Herbal products: plant chemistry, interactions, and evidence
A plant's natural origin does not guarantee that a preparation is safe or free of side effects. Herbal products contain biologically active substances, and their effects depend on the product, its composition, and interactions with other substances. Evidence varies substantially between ingredients. Some supplements have been studied extensively, while others have little reliable research. A preparation used in a clinical study may also differ from one sold in a shop or online. The shared plant name does not establish that the products contain identical mixtures or have identical effects.
Herbal products sold as supplements belong to the broader dietary supplement category. In the United States, supplements can contain vitamins, minerals, botanicals, amino acids, enzymes, and other dietary substances. They are intended for ingestion and are sold in forms including capsules, tablets, liquids, and powders. A cream or an inhaled product is not a dietary supplement under that definition. Products also contain ingredients such as binders, fillers, flavorings, and preservatives. A label's central botanical ingredient therefore describes only one part of the finished formulation.
The regulatory framework differs from the approval process for drugs. Under the Dietary Supplement Health and Education Act of 1994, the FDA does not approve supplements before they reach the market. Manufacturers are responsible for lawful products and accurate labeling, and manufacturing rules address identity, purity, strength, and composition. Some new dietary ingredients require advance notification containing a basis for expected safety. That requirement differs from approval of every finished supplement. A product can consequently be marketed without having undergone the same premarket review as a prescription or nonprescription medicine.
Research findings and product quality can diverge. NCCIH notes that herbal products and other supplements bought by consumers may differ in important ways from those tested in studies. Some products marketed for bodybuilding, weight loss, or sexual enhancement have contained prescription drugs or other undeclared ingredients. The FDA can take action against adulterated or misbranded products, but it cannot test every product on the market. Safety also depends on the user and circumstances: interactions with medicines and limited testing in pregnancy, nursing, or children leave additional uncertainties beyond the identity of the herb.
St. John's wort illustrates the complexity. The plant, Hypericum perforatum, has a long history of use for mental health conditions and is sold as a dietary supplement in the United States. Research on depression has produced mixed results. A review of 29 international studies suggested benefit for mild to moderate major depression, while several U.S. trials did not find superiority over placebo. The studies differed in populations and settings. The 2008 review reported more positive findings from studies in German-speaking countries than from studies conducted elsewhere, including the United States.
Its interactions are also significant. NCCIH says St. John's wort limits the effectiveness of many prescription medicines, and that combining it with certain antidepressants can lead to a potentially life-threatening increase in serotonin. Reported side effects include digestive symptoms, dizziness, headache, and sensitivity to sunlight. The amount of long-term evidence is smaller than the short-term evidence. It can reduce the effectiveness of medicines including some contraceptives, transplant medicines, and treatments for HIV. Different products and combinations have therefore raised concerns about both reduced drug action and excessive combined effects.
Ginkgo supplies another example. Most modern products use an extract of the leaf, while the raw plant and seeds have different safety profiles. Leaf extracts have generally been well tolerated in adult studies, with headache, dizziness, and digestive symptoms among the commonly reported effects. NCCIH says ginkgo may increase the risk of bleeding in people who are taking anticoagulant drugs, such as warfarin, and may also interact with other drugs. Serious reactions have occurred after ingestion of seeds or crude plant material. Leaf extracts have been studied for as long as 6 years; fresh seeds are toxic, and serious reactions have also followed roasted seeds.
The evidence for ginkgo and memory also depends on the outcome being studied. In the Ginkgo Evaluation of Memory study, more than 3,000 adults aged 75 or older received ginkgo or placebo for a median of 6 years. Participants had normal cognition or mild cognitive impairment at enrollment. Rates of dementia and Alzheimer's disease did not differ between groups. Evidence about possible effects on existing dementia symptoms is inconsistent, and studies of cognitive enhancement in healthy people are often limited in quality. Preventing dementia, changing symptoms, and enhancing normal cognition are separate research outcomes.
Labels on herbal products sold as supplements can make different kinds of claims. A structure/function claim concerns normal body processes, while a health claim describes a relationship between a substance and disease risk. Disease-treatment claims belong to the drug framework. The legal category and wording of a claim do not establish the result of a clinical trial.
- NCCIH, Using Dietary Supplements Wisely — www.nccih.nih.gov
- FDA, Questions and Answers on Dietary Supplements — www.fda.gov
- NCCIH, St. John’s Wort and Depression: In Depth — www.nccih.nih.gov
- NCCIH, Ginkgo: Usefulness and Safety — www.nccih.nih.gov