With about 750 species, the genus Ficus, which belongs to the mulberry family (Moraceae), is one of the largest genera of flowering plants.1,2 The Transcaucasia region (Armenia, Azerbaijan, Georgia, Iran, and Turkey) has been suggested as one of the centers of origin and diversity of the species.3 Wild fig (F. carica) trees are widespread and considered to be native to parts of southern Asia (Iran), western Asia (Armenia, Azerbaijan, Georgia, and Turkey), and central Asia (Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan).4 Two subspecies, F. carica subsp. carica and F. carica subsp. rupestris, are specifically reported to occur in both Iran5 and Turkey.6
There are four fig cultivar-types — Common, Smyrna, San Pedro, and Caprifig3 — and due to the long history of fig cultivation, hundreds of cultivars exist within these four types.7 There are also hundreds of genotypes (figs of different genetic composition).8 Each cultivar can include multiple genotypes. Several Caprifig (F. carica var. caprificus) cultivars are commonly grown in the eastern Mediterranean region of Turkey.9 Nearly all fig trees cultivated in Fars province, Iran, are the Sabz cultivar, a Smyrna cultivar-type.10
The fruit sac of the fig is a type of inflorescence or, in pomological terms, a “syconium,” a fleshy, hollow receptacle in which pistils can accommodate either a wasp egg until it hatches or fig seeds.1 Due to significant polymorphism, figs exhibit diverse morphological characteristics and ecological adaptations.11 Providing a general description of F. carica is difficult, as the color, shape, and size of plant parts vary considerably among the many different types. The Pharmacopoeia Helvetica describes “Caricae fructus” as the dried, whole infructescence (fruiting stage of an inflorescence) of F. carica, containing a minimum of 45% extractive matter.12 For the purposes of this article, this syconium will generally be referred to as the “fruit” of the plant.
An extraordinary mutualism (mutual dependence for survival) exists between figs and their pollinating wasps. This fig-wasp interaction has been ongoing for more than 80 million years.13 Ficus carica fruits are pollinated exclusively by the female fig wasp (Blastophaga psenes, Agaonidae) that enters the fig through the ostiole (the small opening of the involuted fig inflorescence) to oviposit (lay eggs).
The fig tree is gynodioecious (having female flowers on one tree and hermaphrodite flowers on another) and functionally dioecious (male and female flowers occur on separate trees).9 Female fig trees have long-styled female flowers that do not host wasp larvae. This fruit produces seeds but no pollen. Male fig trees have short-styled female flowers that host wasp larvae but produce very few seeds. Figs from functionally male trees produce pollen and also harbor wasps (pollen vectors). When a wasp emerges from a fig cavity, dusted with pollen, it has about one day to find and enter a receptive fig (on male or female trees) in its short lifespan outside of figs.14
A recent study that investigated the traditional knowledge of wild edible plants used by indigenous people in Yeşilli (Mardin province in southeastern Turkey) found F. carica subsp. carica to be among the most culturally important taxa.15 Fig fruit is also one of Turkey’s leading export crops. Its largest fig tree populations are found on the shores of the Black Sea, Marmara Sea, and Aegean Sea in the Mediterranean region, and along rivers in southeastern and central Anatolia. Wild fig trees also are found in valleys in the provinces of Siirt, Diyarbakır, Gaziantep (southeastern Anatolia), and Elazığ (eastern Anatolia), and on Ahır Mountain in Kahramanmaraş province (Mediterranean region).6 Furthermore, Turkey is, by far, the world’s leading producer and exporter of figs, having exported nearly 85,000 metric tons in 2019.16 The United States imported 15,049 metric tons of figs and fig products in 2019, mainly from Turkey, with relatively smaller amounts brought in from Greece, Mexico, Spain, Italy, and a few other countries.17 Although the United States does not import figs from Iran at this time, Iran is also a major fig producer and exporter to the global market. About 90% of Iranian dried figs are produced in Fars province.10
Figs have a considerable food-medicine overlap based on traditional uses.18 Ficus carica fruit is used as a medicinal ingredient of formulations, particularly in the Unani system of medicine,19 but its therapeutic uses also are documented in both folk and traditional European herbal medicines,12 as well as in Iranian traditional medicine. Other Ficus species and plant parts also are used medicinally. For example, the bark of F. religiosa and the fruit of F. glomerata and F. hispida are used in the Indian systems of medicine. However, this article concerns mainly the fruit of F. carica.
HISTORY AND CULTURAL SIGNIFICANCE
According to a passage in the Book of Genesis of the Bible, after eating the forbidden fruit, Adam and Eve realized that they were naked and quickly covered themselves in fig leaves. Later on, the Book of Deuteronomy says that God gave the Hebrews a land rich in figs.20 The biblical fig, however, was likely not F. carica, but rather the sycamore fig (F. sycomorus).18
In his 1737 work Genera Plantarum, Swedish botanist Carl Linnaeus (1707-1778) assigned the genus name Ficus.21 In the 1759 edition of Systema Naturae, Linnaeus named eight Ficus species, including carica.22 The Latin genus name Ficus, meaning fig tree, is the origin of the various European common names such as fica (Italian), figo (Portuguese), higo (Spanish), figue (French), Feige (German), vijg (Dutch), and fig (English).20 The species name carica stems from the Latin term caricus, meaning a fig “from Caria,” a region of western Anatolia, also known as Asia Minor or Asian Turkey.23 In the fourth century BCE, philosopher Theophrastus (ca. 371–287 BCE) reportedly stated that most of the “good” fruits, such as the fig, had already been named.24
The earliest evidence of human consumption of figs comes from Pre-Pottery Neolithic A sites (ca. 10,000–8,800 BCE) from the Jordan Valley to the Upper Euphrates (mountains of southeastern Turkey). It is not certain whether figs at this time were entirely wild or if domestication had begun.25 In any case, F. carica is likely one of the oldest food and medicine tree crops domesticated and used by humans.18 While some archaeological evidence suggests that it has been cultivated for more than 11,000 years, possibly predating cereal grains,26 this has been disputed by other Ficus experts.27
In the basalt desert of present-day Jordan, charcoal from fireplaces at an excavated late Neolithic site (dated to roughly 6490–6235 BCE) in Wadi Qattafi, contains evidence of F. carica trees. As the fig tree is hygrophilous (i.e., it grows in damp conditions), its occurrence here suggests that a wetter and more tree-covered ecosystem existed previously, as opposed to its present-day arid zone condition.28 There is evidence of Levantine-Aegean trade in F. carica in the Late Bronze Age. Excavations of the Uluburun shipwreck off the Mediterranean coast of what is now Kaş, Turkey, which has been dated to about 1350–1300 BCE, uncovered fruit cargo of figs, grapes (Vitis vinifera, Vitaceae), olives (Olea europaea, Oleaceae), and pomegranates (Punica granatum, Lythraceae), among other fruits and nuts.29
Another excavation in Jordan known as Tell Dhiban (12 miles east of the Dead Sea) identified fig remains common to both the Iron Age (ca. 1200–500 BCE) and Middle Islamic period (ca. mid-ninth to 15th centuries CE).30 Some of the earliest evidence of fig trees in Jerusalem is provided by fig leaf imprints on sherds (fragments of pottery) dated to the Late Hellenistic period (second to first centuries BCE), uncovered from the Giv’ati Parking Lot, Tyropoeon Valley, west of the entrance to the City of David.31 Plates of whole figs, which were presumably waiting to be eaten, are among the carbonized plants recovered from sites in Pompeii that were preserved after the volcanic eruption of Mount Vesuvius in 79 CE.32
In the first century CE, naturalist Pliny the Elder (23 or 24–79) listed 29 varieties, with information on the locations where each was grown.24 Ficus carica is among the most cited taxa in a study of iatrosophia, a type of Greek medical handbook of Byzantine (330-1453) origin. The study found links between the iatrosophia text and current medicinal plant usage in Greek Orthodox monasteries on Cyprus.33 The medical use of figs in Bulgaria for cough is documented in a canon written in the Old Church Slavonic language by St. Ivan Rilski (876-946), Bulgaria’s first hermit.34,35 Fig trees reportedly were introduced to England around 1440. This may explain why fig seeds were found in abundance in the top layer of an archaeological excavation of a medieval sewer in the port city of Plymouth in southwestern England.36 In several medical formulations described in the Chilandar Medical Codex, considered to be the most significant medieval Serbian pharmacological manuscript on European medical science from the 12th to 16th centuries, F. carica fruit was described as having actions including purgative, expectorant, anthelmintic, antidepressant, tonic, and cold prevention.37
Traditional Medicinal Uses
In Fars province, Iran, figs traditionally are used as a purgative and for warts.38 In Omani traditional medicine, fig fruit, boiled in water, is drunk to relieve cough.39 In Greek folk medicine, the eating of large quantities of figs is said to expel intestinal worms.40 In the folk medicine of Montecorvino Rovella (inland Campania, Italy) an aqueous decoction, drunk as an antitussive, is prepared with dried fig, apple (Malus pumila, Rosaceae) fruit, sour cherry (Prunus cerasus, Rosaceae) fruit, almond (P. dulcis) epicarp (outer skin of the fruit) and maidenhair fern (Adiantum capillus-veneris, Pteridaceae) leaf, with honey (produced by Western honeybees, Apis mellifera, Apidae) added.41 On islands of Croatia in the Adriatic Sea, rakija travarica, a common traditional alcoholic beverage, is made from grape pomace distillate with figs and fennel (Foeniculum vulgare, Apiaceae) aerial parts, sage (Salvia officinalis, Lamiaceae) leaf, cade juniper (Juniperus oxycedrus, Cupressaceae) pseudo-fruit, carob (Ceratonia siliqua, Fabaceae) fruit, and wormwood (Artemisia absinthium, Asteraceae) flowering tops, among other local herbs.42
Fig fruit was included on the primary list of materia medica of the first edition of the Pharmacopoeia of the United States of America (USP 1820) and was included as a component of several preparations including “Confection of Senna,” also called “Lenitive Electuary,” for constipation, made from senna (Senna alexandrina, Fabaceae) leaf, coriander (Coriandrum sativum, Apiaceae) fruit, licorice (Glycyrrhiza glabra, Fabaceae) root, fig fruit, prune (Prunus domestica, Rosaceae) fruit, tamarind (Tamarindus indica, Fabaceae) fruit pulp, and refined sugar (made from Saccharum officinarum, Poaceae).43 The medical uses and properties of Caricae fructus USP were described in the corresponding first edition of the Dispensatory of the United States of America (USD 1833):
Figs are nutritious, laxative, and demulcent. In the fresh state, they are considered in the countries where they grow a wholesome and agreeable aliment. As we obtain them, they are apt, when eaten freely, to produce flatulence, pain in the bowels, and diarrhoea. Their chief medical use is as a laxative article of diet in cases of constipation. They occasionally enter into demulcent decoctions; and when roasted or boiled, and split open, may be applied as a suppurative cataplasm to parts upon which an ordinary poultice cannot be conveniently retained.44
Figs were dismissed from the ninth decennial revision of the US Pharmacopoeia (USP IX 1910).45 As a result, the monographs Ficus USP VIII and Compound Syrup of Figs (Syrupus Ficorum Compositus) entered the fourth edition of The National Formulary (NF IV 1916).46 When an article was dismissed from the USP, it was generally admitted to the next edition of the NF.47 The status of fig as an official compendial article in the United States, however, came to an end when it was dismissed from the sixth edition of The National Formulary (NF VI 1936). In 1948, the US Federal Trade Commission (FTC) issued a cease-and-desist order to Universal Laboratories (Dallas, Texas) to stop advertising its product Syrup of Figs in ways that imply that fig fruit was the active ingredient responsible for the laxative effect. According to the FTC order, the fig content of the product had no therapeutic value, and the laxative effect was provided by other active ingredients.48
Although there were quality standards monographs for dried ripe figs as well as compound fig syrup (with senna pods) in the 1948 supplement to the sixth edition of the German Pharmacopoeia (DAB Erg.-B.6),49 these were omitted from the seventh editions of the pharmacopeias of both former West Germany (DAB 7 1968) and former East Germany (DAB 7-DDR 1973).50 At the same time, however, versions of these monographs entered the sixth edition of the Pharmacopoeia Helvetica (PhHelv VI 1971) and remain official in the currently valid 11th edition (PhHelv XI 2019).12 In 1990, the German Commission E published a negative monograph for use of Caricae fructus (dried fruit of F. carica), as well as preparations thereof, as a laxative drug for constipation, stating that the claimed efficacy had not yet been sufficiently documented.51 The US Department of Agriculture (USDA) established the “United States Standards for Dried Figs” in 2001.52 In 2007, a monograph for “Anjeer fruit” (dried fleshy receptacles/fruits of F. carica) entered volume II of the Unani Pharmacopoeia of India.19
CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES
In the United States, figs are used mainly as conventional food. USDA quality standards define US Grade A, US Grade B, and Substandard (the quality of dried figs that fails to meet the requirements of US Grade B).52 The US Food and Drug Administration (FDA) also provides specifications for canned figs in the Code of Federal Regulations (21CFR Part 145).53 An independent Generally Recognized as Safe (GRAS) conclusion dossier (formerly called GRAS Self-Determination or Self-Affirmed GRAS) has been prepared for a specific branded abscisic acid (ABA)-enriched fig fruit extract (ABAlife®; Euromed, Spain). Nearly 70 fig-containing products are listed in the US National Institutes of Health’s (NIH’s) Dietary Supplement Label Database. The listed dietary supplement products contain fig ingredients in various forms including concentrate, extract, fruit powder, juice powder, and syrup.54
In Canada, in addition to use as a conventional food, fig fruit may also be used as an active ingredient of licensed natural health products (NHPs), which require pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD).55 Licensed NHPs that contain a fig preparation equivalent to 20 grams of dried figs or 100 grams of fresh figs may be labeled with claim statement(s) to the effect of “Provides antioxidants that help protect against cell damage caused by free radicals.”56 Certain fig ingredients also are permitted for use as non-medicinal components of licensed NHPs. For example, fig fruit extract may be used as a skin-conditioning agent in topical NHPs, fig juice concentrate may be used as a color additive, natural flavor enhancer, or sweetener of orally ingested NHPs, and fig juice powder may be used as a cosmetic astringent.55
In the European Union (EU), F. carica fruit powder is authorized for use as a skin-conditioning component of cosmetic products. Extract of the fruit is authorized for use as a humectant (a substance that holds and retains moisture), fruit juice as an astringent ingredient, and fig fruit water (aqueous solution of the steam distillate obtained from the fruit) for masking function (to reduce or inhibit the basic odor or taste of the cosmetic product).57 Ficus carica fruit and other plant parts are also included on the BELFRIT (Belgium, France, and Italy) list of plants that are eligible for use in food supplements in the EU.58 And, as permitted under Article 13.1 of the European Commission regulation on nutrition and health claims, several general function claims have been proposed for F. carica fruit and leaf preparations.59 Regarding proposed antioxidant health claims, in 2010, the European Food Safety Authority (EFSA) issued an opinion that no evidence had been provided to establish that having antioxidant activity, content, and/or properties is a beneficial physiological effect.60 EFSA opinions on other proposed claims are pending.
In 2014, the German Federal Office of Consumer Protection and Food Safety (BVL) assessed and classified F. carica fruit as a common food without any known use as a medicinal product.61 In Switzerland, “Caricae sirupus compositus” (compound fig syrup) is an official compendial article prepared from figs (Caricae fructus) in combination with senna pods (Sennae fructus) and non-active ingredients sucrose (Saccharum liquidum), ethanol (Ethanolum 96 per centum), peppermint (Mentha × piperita, Lamiaceae) aerial parts essential oil (Menthae piperitae aetheroleum), clove (Syzygium aromaticum, Myrtaceae) flower bud essential oil (Caryophylli floris aetheroleum), methyl-4-hydroxybenzoate (Methylis parahydroxybenzoas), propyl-4-hydroxybenzoate (Propylis parahydroxybenzoas), and purified water (Aqua purificata).12
In countries where the Unani system of medicine is recognized and practiced (e.g., Bangladesh, India, Malaysia, Pakistan, and Sri Lanka), dried ripe figs are used as a component of formulations for treating patients with conditions including splenitis (inflammation of the spleen), epilepsy, and asthma.19
Though fig is well-established as a traditional medicine and ingredient in dietary supplements, pre-clinical and clinical research that validates traditional uses is relatively scant.62,63 The phytochemistry of fig fruit is complex due to the variety of compounds in the epidermis and pulp. The most prominent compounds include phenols and anthocyanins (Table 1), as well as carotenoids such as lutein, b-carotene, a-carotene, cryptoxanthin, lycopene, and zeaxanthin.64
Laboratory and Animal Studies
Alamgeer et al (2017) investigated the hypotensive activity of an aqueous methanolic extract of fig fruit in rats, as well as effects on heart rate and force of contraction.65 The extract caused a significant decrease in blood pressure, negative inotropic effects (weakening the force of muscular contractions), and chronotropic effects (changing heart rate), but it did not block the stimulatory effects of adrenaline or calcium chloride. The authors attributed these effects to the presence of flavonoids, phenols, and potassium and concluded that fig may reduce heart disease risk in hypertensive subjects and may affect coronary ischemia and reperfusion injury. Debib et al (2016) studied the effects of phenolic fractions of fig fruit and olive oil on carbon tetrachloride (CCl4)-induced hepatotoxicity in male Wistar rats. The fractions significantly prevented CCl4-induced increases in levels of glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and alkaline phosphatase, with a methanolic extract of dried fig being more hepatoprotective than dried fig itself.66 Alsahli et al (2019) also investigated the protective effect of a fig extract (exact composition not described) on CCl4-induced hepatotoxicity in mice. The fig extract significantly restored alterations in liver enzymes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, and reduced inflammation and blood vessel dilation caused by CCl4 induction.67 Kore et al (2011) demonstrated nephroprotective effects of an aqueous-ethanolic fig extract through normalizing elevated levels of malondialdehyde in gentamicin-induced nephrotoxicity in rats.68
Gilani et al (2008) attempted to establish the pharmacological basis for the traditional use of fig in inflammatory and spasmodic disorders. They investigated an aqueous-ethanolic fig extract for antispasmodic effects in isolated rabbit jejunum preparations and antiplatelet effects in an ex vivo model of human platelets.69 Results showed that spasmolytic and antiplatelet activities are likely mediated through the activation of adenosine triphosphate (ATP)-sensitive potassium channels. Oh et al (2011) investigated the laxative effects of figs in a beagle model of constipation induced by a high-protein diet and movement restriction. Administration of fig paste significantly decreased segmental colonic transit time and increased stool weight.70 Lee et al (2012) examined the effects of fig paste in loperamide-induced constipation in a rat model. Fig paste improved fecal pellet number, weight, water content, thickness, and mucin areas in the distal colon.71 Rtibi et al (2018) studied the effect of a fig aqueous extract on delayed gastric emptying and motility disturbances in dextran sulfate sodium-induced acute colitis in rats. The fig extract significantly reduced the severity of constipation and improved gastrointestinal transit, gastric emptying, and fecal parameters. The effects were attributed to the presence of carbohydrates, polysaccharides, phenolic acids, and flavonoids in the fig extract.72
The role of Ficus species in the management of diabetes was reviewed by Deepa et al (2018). They attribute significant enhancement of insulin secretion and subsequent reduction of blood glucose in various in vivo studies to bioactive metabolites such as flavonoids, phenolic acids, tannins, and vitamin E, among others.73 El-Shobaki et al (2010) studied the effects of fig fruit on glucose and lipid concentrations in alloxan-induced diabetic rats. Treatment lowered blood sugar and significantly ameliorated hypercholesterolemia and hyperlipidemia. These results were attributed to the anti-inflammatory and antioxidative effects of fig’s polyphenols.74 Belguith-Hadriche et al (2016) elucidated hypolipidemic and antioxidant effects of phenolic constituents of an aqueous-ethanolic fig extract. The fig extract improved the lipid profile (decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol). It also reduced thiobarbituric acid reactive substances and increased antioxidant enzymes in liver, heart, and kidney tissues of high-fat-diet-induced hyperlipidemic rats.75 This effect may be due to phenolic constituents, specifically vitexin, 2,5-dihydroxybenzoic acid, and rutin.
Gul et al (2018) demonstrated anxiolytic and antidepressant effects of a fig dilution (pulp diluted with water) similar to alprazolam in Swiss mice at 500 mg/kg/100 mL of water using forced swim test, elevated plus maze, and hole-board apparatus models.76 Alharthy and Bawazir (2019) investigated whether a mixture of fig and olive oil would delay cholinergic abnormalities and reduce oxidative stress in male albino rats with scopolamine-induced amnesia as a model of Alzheimer’s disease.77 They found that consumption of dried fig and olive oil resulted in a significant decrease in acetylcholinesterase levels in the hippocampus as well as an enhancement of behavioral activities, suggesting that these typical components of the Mediterranean diet may delay the progression of Alzheimer’s disease. However, these results need to be confirmed in human studies.
Researchers at the NIMML Institute and BioTherapeutics have characterized how ABAlife increases muscle metabolism, promotes glucose tolerance and insulin sensitivity, and decreases obesity-related systemic inflammation in a mouse model of obesity.78
Atkinson et al (2019) demonstrated significant effects of two versions of a fig fruit extract (ABAlife; the first version was standardized to contain ≥ 300 ppm ABA, and the second contained ≥ 50 ppm ABA) on postprandial glycemic and insulinemic responses in a randomized, double-blind crossover study with 10 healthy adults consuming four test beverages containing 100, 200, 600, and 1,200 mg of extract, respectively.79 Postprandial glucose and insulin were assessed at regular intervals over two hours. A significant reduction of the glycemic index was observed with only the two higher doses, whereas the insulinemic index was found to be significantly reduced at all doses in a dose-dependent manner. The authors recommend fig paste extract as an adjuvant treatment for glycemic management of chronic metabolic disorders.
Sardari et al (2015) evaluated the efficacy of fig paste (composition of investigational product not defined in congress abstract) in patients with multiple sclerosis-associated constipation in a two-arm, double-blind, randomized, placebo-controlled trial. Forty patients were assigned to receive either 10 g of fig paste (n = 20) or placebo (n = 20) three times daily for three months. Patients in the fig paste group experienced a significant reduction in the frequency of spontaneous bowel movements, straining during defecation, sensation of incomplete evacuation, and need for manual maneuvers to facilitate defecation.80
Tofighi et al (2017) studied the efficacy of a fig-flaxseed (Linum usitatissimum, Linaceae) combination (0.31 g of flaxseed powder and 1.26 g of unspecified fig extract per caplet) in a 14-day pilot study with 15 patients with functional constipation meeting Rome III criteria. Patients took three caplets daily and recorded bowel activities. Frequency of defecation, frequency of retentive posturing, frequency of large fecal mass, pain during evacuation, and consistency of stool all improved significantly. Clinical parameters remained unchanged or within safe limits.81
Baek et al (2016) investigated fig paste (standardized to contain 1.7% fiber; Yeongam Green Fig Agriculture Co. Ltd.; Yeongam, South Korea) for the management of functional constipation in a randomized, double-blind, placebo-controlled trial. Patients with functional constipation were treated with fig paste (n = 40) or placebo (n = 40) for eight weeks. The primary outcome was colon transit time. Fig paste was found to significantly reduce colon transit time and improve stool type and abdominal discomfort compared to placebo.82 Clinical parameters showed no signs of adverse effects.
Pourmasoumi et al (2019) established that consumption of flixweed (Descurainia sophia, Brassicaceae) seed or fig fruit caused a significant improvement in irritable bowel syndrome (IBS) symptoms in a randomized controlled trial with 150 patients with IBS. Patients received either flixweed (60 g/d; n = 48), fig (90 g/d; n = 46), or no supplementation (n = 48) for four months. IBS symptoms were assessed at baseline and monthly. Secondary outcomes were anthropometric measures taken at baseline and at the end of the intervention. One hundred and forty-two participants completed the trial. Both flixweed and fig supplementation resulted in a significant improvement in defecation and hard stool frequency, abdominal distention, pain frequency, and quality of life. C-reactive protein, an inflammation marker and one of the anthropometric measures, however, remained unchanged. The authors speculate that inadequate fiber intake, a shortcoming of this study, may have affected the findings.83
Bahadori et al (2016) conducted a clinical investigation on the effects of an olive oil/olive fruit/fig fruit preparation (2:5:1 w/w formulated as a semisolid mixture) on rheumatoid arthritis remission indicators. Fifty-six patients received either methotrexate (MTX) only (n = 27) or MTX plus fig/olive supplement (n = 29) for 16 weeks. Only non-significant differences between remission indicators in the two study groups were observed. However, a trend in favor of supplementation was indicated by Patient Global Assessment score improvements in the fig/olive group.84 In a separate study, the same group reported on the safety of fig/olive supplementation concomitantly with MTX in patients with rheumatoid arthritis. Differences between lipid profile indicators and fasting blood sugar in the two groups were not statistically significant. Supplementation was found to be safe and did not significantly affect any of the measured clinical parameters.85
As is typical for common fruits and foods, consumption is assumed to be safe based on centuries-long traditional uses. Fig falls into this category and consequently no studies of safety or toxicity were found. However, allergic reactions due to fig consumption, including anaphylaxis and contact urticaria, have been reported.86-89
Adulteration or substitution of fig fruit with other plant materials or species is not known to occur. With regard to potential contamination, the FDA has established a defect action level — the limit at which the FDA will regard a food product as “adulterated” (and therefore subject to enforcement action) — for figs of “average of 10% or more by count are insect-infested and/or moldy and/or dirty fruit or pieces of fruit.”90
SUSTAINABILITY AND FUTURE OUTLOOK
The International Union for Conservation of Nature (IUCN) assigns wild F. carica to the conservation category of least concern (LC), meaning that the species is not considered to be threatened.4 However, its status may vary by region. For example, the species has been classified as endangered in Kurram Valley in Parachinar, Pakistan,91 and, while once widespread in the Nakhchivan Autonomous Republic within Azerbaijan, F. carica is now reportedly in danger of disappearance.92 Accessions are being maintained at the Genetic Resources Institute and the Research Institute of Horticulture and Subtropical Crops, both in Azerbaijan. Sustainability of cultivated fig tree crops is dependent on biodiversity conservation, genetic diversity, and long-term survival of wild populations of not only F. carica, but all Ficus species.
Genetic variability studies also have been carried out regionally, for example using simple sequence repeat (SSR) and amplified fragment length polymorphism (AFLP) markers. Genetic diversity analyses and cultivar fingerprinting can provide insight about conservation and species management.93 A genetic and phenotypic diversity study in Estahban, Fars province, Iran, showed high diversity between male wild fig accessions. The researchers suggested that the observed diversity could be due to the antiquity of fig in Estahban and that the data on “current levels of genetic diversity of germplasm [are] essential for devising strategies for male fig conservation.”8 Another Iranian study investigated infraspecific (a taxonomic level below species, such as subspecies, varieties, or cultivars) genetic variations and population structure of fourteen F. carica tree populations using the random amplified polymorphic DNA (RAPD) molecular technique. The purpose was to identify different genotypes in Iran to implement conservation and breeding programs.94
Certified organic figs and fig preparations are now produced on a large scale and exported into the global market by several Asian countries (especially Turkey, but also Iran, Israel, and Pakistan) and northern African countries (Egypt, Morocco, and Tunisia). Organic figs also are produced on a large scale in the United States, especially in California, but also to some extent in Oregon, Washington, Hawaii, Florida, South Carolina, and Texas, among other states, and in neighboring Mexico (Baja California, Jalisco, and Tlaxcala).95 The sustainability of the fig raw material supply, whether from wild collection or cultivation, appears stable at this time, considering its conservation status of least concern, thousands of years of cultivation in several countries, ongoing research to identify and conserve wild genetic resources, and a significant increase in commercial production according to sustainable agriculture standards. However, studies that assess changes in area of suitable fig habitat in view of climate change adaptation are warranted.
- Lansky EP, Paavilainen HM, eds. Figs: The Genus Ficus. Boca Raton, FL: CRC Press; 2011.
- Rønsted N, Weiblen GD, Clement WL, Zerega NJC, Savolainen V. Reconstructing the phylogeny of figs (Ficus, Moraceae) to reveal the history of the fig pollination mutualism. Symbiosis. 2008;45(1-3):45-55.
- Aradhya MK, Stover E, Velasco D, Koehmstedt A. Genetic structure and differentiation in cultivated fig (Ficus carica L.). Genetica. 2010;138(6):681-694.
- Participants of the FFI/IUCN SSC Central Asian regional tree Red Listing workshop. Ficus carica. The IUCN Red List of Threatened Species 2007: e.T63527A12687229. Bishkek, Kyrgyzstan. 2007.
- Taeb M. Islamic Republic of Iran: Country Report to the FAO International Technical Conference on Plant Genetic Resource. Leipzig, Germany: Food and Agriculture Organization of the United Nations; 1996.
- Muminjanov H, Karagöz A, eds. Biodiversity of Turkey. Contribution of Genetic Resources to Sustainable Agriculture and Food Systems. Ankara, Turkey: Food and Agriculture Organization of the United Nations; 2018.
- Giraldo E, Lopez-Corrales M. Optimization of the management of an ex-situ germplasm bank in common fig with SSRs. J Amer Soc Hort Sci. 2008;133(1):69-67.
- Khadivi-Khub A, Anjam K. Characterization and evaluation of male fig (caprifig) accessions in Iran. Plant Syst Evol. 2014;300(10):2177-2189.
- Caliskan O, Bayazit S, Ilgin M, Karatas N. Morphological diversity of caprifig (Ficus carica var. caprificus) accessions in the eastern Mediterranean region of Turkey: Potential utility for caprification. Sci Hortic. 2017;222:46-56.
- Zarei M, Azizi M, Rahemi M, Tehranifar A. Evaluation of NaCl salinity tolerance of four fig genotypes based on vegetative growth and ion content in leaves, shoots, and roots. HortScience. 2016;51(11):1427-1434.
- Caliskan O, Bayazit S, Ilgin M, Karatas N, Ergul A. Genetic diversity and population structure in caprifigs (Ficus carica var. caprificus) using SSR markers. Span J Ag Res. 2018;16(3):e0703.
- Commission Suisse de Pharmacopée. Pharmacopoea Helvetica, 11. Ausgabe, Supplement 11.3. Deutsche Ausgabe. Bern, Switzerland: Swissmedic, Schweizerisches Heilmittelinstitut; 2019.
- Machado CA, Robbins N, Gilbert MTP, Herre EA. Critical review of host specificity and its coevolutionary implications in the fig/fig-wasp mutualism. Proc Natl Acad Sci. 2005;102(suppl 1):6558-6565.
- Kjellberg F, Lesne A. Ficus carica and its pollination. Villeurbanne, France: HAL archives ouvertes; 2020.
- Yeşil Y, Çelik M, Yılmaz B. Wild edible plants in Yeşilli (Mardin-Turkey), a multicultural area. J Ethnobiology Ethnomedicine. 2019;15(1):52.
- UN Comtrade Database. 2020. https://comtrade.un.org/. Accessed May 25, 2020.
- Global Agricultural Trade System (GATS) Online. USDA Foreign Agricultural Service; 2020. Available at: https://apps.fas.usda.gov/gats/. Accessed May 25, 2020.
- Shi Y, Mon AM, Fu Y, et al. The genus Ficus (Moraceae) used in diet: Its plant diversity, distribution, traditional uses and ethnopharmacological importance. J Ethnopharmacol. 2018;226:185-196.
- Unani Pharmacopoeia Committee. The Unani Pharmacopoeia of India. Vol II. New Delhi, India: Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH), Ministry of Health & Family Welfare, Government of India; 2007.
- Cumo C, ed. Encyclopedia of Cultivated Plants: From Acacia to Zinnia. Volume 1: A–F. Santa Barbara, CA: ABC-CLIO, LLC; 2013.
- Linné Cv. Caroli Linnæi ... Genera plantarum eorumque characteres naturales secundum numerum, figuram, situm, & proportionem omnium fructificationis partium. Lugduni Batavorum: apud C. Wishoff; 1737.
- Linné CV, Salvius L. Caroli Linnaei ... Systema naturae per regna tria naturae :secundum classes, ordines, genera, species, cum characteribus, differentiis, synonymis, locis. Holmiae (Stockholm): Impensis Direct. Laurentii Salvii; 1759.
- Marzell H. Wörterbuch der deutschen Pflanzennamen. 2. Band. Stuttgart/Wiesbaden: S. Hirzel Verlag/Franz Steiner Verlag; 1977.
- Condit I. Fig varieties: a monograph. Hilgardia. 1955;23(11):323-538.
- Fuller DQ, Stevens CJ. Between domestication and civilization: the role of agriculture and arboriculture in the emergence of the first urban societies. Veget Hist Archaeobot. 2019;28(3):263-282.
- Kislev ME, Hartmann A, Bar-Yosef O. Early domesticated fig in the Jordan Valley. Science. 2006;312(5778):1372-1374.
- Lev-Yadun S, Ne’eman G, Abbo S, Flaishman MA. Comment on “Early domesticated fig in the Jordan Valley.” Science. 2006;314(5806):1683-1683.
- Akkermans PMMG. Living on the edge or forced into the margins? Hunter-herders in Jordan’s northeastern badlands in the Hellenistic and Roman Periods. J East Mediterr Archaeol Heritage Stud. 2019;7(4):412-431.
- Day J. Botany meets archaeology: People and plants in the past. J Exp Bot. 2013;64(18):5805-5816.
- Fatkin DS, Adelsberger K, Farahani A, et al. Digging deeper: Technical reports from the Dhiban Excavation and Development Project (2004-2009). Annual of the Department of Antiquities of Jordan. 2011;55:249-266.
- Frumin SI, Tchekhanovets Y. Plant imprints on pottery reveal fig tree in Hellenistic Jerusalem. Israel Exploration Journal. 2016;66(2):188-201.
- Meyer FG. Carbonized food plants of Pompeii, Herculaneum, and the Villa at Torre Annunziata. Econ Bot. 1980;34(4):401-437.
- Lardos A, Heinrich M. Continuity and change in medicinal plant use: The example of monasteries on Cyprus and historical iatrosophia texts. J Ethnopharmacol. 2013;150(1):202-214.
- Nedelcheva AM. Plants related to the life and medicinal practice of St. Ivan Rilski. In: Morel J-P, Mercuri AM, eds. Plants and Culture: Seeds of the Cultural Heritage of Europe. Bari, Itlay: Edipuglia; 2009:175-178.
- Nedelcheva A. Medicinal plants from an old Bulgarian medical book. J Med Plants Res. 2012;6(12):2324-2339.
- Dennell RW. Seeds from a Medieval sewer in Woolster Street, Plymouth. Econ Bot. 1970;24(2):151-154.
- Jarić S, Mitrović M, Djurdjević L, et al. Phytotherapy in medieval Serbian medicine according to the pharmacological manuscripts of the Chilandar Medical Codex (15–16th centuries). J Ethnopharmacol. 2011;137(1):601-619.
- Dolatkhahi M, Dolatkhahi A, Nejad JB. Ethnobotanical study of medicinal plants used in Arjan - Parishan protected area in Fars Province of Iran. Avicenna J Phytomed. 2014;4(6):402-412.
- Ghazanfar SA, Al-Al-Sabahi AM. Medicinal plants of Northern and Central Oman (Arabia). Econ Bot. 1993;47(1):89-98.
- Brussell DE. Medicinal plants of Mt. Pelion, Greece. Econ Bot. 2005;58(Supplement):SI74-S202.
- De Natale A, Pollio A. Plants species in the folk medicine of Montecorvino Rovella (inland Campania, Italy). J Ethnopharmacol. 2007;109(2):295-303.
- Łuczaj Ł, Jug-Dujaković M, Dolina K, Vitasović-Kosić I. Plants in alcoholic beverages on the Croatian islands, with special reference to rakija travarica. J Ethnobiol Ethnomed. 2019;15(1):51.
- United States Pharmacopoeial Convention. The Pharmacopoeia of the United States of America 1820. Boston, MA: Charles Ewer; 1820.
- Wood GB, Bache F. The Dispensatory of the United States of America. Philadelphia, PA: Grigg & Elliot; 1833.
- United States Pharmacopoeial Convention. The Pharmacopoeia of the United States of America Ninth Decennial Revision. Philadelphia: P. Blakiston’s Son & Company; 1910.
- Committee on National Formulary. The National Formulary Fourth Edition. Washington, D.C.: American Pharmaceutical Association; 1916.
- Brinckmann J, Marles R, Schiff P, et al. Quality standards for botanicals. Legacy of USP’s 200 years of contributions. HerbalGram. 2020;126:50-65.
- US Federal Trade Commission. TITLE 16 — COMMERCIAL PRACTICES. Chapter I — Federal Trade Commission [Docket No. 5069J. Part 3 — Digest of Cease and Desist Orders. UNIVERSAL LABORATORIES, ETC. Federal Register. 1948;13(158):4690-4693.
- Deutsche Arzneibuch-Kommission. Ergänzungsbuch zum Deutschen Arzneibuch (Arzneimittel, die im Deutschen Arzneibuch, 6. Allsgabe, nicht -enthalten sind). Sechste Ausgabe (Erg.-B.6). Neudruck 1948. Berlin und Frankfurt, Deutschland: Deutscher Apotheker-Verlag GmbH; 1948.
- Zepernick B. Die Arzneipflanzen in den deutschsprachigen Pharmakopöen der Gegenwart. Willdenowia. 1975;7(3):591-653.
- Blumenthal M, Busse WR, Goldberg A, et al., eds. The Complete German Commission E Monographs - Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston, MA: Integrative Medicine Communication; 1998.
- United States Department of Agriculture. United States Standards for Grades of Dried Figs - Effective December 21, 2001. Washington, DC: United States Department of Agriculture, Agricultural Marketing Service; 2001.
- US Food and Drug Administration. Title 21 - Food and Drugs. Chapter I. Part 145 - CANNED FRUITS. Subpart B - Requirements for Specific Standardized Canned Fruits. In: Code of Federal Regulations. Washington, DC: National Archives and Records Administration; 2019.
- Office of Dietary Supplements and the National Library of Medicine. Dietary Supplement Label Database. Bethesda, MD: National Institutes of Health; 2020.
- Natural and Non-prescription Health Products Directorate. Natural Health Products Ingredients Database. Ottawa, Ontario: Health Canada; 2020.
- Natural and Non-prescription Health Products Directorate. Natural Health Product: Antioxidants. Ottawa, Ontario: Health Canada; 2017.
- European Commission. Cosmetic ingredient (CosIng) database. Brussels, Beglium: DG Internal Market, Industry, Entrepreneurship and SMEs; 2020.
- European Commission. Notification Detail: Decree regulating the use of vegetable substances and preparations in food supplements, replacing the Decree of the Minister for Health of 9 July 2012. Brussels, Belgium: Directorate-General for Internal Market, Industry, Entrepreneurship and SMEs; 2017.
- European Food Safety Authority. Consolidated list of Article 13 health claims. List of references received by EFSA. Part 4. IDs 3001 – 4705. Parma, Itlay: European Food Safety Authority;2011.
- EFSA Panel on Dietetic Products Nutrition and Allergies (NDA). Scientific Opinion on the substantiation of health claims related to various food(s)/food constituent(s) and protection of cells from premature aging, antioxidant activity, antioxidant content and antioxidant properties, and protection of DNA, proteins and lipids from oxidative damage pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal. 2010;8(2):1489. [1463 pp.].
- Bundesamt für Verbraucherschutz und Lebensmittelsicherheit. List of Substances of the Competent Federal Government and Federal State Authorities. Category “Plants and plant parts”. Cham, Switzerland; Heidelberg, Germany; New York, New York; Dordrecht, Netherlands; London, United Kingdom: Springer; 2014.
- Badgujar SB, Patel VV, Bandivdekar AH, Mahajan RT. Traditional uses, phytochemistry and pharmacology of Ficus carica: A review. Pharm Biol. 2014;52(11):1487-1503.
- Al-Snafi AE. Nutritional and pharmacological importance of Ficus carica - A review. IOSR J Pharm. 2017;7(3):33-48.
- Jagtap UB, Bapat VA. Exploring Phytochemicals of Ficus carica L. (Fig). In: Murthy HN, Bapat VA, eds. Bioactive Compounds in Underutilized Fruits and Nuts. Cham, Switzerland: Springer International Publishing; 2020:353-368.
- Alamgeer, Iman S, Asif H, Saleem M. Evaluation of antihypertensive potential of Ficus carica fruit. Pharm Biol. 2017;55(1):1047-1053.
- Debib A, Dueñas M, Boumediene M, Mothana RA, Latifa A, Tir-Touil MA. Synergetic hepatoprotective effect of phenolic fractions obtained from Ficus carica dried fruit and extra virgin olive oil on CCL4-induced oxidative stress and hepatotoxicity in rats. J Food Biochem. 2016;40(4):507-516.
- Alsahli MA, Almatroudi A, Khan AA, Alhumaydhi FA, Alrumaihi F, Rahmani AH. Ficus carica (Fig) fruit extract attenuates CCl4-induced hepatic injury in mice: A histological and immuno-histochemical study. Int J Pharmacol. 2019;15(3):370-376.
- Kore KJ, Shete RV, Kale BN, Borade AS. Protective role of hydroalcoholic extract of Ficus carica in gentamicin induced nephrotoxicity in rats. Int J Pharm Life Sci. 2011;2(8):978-982.
- Gilani AH, Mehmood MH, Janbaz KH, Khan A-u, Saeed SA. Ethnopharma cological studies on antispasmodic and antiplatelet activities of Ficus carica. J Ethnopharmacol. 2008;119(1):1-5.
- Oh H-G, Lee H-Y, Seo M-Y, et al. Effects of Ficus carica paste on constipation induced by a high-protein feed and movement restriction in beagles. Lab Anim Res. 2011;27(4):275-281.
- Lee H-Y, Kim J-H, Jeung H-W, et al. Effects of Ficus carica paste on loperamide-induced constipation in rats. Food Chem Toxicol. 2012;50(3):895-902.
- Rtibi K, Grami D, Wannes D, et al. Ficus carica aqueous extract alleviates delayed gastric emptying and recovers ulcerative colitis-enhanced acute functional gastrointestinal disorders in rats. J Ethnopharmacol. 2018;224:242-249.
- Deepa P, Sowndhararajan K, Kim S, Park SJ. A role of Ficus species in the management of diabetes mellitus: A review. J Ethnopharmacol. 2018;215:210-232.
- El-Shobaki FA, El-Bahay AM, Esmail RS, El-Megeid AA, Esmail NS. Effect of figs fruit (Ficus carica L.) and its leaves on hyperglycemia in alloxan diabetic rats. World J Dairy Food Sci. 2010;5(1):47-57.
- Belguith-Hadriche O, Ammar S, Contreras MdM, et al. Antihyperlipidemic and antioxidant activities of edible Tunisian Ficus carica L. fruits in high fat diet-induced hyperlipidemic rats. Plant Foods Hum Nutr. 2016;71(2):183-189.
- Gul S, Raza S, Rashid Z, Ayub M, Sarwar G. Neuropharmacological screening of Ficus carica Linn fruit for anxiolytic and antidepressant activity. Bangladesh J Med Sci. 2018;17(4):606-611.
- Alharthy NA, Bawazir AE. Effects of the mixture dried figs (Ficus carica) and olive oil on amnesia model of Alzheimer’s induced by scopolamine in male albino rats. Pharmacophore. 2019;10(4):62-71.
- Leber A, Hontecillas R, Tubau-Juni N, Zoccoli-Rodriguez V, Goodpaster B, Bassaganya-Riera J. Abscisic acid enriched fig extract promotes insulin sensitivity by decreasing systemic inflammation and activating LANCL2 in skeletal muscle. Sci Rep. 2020;10(1):10463.
- Atkinson FS, Villar A, Mulà A, et al. Abscisic acid standardized fig (Ficus carica) extracts ameliorate postprandial glycemic and insulinemic responses in healthy adults. Nutrients. 2019;11:1757.
- Sardari M, Rezaeizadeh H, Minaei B, Heydari M. Ficus carica (fig) paste supplementation in patients with multiple sclerosis associated constipation; a double blind randomized clinical trial. Planta Med. 2015;81(16):SL2A_04.
- Tofighi Z, Golabi M, Toliyat T, Naseri M, Yassa N. Formulation and evaluation of an Iranian traditional dosage form containing Linum and Ficus for improvement of functional constipation. Jundishapur J Nat Pharm Prod. 2017;12(4):e40069.
- Baek HI, Ha KC, Kim HM, et al. Randomized, double-blind, placebo-controlled trial of Ficus carica paste for the management of functional constipation. Asia Pac J Clin Nutr. 2016;25(3):487-496.
- Pourmasoumi M, Ghiasvand R, Darvishi L, Hadi A, Bahreini N, Keshavarzpour Z. Comparison and assessment of flixweed and fig effects on irritable bowel syndrome with predominant constipation: A single-blind randomized clinical trial. EXPLORE. 2019;15(3):198-205.
- Bahadori S, Ahmadzadeh A, Shams Ardekani MR, Kamalinejad M, Keshavarz M, Salamzadeh J. Does regular use of a complementary medicine of Olea europa and Ficus carica have adverse effects on lipid profile and fasting blood glucose of rheumatoid arthritis (RA) patients under treatment with DMARD regimens containing methotrexate? Iranian J Pharm Res. 2016;15(4):933-940.
- Bahadori S, Salamzadeh J, Kamalinejad M, Shams Ardekani MR, Keshavarz M, Ahmadzadeh A. Study of the effect of an oral formulation of fig and olive on rheumatoid arthritis (RA) remission indicators: A randomized clinical trial. Iranian J Pharm Res. 2016;15(3):537-545.
- Dechamp C, Bessot J-C, Pauli G, Deviller P. First report of anaphylactic reaction after fig (Ficus carica) ingestion. Allergy. 1995;50(6):514-516.
- Gandolfo M, Baeza M, De Barrio M. Anaphylaxis after eating figs. Allergy. 2001;56(5):462-463.
- Cruz NV, Bahna SL, Knight AK. Fig allergy: Not just oral allergy syndrome (OAS). J Allergy Clin Immunol. 2007;119(1, Supplement):S110.
- Urbani S, Aruanno A, Nucera E. Adverse reaction to Ficus carica: reported case of a possible cross-reactivity with Der p1. Clin Mol Allergy. 2020;18(1):9.
- US Food and Drug Administration. Food Defect Levels Handbook. Silver Spring, MD: US Food and Drug Administration; 2005.
- Hussain W, Hussain J, Ali R, Khan I, Khan Shinwari Z, Andrade Nascimento I. Tradable and conservation status of medicinal plants of Kurram Valley, Parachinar, Pakistan. J App Pharm Sci. 2012;2(10):066-070.
- Government of Azerbaijan. National Report on the State of Plant Genetic resources for Food and Agriculture in Azerbaijan. Baku, Azerbaijan: Food and Agriculture Organization of the United Nations (FAO) Partnership and Liaison Office in the Republic of Azerbaijan; 2006.
- Baraket G, Chatti K, Saddoud O, et al. Comparative assessment of SSR and AFLP markers for evaluation of genetic diversity and conservation of fig, Ficus carica L., genetic resources in Tunisia. Plant Mol Biol Rep. 2011;29(1):171-184.
- Zolfaghari MR, Salimpour F, Sharifnia F, Peyvandi M, Marandi SJ. Analysis of genetic diversity among Iranian populations of Ficus carica L. (Moraceae). Acta Biol Sib. 2019;5(3):131-138.
- United States Department of Agriculture. Organic INTEGRITY Database. Washington, DC: USDA Agricultural Marketing Service; 2020.