What the research says about natural drugs — why “efficacy” has been minimized.

“Evidence-based medicine” relies on the use of the best available scientific research to guide decisions about patient care. This is crucial to disease treatment and knowing whether something is helping or hurting you. For supplements, that information is largely missing or hard to find — and that is what LYRX sets out to fix.

Taking an untested supplement is purely hopeful and no reliable outcome should be expected. These products can also be dangerous, as supplement quality is often unregulated. If a product lacks a USP, NSF, or ConsumerLab verification mark, its strength and purity cannot be independently confirmed. As such, side effects should be watched carefully, as a lack of testing and quality control, means that no reliable information is available on side effects.

It should be mentioned however, that this handbook is still a working document and new entries will be added as additional supplement data is identified. These can be highlighted to the author through Discussion.

Supplements are sold as “healthy dietary enhancements” and are essentially manufactured products intended to add nutrients or other dietary components to your daily intake. They can be grouped into two classes with very different purposes; 1) dietary supplements, such as vitamins and minerals and 2) medications designed to treat or help unique medical conditions, or natural drugs. Dietary supplements may help promote optimal metabolism and prevent deficiency symptoms. Their efficacy is hard to measure and so most consumers simply hope they may have some utility to maintain and/or restore health. Medications, or natural drugs, are taken to treat or improve a medical condition. Some measure of the response or outcome should be taken to determine if the medication is helping or hurting. These kinds of supplements should not be taken purely with the hope that they may have a benefit.

Taking a natural drug without knowing its dose, efficacy, or side effects carries significant health risks, including organ damage, dangerous drug interactions. Fat-soluble vitamins (such as Vitamins A, D, E, and K) and certain minerals do not flush out in urine; instead, they accumulate in your liver and fatty tissues. Excess intake can lead to liver damage, bone pain, nerve damage, kidney stones, and severe toxicity. Supplements can also dangerously alter how prescription medications work. For example, Vitamin K can reduce the effectiveness of blood thinners like warfarin, while St. John's wort can weaken antidepressants, birth control, or heart medications.

Thousands of supplements are being sold online and consumed by the public, with the hope that these naturally occurring substances may have some utility to maintain and/or restore health. Consumers purchase these products blindly, without the awareness that the drug can cause unexpected side effects, allergic reactions, and dangerous drug interactions. Treatment success is generally unclear or very low.

Medical doctors are reluctant to prescribe supplements, or natural drugs, because they are not viewed as "evidence-based medicine". Pharmaceuticals are rigorously tested through randomized controlled drug trials, to illustrate the dose, response and safety of the drug. Supplements really should be called or natural drugs, because as with drugs, they can both be therapeutic and toxic. While these products can have a reasonable safety profile, some can be very dangerous, particularly when taken with other medications. Consumers are taking these dietary supplements blindly, with no idea of whether they are helping or hurting. Consequently, health professionals often view supplements as inconsequential, but potentially dangerous.

Natural substances and unmodified natural drugs are generally not patentable under patent law (such as U.S. 35 U.S.C. § 101) because laws of nature, natural phenomena, and products that already exist in nature are considered judicial exceptions to patent eligibility. Patent protection is critical to drug development because it grants companies a temporary monopoly. This exclusivity allows developers to recoup the billions spent on research and clinical trials by protecting them from cheap, immediate copying. Developing a new pharmaceutical is a long and expensive process where ~90% of drug candidates fail during clinical trials. A strong patent portfolio gives investors the guarantee of future returns, which is essential for funding early-stage biotech research.

To get a patent, a company must publicly disclose the drug's exact chemical makeup and how to manufacture it. This public disclosure prevents researchers from duplicating efforts and accelerates follow-on scientific discoveries. The premium revenues gained during the period of patent protection are claimed to be important to be reinvested into discovering the next generation of life-saving medications. Patents serve as tangible assets that allow smaller research labs to license their discoveries to larger pharmaceutical corporations with the resources to run large-scale global clinical trials.

Prescription and over-the-counter drugs must go through years of expensive, large-scale clinical trials and rigorous FDA scrutiny to prove they work and are safe for specific diseases before they can be sold. This kind of testing of a supplement will not ever be done. Both the high cost of testing and the inability of the developer to protect (patent) the drug render this kind of development unaffordable. However, since many supplements already have a reasonable safety profile, the determination of the dose per response and safety for a supplement would not be that costly to determine. And once known, these products could open a wealth of therapeutic opportunity for treating human disease.

Pharmaceutical companies are moving away from traditional large-scale, one-size-fits-all clinical trials due to escalating costs, scientific shifts toward targeted therapies, and structural bottlenecks. Developing a single traditional drug can cost hundreds of millions of dollars. Large-scale trials suffer from chronic recruitment, retention, and site-activation delays, making massive footprints financially unsustainable. Companies are heavily shifting focus toward oncology, genetic disorders, and orphan diseases (affecting small patient populations) rather than mass-market chronic conditions like heart disease or diabetes. Studying thousands of patients in massive trials is unnecessary or impossible for ultra-rare conditions.

Large pharmaceutical manufacturers contend that high research and development (R&D) costs, estimated to be over billion dollars per drug, must be recouped through market returns. And since roughly 90% of drug candidates fail during clinical trials, companies argue that financial pressure restricts their ability to fund speculative or less-lucrative categories like rare infectious diseases. Studies by organizations like the USC Schaeffer Center and projections cited by the National Center for Biotechnology Information suggest that reduced expected revenues or compressed margins can lead larger firms to cut back on R&D or abandon high-risk candidates in early phases (Phase I and Phase II). Skyrocketing clinical trial expenses, intensified by fierce competition for patient enrollment and stricter regulatory requirements, push companies to favor incremental variations of proven biological pathways rather than high-risk, ground-breaking cures. The era of blockbuster drugs, like the statins, appears to be over.

Public health agencies and national research councils allocate tax-funded grants specifically for studying natural products, herbal extracts, and traditional medicines. For example, initiatives backed by public health bodies or global health organizations (such as WHO-supported traditional medicine research programs) fund laboratories and clinical trials to validate indigenous and natural remedies. Public health authorities, such as national food and drug administrations, may provide scientific guidelines, purity standards, and analytical frameworks to help developers transform raw herbal mixtures into standardized pharmaceutical products. Some universal health care systems evaluate proven natural and herbal extracts for inclusion in national Essential Medicines Lists. Once approved, these drugs gain a clear, reliable pathway to public procurement and reimbursement, lowering commercialization risk for developers.

The drug market operates under the fundamental principles of supply, demand, pricing, and distribution. As expected, treating drugs as commodities prioritizes profit over public health. This economic framework creates and deepens systemic inequalities. Newer and more effective drugs are becoming unaffordable. Approximately 90% of drug candidates that enter clinical trials fail to reach the market due to lack of clinical efficacy and unmanageable toxicity. This high failure rate makes developing a single medication take up to 15 years and cost over $1 billion. This high developmental cost translates into very expensive drugs, for the few that can afford them.

This poorly designed system forces the drug developer to charge the maximal amount for their finished drug product. For them, this is a reasonable "return on investment" for the cost of development. This system has now been clearly shown to not work. Modern pharmaceutical pipelines have moved away from large scale, blockbuster clinical trials and now focus on oncology, gene therapy, and rare orphan diseases, which feature small, defined patient subsets rather than massive broad populations. An incurable disease that can be treated with a specially designed drug will allow for a very high price tag, to treat the "live or die" disease. This is a disastrous direction for modern medicine to take.