People often put Tim Ferriss and me in the same biohacker category, for good reason. We’re both after outsized gains with little effort. After I presented at the Quantified Self conference earlier this year, a few people were calling for a Bulletproof vs Four Hour debate. The truth is that I bought 30 copies of Four Hour Body the day it was released, and I’m a big fan…of the exercise related chapters.
The nutrition chapters of Four Hour Body were better than most books, but not consistent with a program that will lead to optimal health, longevity, and cognitive performance over the long term. Beans work great when you’re under 40, for a while…but they’re nowhere near optimal, as just one example. And then there’s grapefruit, which Tim recommends eating daily because it can keep you leaner because it has a chemical called naringin in it. That’s true.
There’s just one problem with grapefruit. It’s not healthy.
The July 31, 2007 British Journal of Cancer reported on a study of about 46,000 women from different ethnic groups, past menopause, with no history of breast cancer. The research was done by the University of Southern California from 1993 to 2002. Women who ate the most grapefruit – only 1/4 per day, less than Tim Ferriss recommends in Four Hour Body – had a 30 percent higher risk of breast cancer than grapefruit-free women. Controlling for weight, family history breast cancer, or hormone replacement therapy did not change the results.
USC researcher referenced a few earlier studies that showed higher levels of estrogen in women who ate a lot of grapefruit or drank its juice. Even the biohacker’s enemy, the FDA, knows about this and insists on safety labels for hormone replacement pills warning about grapefruit. And for example, I’m on a drug right now that is made much more potent by grapefruit, to the point I would dramatically increase the risk of side effects if I ate grapefruit right now.
What you should know about grapefruit and your liver
The Bulletproof Diet is not just a paleo variant; it came about from the ground up, designed using anti-aging and biochemistry principles to avoid taking toxins into the body from food and to accelerate the destruction and removal of toxins that enter the body, so I looked long and hard at grapefruit. It’s not bad for you on occasion, but daily or several time a week will change your toxin levels for the worse. There’s a reason that caffeine lasts longer when you take it with grapefruit. The grapefruit slows your intestine’s (and probably liver’s) ability to destroy the caffeine – and everything else it is detoxing with the same pathways!
Grapefruit doesn’t just have naringin as an active ingredient. It has toxins like bergamottin and another chemical called paradicin-A. (it’s misspelled on Wikipedia as paradisin, and Wikipedia won’t let me fix it since I use a proxy.)
Grapefruit slows your body’s P450 detox mechanisms, specifically your CYP3A4 function (no relation to C-3PO by the way). Cytochrome P450 is a group of enzymes in the liver. Cytochrome P450 is on the inner membrane of the mitochondria of liver cells. Mitochondria are the powerplants of cells that store oxygen to fuel the cell. (Lots of the bulletproof program involves increasing and optimizing mitochondrial function too.)
Now it’s time to get all technical – courtesy of Wikipedia:
The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances such as drugs and other toxic chemicals. CYPs are the major enzymes involved in drug metabolism and bioactivation, accounting for ~75% of the total number of different metabolic reactions.
Ok, so what the USC breast cancer grapefruit study found was that people on toxic fake hormone replacement drugs couldn’t detox them, so got breast cancer more often. You may assume that, since you aren’t on those drugs, you’re safe. But that’s missing the point.
Are you exposed to other toxins? Of course you are. And your body must detox them. If you inhibit P450 by eating grapefruit every day, whatever toxins you’re exposed to won’t be as easy to oxidize and excrete. They’ll build up. Your odds of getting sick go up because your toxic burden goes up. In fact, the epidemic of mycotoxin contamination is a major contributor to chronic health problems including cancer. Guess what? According to the Preclinical Development Handbook: ADME and Biopharmaceutical Properties, the CYP34A enzymes that grapefruit inhibits are also used specifically to detox aflatoxin and ochratoxin, two of the most dangerous mold toxins present in many processed foods today, especially if you’re not 100% grass-fed.
So what do I do? I eat grapefruit occasionally – maybe 1 every couple weeks because it is good. But almost every day, I take liposomal glutathione to keep my liver humming along at higher performance levels than would otherwise be possible. Glutathione is the main enzyme needed to detox stuff in the body – especially the liver – and liposomal makes it possible to pass the GI tract without being digested. The form on upgradedself.com was invented by a physician friend of mine, who validated that the liposomal form could raise blood levels of glutathione as much as an intravenous dose would.
So by all means, eat some grapefruit. Just don’t do it to lose weight; it’s unnecessary and increases your toxic burden. Next up on my Four Hour Body hit list is garlic. It’s far to the right on The Bulletproof Diet for a whole list of reasons, which will be the topic of another blog post.






Silicon Valley investor, computer security expert, and entrepreneur who spent 15 years and $250,000 to hack his own biology. He upgraded his brain by >20 IQ points, lowered his biological age, and lost 100 lbs without using calories or exercise.
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