beef liver specifically, the information could easily be extrapolated to any beef cut) was this: http://www.marksdailyapple.com/does-the-liver-store-toxins/#axzz1gjYLpVTd
The statement of most interest to me in the above article: "Livestock, even CAFO livestock, just aren’t exposed to toxic levels of heavy metals." I am more concerned about the hormones and antibiotics in CAFO beef products than the toxins, unless you classify the hormones and antibiotics given to CAFO cows as toxins, because they have toxic effects on our bodies. My opinion is that as long as CAFO beef products are a cheat and not a staple in your diet you should have nothing to worry about - i.e. follow the 80/20 rule advocated by Kresser and Sisson among other respectable Paleo experts.
Just the growth hormones and antibiotics. And the less favorable n6/n3 ratio. And if they are badly treated when killed, they could have other hormones elevated (cortisol, epinephrine, etc).
That's all I can think of atm.
I suppose E coli tends to be more of a problem in regular (grain fed) beef.
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