Bioavailability

A single glass of grapefruit juice can increase the bioavailability of certain medications by up to 500%, sometimes turning a therapeutic dose into a toxic one. The culprit is bergamottin, a compound that disables CYP3A4 enzymes in your intestinal wall—the very enzymes responsible for breaking down many drugs before they reach your bloodstream. This discovery emerged accidentally in the 1990s when researchers used grapefruit juice to mask the taste of alcohol in a drug study, only to find their subjects experiencing unexpectedly powerful effects. It's a vivid reminder that what you consume alongside a supplement or medication can matter as much as the substance itself.

When you swallow a supplement, it faces a brutal obstacle course: stomach acid, digestive enzymes, intestinal bacteria, and then the liver—which treats many compounds as toxins to be neutralized before releasing them to the body. This "first-pass metabolism" is why some oral drugs have bioavailability as low as 5%, while the same compound injected directly has 100% bioavailability. Your liver, essentially the body's bouncer, evolved to protect you from dietary toxins, but this ancient defense system now inadvertently blocks many beneficial compounds. Understanding this gauntlet explains why sublingual (under-tongue) and transdermal (through-skin) delivery methods exist—they're clever workarounds to sneak past your liver's checkpoint.

Curcumin from turmeric has remarkable anti-inflammatory properties in lab studies, yet eating turmeric alone gives you almost zero therapeutic benefit—its bioavailability is less than 1%. Adding black pepper (specifically its compound piperine) increases curcumin absorption by 2,000% by inhibiting the enzymes that rapidly metabolize it. This principle applies far beyond turmeric: fat-soluble vitamins need dietary fat to absorb, iron pairs best with vitamin C, and calcium competes with magnesium for uptake. The emerging field of "food synergy" suggests that our ancestors' traditional food combinations—like beans with tomatoes, or tea with lemon—may have evolved precisely to optimize nutrient bioavailability.

That vitamin C tablet claiming 1,000mg might deliver only 200mg to your bloodstream, while the remaining 800mg becomes expensive urine. Bioavailability varies wildly between supplement forms: magnesium oxide is cheap but only 4% bioavailable, while magnesium glycinate costs more but delivers 80%. The supplement industry isn't required to disclose bioavailability on labels, so consumers unknowingly pay for compounds that largely pass through unabsorbed. This gap between label claims and actual delivery explains why two people taking "the same" supplement can have completely different results—and why blood tests, not bottle labels, reveal true nutritional status.

Your gut bacteria don't just passively watch nutrients go by—they actively modify them, and your unique microbiome composition can make you a "high absorber" or "low absorber" of specific compounds. Some people's gut bacteria convert soy isoflavones into equol, a compound with powerful estrogenic effects, while others lack the necessary bacteria and get minimal benefit from soy. This explains the puzzling variability in supplement studies where some participants respond dramatically while others show no effect—it's not placebo, it's personalized biochemistry. The future of nutrition may involve testing your microbiome before recommending supplements, essentially prescribing based on your internal chemical factory's capabilities.

The same supplement taken at different times can have drastically different bioavailability due to your body's circadian rhythms and fed versus fasted states. Iron absorption increases by 300% when taken on an empty stomach but causes nausea, while fat-soluble vitamin D taken with a high-fat meal absorbs 50% better than with a low-fat one. Your stomach acid production peaks during meals and drops at night, affecting how well certain nutrients dissolve. Even more surprising, your gut's "clock genes" make intestinal cells more or less permeable at different times of day, potentially explaining why some medications work better when taken at specific hours. This temporal dimension of bioavailability suggests that not just what and how much, but precisely when you consume something might be the missing variable in your health optimization.