INTRODUCTION

The plant genus Lycium contains approximately 80 species distributed in Asia, South America, southern Africa, and, less commonly, temperate Europe.¹ Of the seven species that grow in China, the two primary medicinal species are L. barbarum and L. chinense, which are used interchangeably in traditional Chinese medicine (TCM),² traditional Japanese Kampo medicine,³ and traditional Korean medicine.⁴ Lycium chinense also occurs in parts of Japan (including the Ryukyu Islands) and Korea (including Jindo Island).^1,5

Both L. barbarum and L. chinense are deciduous shrubs, usually thorny, with arching or prostrate branches and alternate, lanceolate, gray-green (L. barbarum) or bright green (L. chinense) leaves. Lycium barbarum can grow to a height of almost 10 feet (3 meters) while L. chinense can grow slightly larger. Lycium barbarum has five-lobed flowers that have been described as pale rose, violet, or light purple in color, and L. chinense has flowers that are purple.^6,7 From June through September, these species produce oval red fruits that are tangy yet sweet and approximately one inch (2.5 centimeters) long.^6,8

The berries are harvested when ripe, dried until the pericarp is shrunken, then exposed to strong sunlight until the exocarp is dried and hard, but the inner pulp is still soft. The dried root bark of both species is also used in TCM.⁹ Since the fruits of the two species of lycium discussed in this article are used interchangeably in TCM, attributed uses apply to both species unless stated otherwise. This article focuses mainly on lycium fruit, although use of lycium root bark in TCM may be mentioned in context.

In the United States, the preferred standardized common name for both L. barbarum and L. chinense is simply “lycium,” according to the second edition of the American Herbal Products Association’s (AHPA’s) Herbs of Commerce. Lycium barbarum is also known as barbary wolfberry, and L. chinense is sometimes referred to as Chinese wolfberry. In the US market, lycium fruit is known as goji berry, an Americanized spelling of gou qi zi, the Chinese pinyin transliteration of 枸杞子. In Japan, lycium fruit is known as クコシ (ku ko shi) and, in Korea, it is known as 구기자 (gu gi ja or ku gi cha).¹⁰

While L. chinense is referred to simply as gou qi, L. barbarum is referred to with qualifiers, such as ning xia gou qi, which refers to the Ningxia Hui autonomous region from where most of the supply originates. The variety L. barbarum var. barbarum is widely cultivated, especially in Ningxia, but also in the city of Tianjin.¹ Bensky et al. (2004) describe three different regional types of lycium fruit grown in China: western lycium fruit (xi gou qi zi) from Ningxia, Gansu province, and Qinghai province; Tianjin lycium fruit (jin gou qi zi) from Tianjin; and local lycium fruit (tu gou qi zi), also called mountain lycium fruit (shan gou qi zi), which is wild-collected in Henan province.¹¹ Recently, metabolic profiling methods have been used to differentiate geographical origins of lycium fruit samples from China, Mongolia, and Tibet.¹² Additionally, fruits of L. barbarum and L. chinense from different regions can be distinguished based on a combination of taste pattern, Brix percentage (sucrose content), betaine, and saccharide composition analyses.⁵

Ningxia lycium that is traditionally harvested and processed is a protected geographical indication (PGI) product. When produced in compliance with the PGI standard (“GB/T 19742-2008: Product of geographical indication – Ningxia lycium”), geo-authentic lycium fruit may be labeled and marketed with the PGI certification mark issued by China’s General Administration of Quality Supervision, Inspection and Quarantine.¹³

Nearly all of the global commercial supply of lycium fruit is obtained from both wild-collection and cultivation in China,^14,15 mainly in northern to northwestern areas, especially Qinghai province and the Ningxia and Xinjiang Uygur autonomous regions, but also Gansu and Shaanxi provinces and the Inner Mongolia and Xizang (Tibet) autonomous regions.¹⁰ Although China is the only major user, producer, and exporter of lycium fruit in the global market, China also occasionally imports very small amounts from South Korea and North Korea.¹⁶ South Korea produces L. chinense fruits in the provinces of South Chungcheong and South Jeolla.⁵ Three varieties of L. chinense were developed and released in South Korea between 1997 and 2000 with improved yield, insect resistance, and saponin content: “Cheongyang Kugija” (1997), “Bulro Kugija” (2000), and “Cheongdae Kugija” (2000).¹⁷ Most of the certified organic goji berry (both farmed and wild-harvested) in the global market originates from Qinghai province and the Ningxia autonomous region in China, but some organic production also takes place in Gansu, Liaoning, Shaanxi, and Tianjin provinces, and the Inner Mongolia and Tibet autonomous regions.¹⁸ Although there are popular goji products labeled as “Himalayan,” the term “Himalayan goji” is only for marketing purposes and is not an actual geographical indication.

Hundreds of years ago, L. barbarum was introduced into other parts of Asia and parts of Europe. The first known record of L. barbarum cultivation in Europe, in what is now the Czech Republic, dates back to 1785. Having escaped cultivation, it was first reported as growing wild there in 1870, and is now considered invasive with an observed impact on native biodiversity.¹⁹ Classified as a non-native invasive species in the Danube Delta region of Romania,²⁰ L. barbarum is also reportedly encroaching on disturbed kurgans (ancient burial mounds) in the steppe zone in parts of Eurasia from the Danube Delta to Mongolia.²¹ One of the authors of this article (JB) has seen large L. barbarum plantations surrounding stone-slab tombs in the Gobi Desert.

HISTORY AND CULTURAL SIGNIFICANCE

The origin of the common name wolfberry corresponds to the Chinese name gou qi zi, as the character for gou means dog or wolf, and the character for zi means small fruit.²² The genus name Lycium appeared in 1737 with the synonym Jasminoides in the first edition of Genera Plantarum by Swedish botanist Carl Linnaeus (1707-1778).²³ Today, Jasminoides flaccidum is listed as a synonym of the currently accepted name Lycium barbarum while J. rhombifolium is listed as a synonym of L. chinense.²⁴ The species L. barbarum was named in 1753 by Linnaeus in his Species Plantarum.²⁵ The species name barbarum, the neuter gender of barbarus, stems from the ancient Greek word for foreign or barbarous.²⁶ Lycium chinense was named in 1768 by Philip Miller (1691-1771), a Scottish horticulturalist and Chelsea Physic Garden (London) botanist, in the eighth edition of The Gardeners Dictionary.²⁷

Lycium fruit was first described in the premodern classic Shen Nong Ben Cao Jing, the Divine Farmer’s Classic of Materia Medica, compiled in the first century CE.²⁸ Its medical use was later recorded in the third century CE text Ming Yi Bie Lu, the Miscellaneous Records of Famous Physicians²⁹ (also translated as Informal Records of Eminent Physicians), an anonymous work that, according to Hsu and Harris (2012), has been erroneously attributed by other authors to Daoist physician Tao Hongjing (456-536 CE).³⁰ According to Dharmananda (2007), the use of lycium fruit “in traditional formulas was rather limited until the end of the Ming Dynasty period (1368–1644)” when it was often combined with tonic substances in formulas indicated to “nourish the kidney.”²² According to an English translation of the 1970 Official Chinese Paramedical Manual, lycium fruit acts to strengthen the kidney meridian, restore semen, nourish the liver meridian, and clear vision.³¹

Additional uses in TCM include addressing diabetes, vertigo, nocturnal emissions, consumptive cough, problems with the loins and knees, sore back and legs, mild abdominal pain, infertility, prematurely gray hair, night sweats, diminished visual acuity, thirst, and wasting.^29,32,33

Since lycium is an important medicinal plant widely used in the Asian systems of medicine, quality standards monographs that provide specifications and test methods for the fruit have been published in the Japanese Pharmacopoeia,³ Korean Pharmacopoeia,⁴ Pharmacopoeia of the People’s Republic of China,⁹ and Taiwan Herbal Pharmacopoeia.² A quality standards monograph for “Barbary Wolfberry Fruit” first entered the European Pharmacopoeia (PhEur) in the fourth supplement to the eighth edition (PhEur 8.4) in April 2015, and remains official up through the current ninth edition published in July 2016.³⁴ The US Pharmacopeial Convention proposed the development of a “Lycium barbarum Fruit” monograph for its Herbal Medicines Compendium in May 2013. A draft version of that monograph is available online with a call for submission of validated information needed to complete the monograph.³⁵

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES

In Asian countries where traditional Chinese, Korean, and/or Japanese medicine are practiced, as well as in some Western countries where TCM is recognized, lycium fruit is used as an active substance indicated for general debility with deficiency of vital essence manifested by aching of the loins and knees, dizziness, and tinnitus. Additional indications include anemia, impaired vision, and diabetes caused by internal heat.⁹ Presently, in the United States, most states and the District of Columbia permit the practice of Oriental medicine with varying limitations on the scope of practice. In states where TCM formulations can be dispensed to patients, lycium fruit (or fruit extract) may be used as a component of herbal prescriptions for at-home preparation (by traditional decoction) by patients, or as a component of Chinese patented medicines, professional products, or practitioners’ formulations dispensed by compounding pharmacies.³⁶

Lycium fruit may also be used as a component of herbal dietary supplement products widely available outside of clinical practice in the United States.³⁷ While not expressly listed as Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (FDA) for use in conventional food products, “goji berry” (L. barbarum only) is accepted as a food because the Environmental Protection Agency (EPA) has established tolerances for pesticides that may be used when it is cultivated as a food crop, per its inclusion in the EPA’s “Crop subgroup 8–10A. Tomato subgroup.” (This subgroup also includes other fruits in the Solanaceae family, such as capsicum [Capsicum annuum], eggplant [Solanum melongena], and tomato [Solanum lycopersicum], among others.) This means that certain chemicals (e.g., the fungicide azoxystrobin and the molluscicide metaldehyde) are approved for application to goji berry food crops in the United States.³⁸

In Canada, lycium fruit is regulated as an active ingredient of licensed natural health products (NHPs, a category of drugs), which require pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD). “Fructus Lycii” is listed in Table 1 (General Medicinal Ingredients) of the “Natural Health Product: Traditional Chinese Medicinal Ingredients” monograph. Labels of licensed NHPs that contain preparations of pharmacopeial-quality lycium fruit may carry claim statements consistent with the indications for use provided in the Pharmacopoeia of the People’s Republic of China.³⁹ Additionally, L. barbarum fruit is listed in Appendix 3 (Other Medicinal Ingredients) of the “Natural Health Product: Antioxidants” monograph. At the specified dosage equivalent (6 g dry), licensed L. barbarum fruit NHPs may be marketed with antioxidant claim statements (i.e., “source of antioxidants that help protect against cell damage caused by free radicals”).⁴⁰ At the time of this writing (December 2016), there were 671 licensed NHPs that list “Lycium barbarum” as an ingredient, of which 624 list it as a medicinal ingredient and 47 as a non-medicinal ingredient; 114 licensed NHPs list “Lycium chinense” as an ingredient, of which 107 list it as a medicinal ingredient and seven as a non-medicinal ingredient; 40 licensed NHPs list “goji berry” as a non-medicinal ingredient; and seven licensed NHPs list “Fructus Lycii,” of which two list it as the active ingredient.⁴¹

For herbal medicinal product companies in the European Union (EU), or in non-EU countries where the PhEur is an official compendium (e.g., Australia and Canada), the quality standards monograph established by the European Directorate for the Quality of Medicines (EDQM) for “Barbary Wolfberry Fruit – Lycii Fructus” (the dried, whole, ripe fruit of L. barbarum) can be used as the basis for active ingredient specifications.⁴² Barbary wolfberry fruit is one of a total of 43 TCM herbal drugs that had been adopted in the eighth edition of the PhEur,⁴³ and this increased to 66 monographs in the ninth edition (De-An Guo email to T. Smith, January 20, 2017). The European Medicines Agency (EMA), however, has not yet developed a corresponding labeling standards monograph for statements that can be made on labels of registered traditional herbal medicinal products (THMPs) containing barbary wolfberry fruit.⁴⁴

For use in cosmetic products, the European Commission’s Health and Consumers Directorate lists “Hydrolyzed Lycium Barbarum Fruit” (hydrolysate of the fruit of L. barbarum derived by acid, enzymes, or another method of hydrolysis) and “Lycium Barbarum Amino Acids” (mixture of amino acids derived by the complete hydrolysis of the protein isolated from the whole plant) for skin-conditioning function, and lists “Hydrolyzed Lycium Barbarum Fruit Extract” for antioxidant and skin-protecting functions. “Lycium Barbarum Fruit Extract” is listed for antioxidant, hair-conditioning, and skin-conditioning functions. “Lycium Chinense Fruit Extract” is listed for antioxidant function, “Lycium Chinense Fruit Juice” (juice expressed from the fruit of L. chinense) for skin-conditioning function, and “Lycium Chinense Fruit Water” (aqueous solution of the steam distillates obtained from the fruit of L. chinense) for flavoring, masking, perfuming, and skin-conditioning functions.⁴⁵

MODERN RESEARCH

Dried lycium fruits contain pyrrole alkaloids, hydroxycinnamic acids (e.g., chlorogenic acid),⁴⁶ carotenoids (e.g., zeaxanthin and β-carotene),^47,48 polysaccharides,⁴⁶ cerebrosides, glycolipids,^49,50 peptides,⁴⁹ flavonoids (e.g., kaempferol, myricetin, and quercetin),⁴⁸ triterpenes (e.g., β-sitosterol),^50,51 and amino acids (proline, taurine, γ-aminobutyric acid, and betaine),^48,52 as well as vitamins, such as ascorbic acid, riboflavin, and thiamin.⁴⁸Lycium barbarum contains certain polysaccharides (L. barbarum polysaccharides or LBPs) that some studies suggest are the main bioactive constituents.^8,46,53,54

In vitro and in vivo studies have shown lycium fruit to be anti-inflammatory,⁵⁵ antioxidant,^56,57 antifibrotic,⁵⁸ antiaging,⁵⁹ apoptotic,⁶⁰ cerebrovascular protective,⁶¹ hepatoprotective,^58,59,62 hypolipidemic,⁶³ hypotensive,^59,62 hypoglycemic,^59,62-64 immunomodulating,⁶⁵ and neuroprotective.^66-71 Laboratory studies have also shown that lycium can cause cancer cell death (apoptosis),^72,73 inhibit growth of human breast cancer cells,⁷⁴ ameliorate physical fatigue,⁷⁵ improve insulin resistance,⁷⁶ reduce chemotherapy-induced hair loss,⁷⁷ protect against oxidative stress,^78-80 prevent prenatal stress-induced cognitive impairment,⁸¹ protect against acetaminophen-induced acute hepatotoxicity,⁸² treat age-related macular degeneration (AMD),⁸³ and significantly lower fasting blood glucose, total cholesterol, and triglycerides.^64,84 As one peer reviewer of this article noted, these research findings “do not necessarily translate to clinical results from consuming ordinary amounts of the whole fruits, their tea, juice, or commercial extracts.” Such research may, however, suggest the “possible use of isolated components of lycium fruit and possible mechanisms of action for reported clinical benefits.”

Human clinical trials have focused on L. barbarum and LBPs, and have addressed diabetes, immune health, antioxidant effects, vision (specifically AMD), metabolic rate, weight and waist circumference, general wellbeing, fatigue, and stress. As with all clinical trials of herbal products, various factors should be taken into consideration when interpreting the results. The CONSORT statement for herbal medicine interventions outlines many of these considerations (e.g., methodological quality, appropriate description of herbal intervention, potential conflicts of interest, etc.).⁸⁵ As indicated in the study summaries below, many of the tested LBP preparations lacked detailed characterizations by the authors. Additionally, many of the human trials summarized below have various design limitations that weaken their conclusions.

LBPs have been used in Chinese medicine to address various symptoms associated with type 2 diabetes, including excessive thirst and urination. A prospective, randomized, double-blind, controlled study of 67 patients who had been diagnosed with type 2 diabetes less than five years before the study examined the effects of LBPs on two other factors: postprandial glucose and lipid levels. Patients were given either 300 mg of LBPs (produced by a pharmaceutical company in Shanghai from fruit purchased from the Ningxia autonomous region; no additional information provided) or placebo in two doses per day for three months. Patients were asked to continue their normal therapy during the intervention period and had regular follow-up visits every two weeks. The oral metabolic tolerance test (OMTT) showed that the LBP group experienced a significant reduction in serum glucose and increase in high-density lipoprotein (HDL) levels after intervention, compared to baseline. The hypoglycemic effects were more significant in patients not taking hypoglycemic medicines than in those who were.⁸⁶

At least five studies have been published on the positive effects of a 120-mL daily serving of L. barbarum juice standardized to supply an LBP equivalent of at least 150 g of fresh fruit (GoChi; FreeLife International Inc.; Phoenix, Arizona). The first, in 2008, was a randomized, double-blind, placebo-controlled (RDBPC) trial in which 34 healthy volunteers took either 120 mL of GoChi or placebo each day for 14 days. Subjects were instructed to discontinue use of L. barbarum and L. barbarum-containing foods, as well as dietary supplements, energy drinks, and green tea (Camellia sinensis, Theaceae) throughout the study. Subjects received a medical exam and their physical measurements were assessed (i.e., parametric data such as body weight, body mass index [BMI], blood pressure, heart rate, etc.), as well as their history of smoking, diseases, and dietary habits. While there were no significant changes in parametric data between days one and 15 in either group, the GoChi group experienced significant improvements in athletic performance, calmness, focus on activities, sleep quality, and feelings of contentment, happiness, and good health, compared to baseline. The GoChi group also experienced a tendency toward increased energy level and mental acuity, and had a significant reduction in feelings of fatigue and stress, compared to baseline.⁸⁷

In a 2009 RDBPC study, 60 healthy, older Chinese adults (55 to 72 years old) were randomly assigned to take 120 mL of GoChi or placebo once daily for 30 days. Each subject received a medical exam, had physical measurements assessed (body weight, blood pressure, pulse rate, abdominal B-ultrasound, electrocardiogram, and chest X-ray), and provided background information that included disease history. Subjects had no acute diseases, took no long-term medications, and had no history of using GoChi. Subjects were instructed to discontinue use of L. barbarum and L. barbarum-containing foods at least two months prior to and throughout the study. Subjects were monitored to assure compliance. Both the GoChi and placebo groups experienced minimal changes in parametric data. However, significantly more subjects in the GoChi group (more than 60%) communicated increased ratings of general well-being compared to those in the placebo group (20%). While it was not statistically significant, the GoChi group also showed a tendency toward improved short-term memory and focus between the beginning and end of the study. Additionally, lymphocyte numbers and certain immunological markers (IL-2 and IgC) were significantly increased in the GoChi group, compared to baseline, which suggests that GoChi may have immunomodulatory effects.⁸⁸

Another 2009 article, which resulted from the study discussed above, reported on GoChi’s serum antioxidant effects. It was ascertained before testing that subjects in the GoChi and placebo groups had similar serum levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lipid peroxidation, as indicated by decreased levels of malondialdehyde (MDA). After 30 days of intervention, both SOD and GSH-Px had significantly increased (by 8.4% and 9.9%, respectively) and MDA had significantly decreased (by 8.7%) in the GoChi group. No significant changes were seen in the placebo group. This would suggest that GoChi has a positive antioxidant effect on humans and that use beyond 30 days might provide protection against free radical-induced conditions, such as coronary artery and neurodegenerative diseases.⁸⁹

A 2011 article reported on two small RDBPC studies: one examined GoChi’s effect on resting metabolic rate (RMR) and postprandial energy expenditure (PPEE), and the other looked at its effect on waist circumference and other morphometrics (BMI, waist circumference, and total body fat). Participants were recruited separately for the two studies and included healthy men and women with no evidence of heart, kidney, liver, or lung diseases. All participants completed a minimum two-week washout period during which they took no L. barbarum or L. barbarum-containing foods, and no dietary supplements, energy drinks, or caffeinated drinks, including green tea. During both studies, participants were monitored to ensure compliance. Results of these two studies, as described below, suggest that GoChi may stimulate metabolic rate, which may lead to a decrease in waist circumference.⁹⁰

In the first study, eight subjects were randomly assigned to take a 120-mL serving of a placebo beverage or GoChi (containing one of three doses [30, 60, or 120 mL] of L. barbarum), along with a nutritional beverage to stabilize RMR for the four-hour test period. RMR and PPEE were measured by breath oxygen volume (VO₂; mL/min) before intake, and at one, two, and four hours after intake. One week later, the procedure was repeated by each group. All dosages of GoChi and placebo increased RMR over baseline. At one hour after intake, VO₂ measurement for 120 mL of GoChi increased by 58.26 ± 5.72 mL/min from baseline and was significantly higher than the placebo group, which increased by 24.58 ± 4.04 mL/min from baseline. At four hours after intake, VO₂ levels had returned to baseline for those in the placebo group and for those taking all dosages except 120 mL of GoChi. For those taking 120 mL of GoChi, VO₂ remained significantly higher than the levels achieved by other doses or placebo.⁹⁰

In the second study, 33 healthy subjects consumed 120 mL (90 mL at breakfast and 30 mL at bedtime) of GoChi or placebo for 14 days. Caloric intake was restricted to 1,200 kcal during the intervention in both groups, and subjects took daily 15-minute walks and recorded daily steps using pedometers. Waist circumference in the GoChi group decreased significantly mid-intervention and post-intervention compared to baseline. On day 15, it had been reduced by 5.54 ± 0.65 cm compared to pre-intervention. In contrast, in the placebo group, waist circumference on day 15 had been reduced by only 0.88 ± 0.83 cm, which was not a significant change from pre-intervention. Body weight, BMI, and total body fat did not change significantly in either group.⁹⁰

A 2012 RDBPC study explored the effect of GoChi on general well-being and fatigue. After a two- to four-week washout period during which subjects discontinued use of energy drinks, caffeinated drinks, and L. barbarum or L. barbarum-containing foods, 39 healthy volunteers were randomly assigned to consume either 120 mL of GoChi or placebo in the morning every day for 30 days. Subjects were monitored for compliance. Participants also maintained a daily dietary diary and completed a short, intense exercise challenge on the first and last days of the intervention. Plasma levels of the adrenal steroids dehydroepiandrosterone (DHEA) and cortisol — which regulate numerous cardiovascular, homeostatic, immunologic, and metabolic functions — as well as glucose, blood urea nitrogen (BUN), and lactic acid were measured following the exercise challenge both pre- and post-intervention. While DHEA, cortisol, and lactic acid were increased significantly by the exercise challenge prior to the intervention in both groups, the GoChi group experienced significantly reduced DHEA and cortisol levels post-intervention compared to baseline. Glucose and BUN were not altered, and lactic acid levels were comparable in both groups. Additionally, while there were no significant changes in either group with regard to body weight or BMI, the GoChi group reported significant reductions in feelings of tiredness after exercise and improvements in circulation and general overall health, compared to placebo. This study suggests that the consumption of L. barbarum may promote adaptability to physical stressors (e.g., exercise), perhaps by limiting production and function of glucocorticoids, or by accelerating their metabolism.⁹¹

Zeaxanthin is an oxygenated carotenoid concentrated in the fovea (a small depression in the retina where visual acuity is greatest) and is one of the constituents of macular pigment. AMD, the thinning of the macular pigment that often occurs with age, is associated with loss of vision.⁹² Because zeaxanthin dipalmitate is the most abundant carotenoid in L. barbarum (3,011-9,417 mg/g in certain genotypes),⁴⁶ its antioxidant properties are being studied for their role in protecting vision, specifically in cases of AMD.

A single-blind, placebo-controlled parallel trial published in 2005 investigated how fasting plasma zeaxanthin concentration changed with L. barbarum dietary supplementation over 28 days. Heat-dried L. barbarum berries (Rich Nature Goji Berries; Rich Nature Nutraceutical Labs Inc.; Mukilteo, Washington) were extracted, and the total zeaxanthin content was estimated by HPLC to be 194 mg/g, which suggested that taking 15 grams per day of the dried berries would provide additional dietary intake of 3 mg per day of zeaxanthin. Fourteen healthy subjects softened 15 grams per day in one cup of boiling water for 15 minutes after dinner, mashed the berries, then ingested them with the water. The control group drank a cup of plain warm water. Fasting blood samples were taken at baseline and at 28 days and assessed for zeaxanthin and lutein. At day 28, while plasma lutein levels had not changed significantly, there was a significant increase in both total and lipid-standardized plasma zeaxanthin in the test group, compared to baseline. The authors conclude that the benefits of lycium supplementation are strong but that longer-term supplementation studies are needed to determine if lycium berries can increase macular pigment density and protect vision in the aging population.⁹²

Published in 2011, a RDBPC study evaluated the effects of a proprietary milk-based L. barbarum product on macular characteristics and plasma antioxidant levels in healthy elderly Chinese subjects over a 90-day period. Subjects were screened for terminal and significant chronic diseases, deteriorating health, glaucoma, cataracts, and lactose intolerance. Eligible subjects (N = 150, of which 133 completed the study) were randomly assigned to consume 13.7 g of Lacto-Wolfberry (LWB; Nestle R&D Centre Shanghai; Shanghai, China) — a product containing 530 mg/g L. barbarum fruit, 290 mg/g skim milk, 180 mg/g maltodextrin, 476 mg/g sucrose, and 34 mg/g colorants (providing 0.73 mg/g [10 mg per day] lycium-derived zeaxanthin and 5 mg/g [68.5 mg per day] lycium-derived vitamin C precursor) — or placebo with 200 mL of soup or hot water each day at lunch under supervision. Before and after intervention, detailed ophthalmic examinations of each subject assessed macular pigmentation and soft drusen count (a risk indicator for AMD) in the macula, and fasting blood samples assessed plasma zeaxanthin and total antioxidant capacity. Compared to baseline, there were no significant macular pigmentation changes in the LWB group, but 13 subjects in the placebo group showed progressive macular hypopigmentation (P < 0.001), and, at day 90, LWB subjects had significantly less macular hypopigmentation (P < 0.01). Also, while no subjects in either group had more than one soft drusen at baseline, eight people in the placebo group had a significant increase in soft drusen at 90 days, compared to no increase in the LWB group. With regard to plasma zeaxanthin and antioxidant capacity, both were stable over time in the placebo group but increased significantly in the LWB group (26% increase and 57% increase, respectively). The authors conclude that, while LWB consumption for 90 days can increase plasma zeaxanthin and total antioxidant levels and protect the macula of elderly subjects from hypopigmentation and the accumulation of soft drusen, the mechanism of action is unclear.⁹³

FUTURE OUTLOOK

There are no known comprehensive reports available on the conservation status of wild L. barbarum or L. chinense in their East Asian native habitat.

China is the largest producer, user, and exporter of lycium fruit, having exported about 9.304 million kg in 2013, of which nearly half, or at least 4.538 million kg, was certified organic (including farmed and organic wild).¹⁵ The total annual export volume is increasing significantly, up from 5.823 million kg exported in 2009. The main importers of Chinese origin lycium fruit in terms of volume are Hong Kong, Taiwan, Malaysia, the United States, the Netherlands, Vietnam, South Korea, Germany, Spain, the United Kingdom, and Japan.^10,16 China’s 2015 harvest total was estimated to be more than 200 million kg,⁹⁴ which indicates that domestic consumption for use in TCM prescriptions, as well as for manufacture of value-added processed forms (e.g., extracts, juices, and wines) is significantly greater than the export market.

Market prices are impacted by geographical origin specifications (e.g., geo-authentic Ningxia lycium PGI), quality (food-grade or pharmacopeial-grade), color, and size grading. Lycium fruits are sized in “grains (berries) per 50 grams.” The larger the berries, the fewer grains per 50 g and the higher the price. Several size grades are traded from 180 grains per 50 g up to 750 grains per 50 g, but the most frequently traded grades are 220, 280, and 380 grains per 50 g. At the time of this writing (December 2016), farm gate* prices were relatively stable with 280-grade berries of both Ningxia and Qinghai origin selling at 45-46 Chinese Yuan Renminbi (CNY) per kg ($6.76-$6.91 per kg); 220-grade from Qinghai at 48-50 CNY per kg ($7.21-$7.51 per kg); and 220-grade from Ningxia at 55 CNY per kg ($8.26 per kg).⁹⁵ At the same time, the indicative market prices^† for 280-grade lycium berries ranged from 60-68 CNY per kg ($9.00-$10.21 per kg) at the major TCM markets in China.⁹⁶

The use of lycium fruit (or fruit extract) as an active ingredient of traditional Asian medicines and of herbal dietary supplements and functional foods has been increasing significantly over the past few years. Given that China is the top producer and exporter for the global market and that nearly half of the export volume is certified organic, there is evidence that sustainable agriculture and sustainable wild-collection standards are being implemented in order to satisfy the growing demand.

—Gayle Engels and Josef Brinckmann

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