Lycium

Lycium (Wolfberry / Goji Berry): A Comprehensive Reference

1. Identity and Botanical Classification

Lycium belongs to the Solanaceae family and is cultivated year-round in regions such as China, Japan, Korea, North America, Europe, and Central Asia. Out of the 97 Lycium genus species, 31 are used for both food and medicine. Commercially and pharmacologically, two species dominate: Lycium barbarum L. (Chinese wolfberry) and Lycium chinense Mill. (Chinese boxthorn). Only L. barbarum and L. chinense have been transformed into globally traded commodities.

Wolfberry (Lycium barbarum) was assigned by the Swedish botanist Carolus Linnaeus in 1753. He is responsible for the species name barbarum, while botanist Philip Miller described Lycium chinense just 15 years later.

Lycium barbarum (LB), also known as wolfberry and Goji berry, is a plant of the Solanaceae, mainly distributed in the Northwest of China, such as Ningxia, Qinghai, Shanxi, Xinjiang, and Inner Mongolia. It is a Solanaceous defoliated shrub; its fruits are 1–2 cm-long, bright orange–red ellipsoid berries.

The majority of commercially produced Lycium barbarum comes from the Ningxia Hui Autonomous Region in central North China and the Xinjiang Uyghur Autonomous Region in western China.

Common Names and Synonyms

• Lycium barbarum berries are also named wolfberry, Fructus lycii, and Goji berries.
• In China, the plant is called "Gouqizi." The name of the plant is gugija in Korea and kuko in Japan.
• The berry is also listed under its pharmacopoeial names Fructus Lycii (fruit) and Cortex Lycii Radicis (root bark).

Plant Parts Used

Three parts of the L. barbarum plant — fruits, leaves, and root barks — have been used as functional foods and traditional Chinese medicinal herbs in China for centuries and are now widely consumed all over the world. The berries (Fructus barbarum, Fructus lycii) are used for both food and medicine, whereas root bark (Cortex lycii radicis) is used solely for medicine.

Common Forms and Preparations

The berry is eaten raw, consumed in juice form, or added to tea or wine. The fruit is also processed to make tinctures, powders, and tablets. The fruits are dried with or without sulfur to yield the market herb, or the fresh fruits may be squeezed for their juice, which is then concentrated to preserve it for future use in making various beverages. Concentrated extracts and infusions prepared from the berries have a history of use as ingredients in various soft or alcoholic drinks marketed for their benefits to anti-aging, vision, kidney, and liver functions.

2. Traditional and Historical Use

China and East Asia

Lycium barbarum berries have been used in the People's Republic of China and other Asian countries for more than 2,000 years as a traditional medicinal herb and food supplement. In China, based on the name "枸杞," their use can be traced back over the last two millennia. Lycium fruits for anti-aging, improving eyesight, and nourishment were documented already in 500 C.E. (Mingyi Bielu).

Although lycium fruit was described in the Shennong Bencao Jing (ca. 100 A.D.), its use in traditional formulas was rather limited until the end of the Ming Dynasty period (1368–1644). At that time, it was frequently combined with tonic herbs such as rehmannia, cornus, cuscuta, and deer antler to treat a range of deficiency conditions.

Lycium barbarum has been used for more than 2,000 years in traditional Chinese medicine, with early records traced back to the Tang Dynasty. Currently, it is part of the Pharmacopoeia of the People's Republic of China.

In traditional Chinese medicine, Lycium barbarum can treat various diseases, including blurry vision, abdominal pain, infertility, dry cough, fatigue, dizziness, and headache. Meanwhile, Lycium barbarum has long been used in Oriental medicine as a potent anti-aging agent — for instance, it is considered effective for counteracting premature graying of hair.

Traditional System Classification

The first recorded use of lycium fruit as a medicinal herb is from the first century A.D. For thousands of years it has been used in China to promote a long, vigorous, and happy life. It is used as both a jing (yin) tonic for liver and kidney, and as a blood tonic.

On the basis of Chinese ethnobotanical knowledge, the traditional Chinese medicine "wolfberry" was used to nourish liver and kidney. In general, Lycium spp. have often been used for the treatments of blurry vision, fever, night sweat, kidney deficiency, cough and asthma, diabetes, heart diseases, gynecopathy, and neurasthenia.

Ethnic Uses Within China

In China, seven species and two varieties of the genus Lycium occur, of which four species have been used by different ethnic groups. Use records exist for twelve of the officially recognized 55 ethnic minorities of China. The whole plant has been used by the Miao and Yi for different purposes: Miao use it as a tonic, while Yi use it for sores and itching. The Yi and Dong use them differently — the fruits of L. chinense are for bleeding gums, while the whole plant is used as an antipruritic drug.

Contemporary Pharmacopoeial Status

Contemporary herbals such as the Zhonghua Bencao (1999), Xinbian Zhongyao Zhi (2002), and Zhongyao Da Cidian (2006) refer to both L. chinense and L. barbarum. Currently, it is part of the Pharmacopoeia of the People's Republic of China. The recommended dosage of dried berries varies between 5 and 12 g.

3. Key Constituents and Active Compounds

Overview of Phytochemical Profile

Lycium barbarum is rich in phytochemical compounds such as polysaccharides, carotenoids, organic acids, carbohydrates (fructose and glucose), phenolic compounds (such as phenolic acids and flavonoids), and vitamins (ascorbic acid). A total of 131 compounds have been identified via UPLC-HR-MS analysis, with 98, 28, and 35 constituents detected in fruits, leaves, and root barks respectively.

Lycium Barbarum Polysaccharides (LBPs)

L. barbarum polysaccharides (LBPs) are the primary active components of L. barbarum berries and have been reported to possess a wide array of pharmacological activities. LBPs are a major functional component of Lycium barbarum and contain several monosaccharides and 17 amino acids, including rhamnose (Rha), galactose (Gal), glucose (Glc), arabinose (Ara), mannose (Man), and xylose (Xyl). LBPs comprise 5–8% of the dried fruits.

Carotenoids: Zeaxanthin and β-Carotene

As to the seeds, they contain zeaxanthin (83%), β-cryptoxanthin (7%), β-carotene (0.9%), and mutatoxanthin (1.4%), as well as some minor carotenoids. Lycium barbarum carotenoids (LBCs) ranging from 0.03% to 0.5% dry weight are rich in zeaxanthin, β-carotene, lutein, and astaxanthin, with zeaxanthin being the predominant carotenoid, constituting 31–56% of the total carotenoid content.

The predominant carotenoid form found in the fruit is zeaxanthin dipalmitate. Zeaxanthin dipalmitate accounts for more than 56–75% of the total pigment content in the ripe fruits of L. barbarum. When ingested, zeaxanthin accumulates in fatty tissues, but especially in the macula, a region of the retina. It is believed that by having a good supply of this compound, the macula is protected from degeneration, which can be induced by excessive sun exposure (UV light) and by other oxidative processes.

Betaine

The Chinese Pharmacopoeia stipulates that Lycium barbarum contains not less than 0.3% of betaine. Betaine has been proven to have anti-aging effects and is an essential nutrient for humans. Betaine has been shown to reduce photodamage caused by UVB irradiation through the regulation of matrix metalloproteinase-9 activity in hairless mice.

Vitamins and Other Nutrients

Lycium barbarum contains abundant LBPs, betaine, phenolics, carotenoids (zeaxanthin and β-carotene), cerebroside, 2-O-β-d-glucopyranosyl-l-ascorbic acid (AA-2βG), β-sitosterol, flavonoids, and vitamins (in particular, riboflavin, thiamine, and ascorbic acid). The content of vitamin C (up to 42 mg/100 g) in wolfberry is comparable to that of fresh lemon fruits.

Leaves and Root Bark Constituents

Leaves of Lycium barbarum are a rich source of bioactive compounds; they contain polyphenols, flavonoids, alkaloids, minerals, and vitamins, and therefore exhibit antioxidant, enzyme inhibitor, antimicrobial, and antimutagenic activities.

4. Established Mechanisms of Action

Antioxidant Activity

The polysaccharides extracted from the fruits of Lycium barbarum exert their anti-aging effect through reducing oxidative stress, modulating the immune response, enhancing neuronal responses, and promoting cytoprotection. LBPs have been reported to mediate significant anti-aging effects through antioxidant, immunoregulative, and anti-apoptotic activities and by reducing DNA damage.

Immunomodulation

Published studies have associated LBP intake with a number of therapeutic effects, including anti-aging, metabolic effects, neuroprotective effects in neurodegeneration and neurotoxicity, including ocular neuroprotective effects. LBPs have been shown to stimulate lymphocyte proliferation and upregulate key cytokines. Several clinical studies in healthy subjects show that consumption of wolfberry juice improves general wellbeing and immune functions. LBPs are also reported to have antioxidative and anti-aging properties in different models.

Neuroprotection

The accumulation of excessive reactive oxygen species can exacerbate any injury of retinal tissue because free radicals can trigger lipid peroxidation, protein damage, and DNA fragmentation. Increased oxidative stress is associated with the common pathological process of many eye diseases, such as glaucoma, diabetic retinopathy, and ischemic optic neuropathy. LBPs counter these processes. LBP has been shown to have neuroprotective effects: it could not only improve the impairments of memory and neurogenesis in rats induced by scopolamine and reduce glutamate excitotoxicity in rat cortical neurons, but also enhance cellular immunity.

Metabolic and Antidiabetic Mechanisms

LBPs effectively reverted the inhibition of protein kinase B (AKT) and glycogen synthase 3 (GSK3) phosphorylation and countered the elevation of reactive oxygen species (ROS) in insulin-resistant HepG2 cells triggered by high glucose. Furthermore, LBP prevented the decline of glucose transporter isoform 2 (GLUT2) level in the diabetic mice liver and restored reduced glucose consumption and uptake. LBP also prevented the decrease in glycogen synthase (GYS2) mRNA expression and the reduction of liver glycogen content in diabetes mellitus mice.

Anti-inflammatory Mechanisms

LBPs inhibit the expression of phosphor-nuclear factors kappa B (NF-κB) and inhibitor kappa B alpha in kidney tissues. Collectively, LBPs possess antidiabetic and antinephritic effects related to NF-κB-mediated antioxidant and anti-inflammatory activities.

5. Scientific Evidence by Area of Use

5.1 Ocular Health and Neuroprotection of the Retina

This is the most extensively studied clinical area for Lycium barbarum. LBPs exert their anti-aging effect through reducing oxidative stress, modulating the immune response, enhancing neuronal responses, and promoting cytoprotection. The therapeutic efficacy of LBPs in preserving retinal ganglion cells and their functions has been demonstrated in a range of experimental models of optic neuropathies, including the acute and chronic ocular hypertension models, the partial optic nerve transection model, and the ischemic-reperfusion injuries model.

Preclinical Evidence (Animal/In Vitro): Research suggests that LBP may have a neuroprotective role to play in ocular diseases for which ischemia/reperfusion is a feature. Many studies have demonstrated that Lycium barbarum polysaccharides protect against oxidative injury in numerous cells and tissues.

Clinical Evidence: In a clinical trial with patients who had retinitis pigmentosa, daily consumption of Lycium barbarum granules showed neuroprotective effects, improving the outcome for the patients in terms of visual acuity, visual fields, and electroretinograms.

Available data indicate that antioxidant, immunomodulatory, and metabolic effects are predominantly supported by experimental studies, while human evidence is most consistent for ocular health outcomes, including plasma zeaxanthin levels and macular characteristics. Overall, evidence for retinal protection is promising but still largely preclinical.

5.2 Immune Function

Clinical Evidence (RCTs): To examine the systematic effects of L. barbarum on immune function, general well-being, and safety, researchers tested the effects of a standardized L. barbarum fruit juice (GoChi) at 120 mL/day, equivalent to at least 150 g of fresh fruit, or placebo for 30 days in a randomized, double-blind, placebo-controlled clinical study in 60 older healthy adults (55–72 years old). The GoChi group showed a statistically significant increase in the number of lymphocytes and levels of interleukin-2 and immunoglobulin G compared to pre-intervention and the placebo group, whereas the number of CD4, CD8, and natural killer cells or levels of interleukin-4 and immunoglobulin A were not significantly altered.

A separate RCT evaluated a milk-based wolfberry formulation. After an earlier report showing that a proprietary milk-based wolfberry formulation (Lacto-Wolfberry) enhances in vivo antigen-specific adaptive immune responses in aged mice, a subsequent study demonstrated the effect of dietary Lacto-Wolfberry supplementation on immune functions in the elderly, especially vaccine response. A 3-month randomized, double-blinded, placebo-controlled study was conducted on 150 healthy community-dwelling Chinese elderly (65–70 years old) supplemented with Lacto-Wolfberry or placebo (13.7 grams/day). Immune response to influenza vaccine was assessed in the study, along with inflammatory and physical status. Elderly persons who consumed Lacto-Wolfberry for 3 months showed higher serum influenza-specific IgG concentrations and seroconversion rate after receiving an influenza vaccine.

Evidence Strength: Positive findings from small-to-moderate RCTs exist in this domain; however, sample sizes remain limited and replication is needed.

5.3 General Well-Being and Antioxidant Status

A randomized, double-blind, placebo-controlled clinical trial — the first study reported from outside China examining the general effects of the orally consumed goji berry as a standardized juice (GoChi) in healthy adults for 14 days — examined by questionnaire subjective ratings (0–5) of general feelings of well-being, neurologic/psychologic traits, gastrointestinal, musculoskeletal, and cardiovascular complaints, as well as any adverse effects. Results clearly indicated that daily consumption of GoChi for 14 days increases subjective feelings of general well-being, and improves neurologic/psychologic performance and gastrointestinal functions.

A 2021 RCT specifically investigated oxidative stress. A 16-week, parallel design randomized controlled trial aimed to investigate the impact of adhering to a healthy dietary pattern, either with or without whole dried wolfberry (15 g/d), on oxidative stress status (plasma malondialdehyde and 8-iso-prostaglandin F2α) in middle-aged and older adults. Plasma 8-iso-prostaglandin F2α, plasma zeaxanthin, and skin carotenoids status were significantly raised in the wolfberry consuming group (n = 22; p < 0.05) compared to the control group, which showed no changes (n = 18).

Evidence Strength: Modest RCT evidence exists demonstrating changes in antioxidant biomarkers and subjective well-being, though some trials are small, industry-sponsored, and short in duration.

5.4 Metabolic Health: Blood Glucose and Lipids

Blood Glucose (Clinical Evidence): A double-blinded, placebo-controlled RCT on 67 patients with type 2 diabetes mellitus compared blood glucose and lipid levels of patients given 300 mg/day LBP treatment perorally compared to type 2 diabetic controls. At 3 months, patients on LBP treatment had significant increases in high-density lipoproteins (HDL) levels from baseline compared to controls.

Lipid Profiles (Systematic Review): A systematic review and meta-analysis showed that L. barbarum supplementation might have some beneficial effects on triglyceride (TG) and HDL-C concentrations in adults, and that L. barbarum fruit has an even greater effect on TG and HDL-C concentrations. Considering the sensitivity analyses and limitations of the studies included, further large-scale studies are needed to confirm these findings.

Evidence Strength: There is an evident lack of well-designed randomized control trials to evaluate the effect of LBP in humans. Though there are published RCTs for investigating its effect in diabetes and diabetic retinopathy, the respective sample sizes of the studies are insufficient for the results to have significant impact in clinical management. Evidence remains preliminary.

5.5 Neuroprotection: Alzheimer's Disease and Neurodegeneration

Preclinical Evidence: Lycium barbarum extracts (LBE) have been demonstrated to be neuroprotective in various animal models of neurodegeneration. In an AD mouse model, LB increased horizontal and vertical movement in the autonomic activity test, improved endurance time in the rotarod test, and decreased escape latency time in the Morris water maze test. Additionally, the levels of acetylcholine and choline acetyltransferase were significantly increased in the serum and hypothalamus in the LB-treated AD mice. These data suggested that LB may exert neuroprotective effects and may aid in preventing neurodegenerative disease.

One study aimed to investigate whether extracts from L. barbarum have neuroprotective effects against toxicity of fibrillar Aβ(1–42) and Aβ(25–35) fragments. Primary rat cortical neurons exposed to Aβ peptides resulted in apoptosis and necrosis. Pre-treatment with extract isolated from L. barbarum significantly reduced the release of lactate dehydrogenase (LDH). In addition, it attenuated Aβ peptide-activated caspases-3-like activity.

Findings from a 5xFAD transgenic mouse study suggest that LBE treatment can enhance neuroplasticity, reduce systemic inflammation, and improve phagocyte clearance of Aβ deposition via inducing a neuroprotective microglial phenotype throughout the central nervous system.

Evidence Strength: Evidence for neuroprotection in Alzheimer's disease is exclusively from animal and cell models as of the available literature. No human clinical trials have evaluated this specific application.

5.6 Anti-Cancer and Antitumor Activity

LBPs show antitumor activities against various types of cancer cells and inhibit tumor growth in nude mice through induction of apoptosis and cell cycle arrest. There is good evidence from existing studies on the antifibrotic, antioxidizing, neuroprotective, anticancer, and anti-inflammatory effects of LBPs.

Evidence Strength: Antitumor findings are based on in vitro and in vivo (animal) models only. No human clinical trial data specifically evaluating LBPs against cancer has been confirmed in the sources reviewed. This area remains preclinical.

5.7 Cardiovascular Health

In a 16-week, parallel design, randomized controlled trial, middle-aged and older adults (n = 41) were provided dietary counseling and assigned to either consume or not consume 15 g of wolfberry daily. At baseline and post-intervention, plasma lipidomics was assayed and its relationships with classical CVD risk factors, vascular health, oxidant burden, carotenoids status, body composition, and anthropometry were examined. Characteristic alterations to the plasma lipidome were observed with healthy dietary pattern adherence and wolfberry consumption. An examination of these fluctuations suggests potential biochemical mechanisms that may mediate the antioxidant and cardiovascular protective effects of healthy dietary pattern adherence and wolfberry intake.

Evidence Strength: RCT evidence suggests possible lipid profile modulation, but studies are small and confounded by simultaneous healthy diet interventions. Results are exploratory.

6. Body Systems and Health Areas Associated with Lycium

Biological activities assessed in the scientific literature include antioxidant, immunomodulatory, anti-inflammatory, hepatoprotective, neuroprotective, anti-obesity, anti-hyperglycemic, hypertension and heart protective, hepatoprotective, anti-fatigue, and other relevant pharmacological effects, supported by in vitro, in vivo, and clinical evidence.

• Visual System / Ophthalmology: LBPs have strong biological activities, including immune regulation, antioxidation, and neuroprotection, and have been shown to improve vision in numerous studies. The key mechanism is via zeaxanthin accumulation in the macula and LBP-mediated protection of retinal ganglion cells.
• Nervous System: The neuroprotective effects of LBP are some of the most widely studied fields regarding LBP's therapeutic effects.
• Immune System: LBPs have demonstrated the ability to upregulate lymphocyte counts and interleukin-2 in human RCTs, and to enhance vaccine responses in the elderly.
• Metabolic / Endocrine System: Evidence from animal studies and small RCTs suggests effects on blood glucose homeostasis, insulin sensitivity, and lipid profiles.
• Liver: Traditional Chinese medicine used wolfberry to nourish liver and kidney. Lycium barbarum exhibits immune-enhancing, hepatoprotective, and neuroprotective properties.
• Renal System: LBPs inhibit albuminuria and blood urea nitrogen concentration and serum levels of inflammatory factors, indicating protective action on renal tissue.
• Reproductive System: Lycium barbarum has long been well-known as a traditional Chinese medicine that promotes health and longevity. Studies have shown that LBPs possess multiple pharmacological functions, including immunomodulatory, antioxidant, hypolipidemic, anti-tumor, and anti-aging functions. Animal research has further explored protective effects on spermatogenic function under diabetic conditions.
• Skin: Betaine and LBPs have demonstrated in vitro and animal-model protection against UVB-induced photodamage.

7. Dosage Forms and Dosages Reported in Studies

Dosages vary considerably by preparation type, study population, and clinical target. The following are dosages as explicitly reported in sources:

• Traditional (dried berries, TCM): The recommended dosage of dried berries varies between 5 and 12 g.
• Dried fruit (traditional/functional food): The dried fruit is administered with other herbs or consumed alone with hot water, at a dose varying between 6 and 18 g.
• Standardized juice (GoChi, immune/well-being RCTs): 120 mL/day, equivalent to at least 150 g of fresh fruit, for 30 days in a randomized, double-blind, placebo-controlled clinical study in 60 older healthy adults (55–72 years old).
• GoChi juice (general well-being RCT): 120 mL of GoChi per day or placebo, with measures of body weight, BMI, blood pressure, pulse rate, and visual acuity assessed before and after.
• LBP extract (diabetes RCT): 300 mg/day LBP treatment perorally in 67 patients with type 2 diabetes mellitus for 3 months.
• Lacto-Wolfberry formulation (elderly immune RCT): 13.7 grams/day for 3 months in 150 healthy community-dwelling Chinese elderly (65–70 years old).
• Whole dried wolfberry (oxidative stress RCT): 15 g/day for 16 weeks in middle-aged and older adults.
• LBP (animal AD model): Orally administered LBP at 150 and 300 mg/kg once a day in an Alzheimer's disease rat model.
• LBE (animal AD/retinal model): 3xTg-AD mice were fed with low (200 mg/kg) or high (2 g/kg) dose hydrophilic LBE daily for 2 months.

Note on forms: Due to some limitations such as poor bioavailability and instability, encapsulation via spray drying with polymeric carriers provides a practical strategy to improve the stability, bioavailability, and applicability of goji berry bioactives in the health sector.

8. Safety Considerations and Drug Interactions

General Safety Profile

The injection of 2.4 g/kg of L. barbarum fruit extract did not cause adverse reactions; the LD50 by injection was determined to be about 8.3 g/kg. Although no adverse effects of LBP have been demonstrated until now, there is little scientific evidence about its toxicological effects in humans.

Drug Interaction: Warfarin (Anticoagulants)

The most clinically significant documented interaction involves the anticoagulant warfarin. Multiple published case reports describe a pattern of elevated International Normalized Ratio (INR) in warfarin-stabilized patients consuming Lycium barbarum preparations:

• An elevated INR of 4.1 was observed in a 61-year-old Chinese woman previously stabilized on anticoagulation therapy (INR 2–3), with no changes in her other medications or lifestyle. A review of her dietary habits revealed four days of drinking a concentrated Chinese herbal tea made from Lycium barbarum fruits (3–4 glasses daily) prior to her clinic visit.
• An 80-year-old Chinese woman on a chronic stable dose of warfarin experienced two episodes of an elevated INR after drinking herbal tea containing Lycium barbarum L.
• A 65-year-old Chinese man taking a prolonged maintenance dose of warfarin experienced an elevated INR with associated bleeding after drinking Gouqizi (goji berry) wine. The report illustrates that large doses (more than 6–12 g) of Gouqizi can significantly enhance the anticoagulant action of warfarin and may cause similar adverse effects.
• A markedly elevated INR was observed in a 71-year-old Ecuadorean-American woman hospitalized following the consumption of Himalayan Goji Juice. She described symptoms of epistaxis, bruising, and rectal bleeding. Following discontinuation of the goji juice, warfarin, and the administration of phytonadione, her INR decreased from a markedly elevated, indeterminate level (prothrombin time greater than 120 seconds) to 2.6 over two days.

Application of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's elevated INR with associated bleeding and her concomitant use of L. barbarum and warfarin.

The proposed mechanism has been investigated. An in vitro study noted that Lycium barbarum tea inhibited warfarin metabolism by weakly inhibiting CYP2C9 activity in human liver microsomes, suggesting that this interaction may be due to the effect of factors such as absorption, P-glycoprotein, or the anticoagulant effect of the herb itself. It was also observed that it was possible that the metabolites of Lycium barbarum displaced warfarin from its plasma protein binding site, leading to an increase in INR.

Given the high frequency of use of L. barbarum fruit and of warfarin, the lack of more reports of interaction suggests that the incidence may be very low. Nevertheless, two other published reports had previously described similar interactions between warfarin and a tea containing L. barbarum. Patients should be educated about avoiding popular herbal drinks, such as goji juice, that contain L. barbarum while they are taking warfarin.

Evidence Gaps and Research Limitations

Among the publications in one systematic review, only 2 were clinical studies, with both being double-blinded placebo-controlled randomized control trials. Of the remaining 18 laboratory-based studies, 11 were in vivo studies, 5 were in vitro studies, and 1 study had both in vivo and in vitro results. As the studies were diverse in their study designs and outcomes, the results could not be combined for meta-analysis.

Overall, from existing data, there is an evident lack of well-designed randomized control trials to evaluate the effect of LBP in humans. Though there are published RCTs for investigating its effect in diabetes and diabetic retinopathy, the respective sample sizes of the studies are insufficient for the results to have significant impact in clinical management. Nevertheless, the promising findings identified from both clinical studies and translational work should warrant greater interest in this field of research.

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