Activities and Applications of Emerging Herbal Preparations
“Nutraceutical” is an umbrella term, often used interchangeably with “functional food”. Nutraceuticals are foods, food ingredients, or dietary supplements (DSs) with benefits beyond basic nutrition. They include functional and fortified foods, fiber products, herbs that are not primarily medicinal, amino acids, vitamins, and minerals. Regulated differently in different countries, they have varying routes to approval and histories of use. In traditional medical systems, foods are often used medicinally, and medicinal herbs or vegetables are often used in foods. There is an overall lack of regulation globally. Often, there is conflicting evidence for claimed benefits of nutraceuticals, with a paucity of clinical trials. Sales of botanicals vary from annually depending on many factors. Some may have new reports of efficacy; for others, popularity has other roots. Sales data, lacking for many areas, are unreliable where available due to varying definitions and range of outlets.
Extracts from a 2018 report list 2017’s top 20 herbal nutraceuticals via mainstream multi-outlet channels in the United States (US), with percentage changes from 2016 and sales rankings (Table 1).* Eight top herbal nutraceuticals sold via natural channels (not in Table 1) with percentage changes from 2016-2017 form Table 2. Herbal DSs sales were >$8 billion. Most increased were for turmeric (Curcuma longa, Zingiberaceae), +46.7%; wheat (Triticum aestivum, Poaceae)/barley (Hordeum vulgare, Poaceae) “grass”, +44.2%; and fenugreek (Trigonella foenum-graecum, Fabaceae) seed, +35.5%. For green coffee (Coffea arabica, Rubiaceae), -38.2%; coconut (Cocos nucifera, Arecaceae) oil, -34.9%; green tea (Camellia sinensis, Theaceae), -30.4%; plant sterols, -27.8%; açai (Euterpe oleracea, Arecaceae) berry, -27.8%; and chia (Salvia hispanica, Lamiaceae) seed, -26.6%, sales declined. Leading the US natural channels market, cannabidiol (CBD; from cannabis [Cannabis sativa, Cannabaceae]), sales rose 303.0% (>$7.5 million). Fourth-ranked nigella (Nigella sativa, Ranunculaceae) seed sales rose 202.5% ($4.6 million). No products in Table 2 lost significant sales from 2016 to 2017.
Products with global sales much higher than in US reports and likely to rise comprise Table 3. They are astaxanthin (AX; from a green micro-alga [Haematococcus pluvialis, Haematococcaceae] and other marine species, yeasts, and bacteria), 2016-2018 sales ~$513 million, for eye health and against macular degeneration; monk fruit (luo han guo; Siraitia grosvenorii, Curcubitaceae), ~$380 million, a low calorie sweetener; mushroom β-glucans, ~$411 million, for immune support and hypercholesteremia; and Asian ginseng (AG; Panax ginseng, Araliaceae)extracts, with “huge” sales. Used for cognitive impairment and adverse effects (AEs) of radiotherapy, AG extracts are also being studied in China for adaptive effects for outer space. In 2014, Chinese Material Medica sales were >US $120 billion. Goji (Lycium chinense, Solanaceae) berry, AG, reishi (lin zhi; Ganoderma lucidum, Ganodermataceae) mushroom, and American ginseng (P. quinquefolius) led.
Five products are detailed. AX, a xanthophyll carotenoid and red pigment eaten by fish and crustaceans, is found in seafood and fish eggs. Fed to farmed fish, it gives their flesh a red color. Antioxidant and anti-inflammatory, AX modulates signaling pathways of inflammation and apoptosis. It may be useful against hepatic, retinal, cardiovascular, and neurological injury. Lacking traditional use, AX is supported by clinical trials in atherosclerosis, cancer prevention, vision disorders, dermatological conditions, and a sports supplement. Some regulators allow limited AX health claims. Natural AX has cis and trans isomers of 3,3′-dihydrxy-β,β-carotene-4,4′-dione; synthetic AX, only trans. For natural AX, no safety concerns are known. Synthetic AX concerns in vivo are likely model specific, but residual chemicals may pose risks.
CBD, the best-known non-psychoactive cannabinoid, with no abuse potential, has many biological effects. Epidiolex (GW Pharmaceuticals; Cambridge, England), a 99% CBD oral extract, is approved in the US for rare epileptic conditions. However, a plethora of CBD-containing products are unregulated in content, purity, or dosage. Soaring sales followed broad publicity on CBD in epilepsy and as an anxiolytic and analgesic. Supplies were boosted by legislation allowing cultivation of CBD-rich cannabis (“hemp”). A 2019 review of CBD alone in pain relief found three trials. Two were of such poor quality as to be useless; the third, a double-blind, crossover randomized trial, found significant pain control improvement with CBD. A systematic review in mood disorders found “scarce” evidence. Preliminary trials in inflammatory bowel diseases had conflicting results. Long believed to be entirely safe, randomized CBD trials in patients with multiple sclerosis report mild AEs and resolvable interactions. As with other products affected by cannabis prohibition, neither the safety nor efficacy of marketplace CBD products has been tested.
Monk fruit has long use in Chinese medicine, mainly for respiratory conditions, and is a juice source. As a diabetic-safe sweetener, human data are scarce, but glucose-lowering effects are seen in vivo. With low toxicity, work is ongoing to develop monk fruit as an alternative sweetener.
AG extracts, e.g., dammarene saponins and ginsenosides, an enormous market, are used for many indications and in many forms. AG products are linked to improved memory, less cognitive disability after trauma, and neuroprotection.
Nigella, used as food and medicine since antiquity, is used in Ayurveda, Unani, Iranian medicine, and other traditions. Since 2009 there are increased reports of its benefits in atherogenesis, glucose metabolism, lipid profiles, and asthma. Clinical evidence is “not especially strong” for any indication. Nigella’s thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone) has anti-inflammatory, immunomodulatory, and anti-cancer effects. Rigorous trials are needed of its value as a nutraceutical.
Table 1 lists nutraceuticals only, excluding top-selling herbs used mainly as medicines. Sales rankings are as nutraceuticals and, parenthesized, as “herbal supplements,” as seen in the extracted study.
Williamson EM, Liu X, Izzo AA. Trends in use, pharmacology, and clinical applications of emerging herbal nutraceuticals. Br J Pharmacol. March 2020;177(6):1227-1240. doi: 10.1111/bph.14943.