Learning about drug metabolism, P450 system is used to detoxify toxic substances in the liver, so I wondered if grapefruit are harmful on its own, and there is an association, but it could be because it affects drug metabolism, or other residual confounding.

When compared with non-consumers, frequent consumers of red wine, tea, peppers, blueberries and strawberries were at reduced risk of all-cause mortality (P<0·05), with the strongest associations observed for red wine and tea; multivariable-adjusted hazard ratios 0·60 (95 % CI 0·49, 0·74) and 0·73 (95 % CI 0·65, 0·83), respectively. Conversely, frequent grapefruit consumers were at increased risk of all-cause mortality, compared with their non-grapefruit consuming counterparts (P<0·05).

Considering threads like this:

and that Brian Kennedy has wondered that it could increase side effects with rapamycin use, compared with equivalent dose without it, might be important to consider or research further.

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Q1. Could increased all-cause mortality have been caused by severe interaction between GFJ and many other drugs - and thus overdose because users were unaware of this interaction and did not inform their pharmacy of prescribing doctor about GFJ. and/or
Q2. Could GFJ maybe preferently be used by persons having health risks.

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This sucks. I eat a grapefruit every day. Not too worried though.

I think everyone I know that eats grapefruit drowns it in sugar. Maybe that’s a link.

I just cut it into six pieces and eat it off the rind.

They adjusted for a bunch of things that probably controlled for any confounding sugar consumption, all adjustments are to the right in the image, e.g “Alternative Healthy Eating Index”, energy intake, BMI, etc.

“grapefruit had a small positive association with all-cause mortality. This inverse association may be due to the contribution of sugar-rich juices to total grapefruit intake. Furthermore, this detrimental association may also be explained by be due to the findings that grapefruit components have clinically significant interactions with drugs, which appear to be independent of their flavonoid content( Reference Huang, Hall and Watkins34 ). However, this hypotheses were unable to be explored in this cohort.”

Orange juice had a non-significant reduction in all-cause mortality though. So the grapefruit association could be because of added sugar to juice but I think it’s more likely it’s the powerful inhibition of CYP3A4.

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