 Suppose you're on the hottest new reality game show on TV. We'll call it, Would Ya Eat It? The host, a man composed entirely of perfect teeth and focus-grouped hairstyle, offers you two choices. You can choose Door 1, behind which is a grilled swordfish steak with a butter sauce. Or you can choose Door 2, behind which is a grilled collection of Everything, found in 10 cubic kilometers of seawater from the North Atlantic. The host points out that Door 2 might contain some lobster, and is likely to contain a much larger portion of swordfish than Door 1. But the catch is that, regardless of your choice, you must eat all the seafood behind that door to win the million-dollar prize. Which door would you choose? I think you'd be a fool to choose Door 2. There's no telling what will be in 10 cubic kilometers of ocean. Depending on where they've sampled, you could get a sea snake, a blobfish, sea star. The dish may be poisonous or toxic. Mixed into that may be some great stuff, but you'll have agreed to eat a lot of things you probably don't want to. Now imagine that this show is about medicine. You can choose between a purified plant product, a chemical, with known pharmacological effects, or you can eat the whole plant to treat your disease. For the most part, I think it would be unwise to eat the whole plant without knowing what else you're getting along with it. And yet, millions of people make the decision to go with Door 2, because they think it's safer to eat a plant than a chemical. How many times have you heard someone say something to the effect of, I prefer to take echinacea because it's all natural, or I worry about how toxic medicines are, so I use B-pollin to treat my asthma? There's something of an anti-medical, anti-science undertone to these kinds of comments. Another favorite is, people have been using spirulina for centuries to control their diabetes. I want to give you three examples of natural products and the evidence about their effectiveness and safety. Along the way, we'll try to separate the wheat from the chaff about herbal cures. The first example is Taxol. And this is really one of the wonderful cases that typify drug development from natural products. It was discovered by the National Cancer Institute at the construction of what is called a compound library from botanical sources. These libraries consist of hundreds of thousands of vials of chemical, obtained in various ways from natural products and represent one of the richest sources of new drug leads. Taxol was a small compound that was a very minor component of the bark of the Pacific U tree. In some early tests of crude mixtures, the Pacific U extract was very effective at killing cancer cells growing in a flask. That got it flagged for further analysis and purification. To make a long and fascinating research story very short and uninteresting, Taxol was finally isolated and characterized after almost 30 years of work. It's been a major innovation and a frontline drug for cancer intervention of a broad spectrum of patients and cancers. If you decided you prefer to get your Taxol from natural sources, you'd need to eat the equivalent of about 60 pounds of Pacific U bark for a single gram of Taxol. Okay, so you're not going to do that, so you decide to make a natural extract of the bark. For that, you'll need ethyl alcohol and a derivative of castor oil, another natural product, called cremaphore EL. This is a very toxic substance and represents the dose limiting component of conventional Taxol therapy, which is just a bark extract after all. Fortunately, researchers have developed two alternatives to the very toxic natural substance. They have a modified delivery system that uses albumin protein found in chicken egg whites to deliver the Taxol, which greatly reduces the toxicity. This formulation is called a Braxane. They've also developed a semi-synthetic form called Taxotir that can be synthesized from the more environmentally friendly English U and actually has a longer mechanism of action and slightly reduced side effects. In the case of Taxol, the natural product certainly kicked off a major discovery in cancer treatment, but the source material, Pacific U bark, is a non-viable therapeutic. Anyone who tries to sell you natural U tree extract isn't doing you any favors. Our next example is St. John's wort. I'm going to use this as a counter example to Taxol. St. John's wort is that rare exception where the herb is sometimes superior to the drug. In Germany, this herbal product is very commonly used to treat major depression. In some, but not all, clinical studies, it was superior to a placebo, had fewer side effects, and performed as well as the pharmaceutical standard of care. We should take this with a grain of salt. Antidepressants are an area of medicine that may not be very evidence-based, so the responses we get from either drug or natural product are going to be strongly affected by the accuracy of the underlying diagnosis. There are some studies that show St. John's wort to be no better than a placebo, including one by the major U.S. altmet group, the National Center for Complementary and Alternative Medicine. It's also been observed that studies in Germany, where St. John's wort is part of the folk medicine tradition, are much more likely to find a positive outcome than non-German studies. This suggests a bias or experimental design issue that should be addressed. The mechanism of St. John's wort is not well known. It's been measured to reduce serotonin reuptake, but the active ingredients have never been successfully purified. It's not without its side effects, although they're usually slightly less than the SSRI-based modern antidepressants. St. John's wort is very toxic to cattle, horses, and other grazing animals. It's especially bad for the young and can cause failure to thrives, skin lesions, and even coma at higher dosages. That kind of information is important when considering whether the herbal therapy is, in fact, safer than the pharmaceutical alternative. The most important human side effect is photosensitization, either directly or through toxic effects in the liver. Exposure to sun can result in skin lesions. The active ingredient in the herbal remedy is found in breast milk, so it should never be used with nursing mothers. You'll notice that these warnings sound an awful lot like the kind of warnings you might hear in a drug commercial. There's a reason for that. Any molecule that inhibits or in any way interacts with biological functions is going to have a side effect. That's inherent in the way our biochemistry is multifunctional. A drug and an herb that interfere in the same pathway are going to have similar side effects. It's only our perception that supposes that because something is leafy and green that it's somehow less toxic. Many plants develop toxins as a defense mechanism. Those toxins interfere with normal functioning physiology. When we come along and co-op that toxin to provide a specific kind of interference, we shouldn't be surprised that the effects can still be toxic. Red yeast rice is fermented white rice that has a coating of fungus called monascus purpurius. It's used in traditional Chinese cooking and medicines, and imparts a red color and slightly nutty flavor to dishes, including peaking duck and red rice wine. In the 1970s, researchers extracted an active ingredient from the monascus fungus called monocolon K. Chemical tests showed it to be chemically identical to the patented drug lovastatin, marketed by Merck as Mevacor. This was one of the key statin drugs that were shown to lower bad cholesterol and decreased risk of a second heart attack after the first one. The Merck product, Mevacor, was produced from a related fungus mold called aspergillus. Red yeast rice has been very poorly studied in the US and Europe. Clearly, it has a biological effect through the monocolon K, but there are dozens of other monocolons where the effects are not known. They might be beneficial, or they might be very harmful. Unfortunately, the effect of dose required is quite high. You're not going to get in a normal Chinese diet. It must be in the form of supplements. This is why I used the analogy of the game show at the beginning of the video. Our choice is to use the expensive purified product or to take a cheaper, complex mixture of possibly active components. My own choice would be for the well-characterized purified product, but not everyone agrees, and a good case can be made that the cost-effectiveness of red yeast rice makes it a good substitute for those who can't afford pharmaceutical statin regimens. Legally, red yeast rice is in limbo in the US. You can buy it in food form, and there's a gray area of food supplements that don't advertise any benefits. But the FDA has come down on the import of certain products with high monocolon content. There's also a second issue that has to do with adulteration. Due to the cost of fermenting the rice in batches, some manufacturers stretch the product with industrial red dye. Food product regulation in China may not be up to the task of ensuring quality of a product used as a pharmaceutical. Side effects of red yeast rice are similar to the purified statin drug, and can include muscle pain, cramping, and liver damage. To conclude, while natural products are of great benefit to our ability to treat disease, they represent a mix of unknown and known compounds and are not subject to the same level of testing and regulation as pharmaceuticals. That creates a potential risk that might be avoided by isolation and purification of active components. A good case can be made about the accessibility and cost of those natural cures that have undergone rigorous testing, but the potential toxic effects should also be included in the analysis. My own advice, as always, is to ask a trusted physician before you start eating any green and leafy that doesn't come in a salad. Don't be suckered into believing that just because something grew in the dirt, it's good for you. If you don't believe me, go help yourself to a big bottle of castor bean oil or syrup of epicac, and tell me how that works for you. Thanks for watching.