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Ingredient review

Ginger (Zingiber officinale)

Description

What is it?

Zingiber officinale, or ginger, is a well-known herb that is used globally for it’s flavor and remedial health effects. It has been used traditionally for thousands of years in India and China and for more than 1,000 years in Europe. (136)

Containing more than 400 biological constituents, ginger has a broad spectrum of pharmacological effects including as an anti-emetic, anti-inflammatory, anti-microbial, anti-lipidemic, anti-hyperglycemic, anti-tumorigenic, anti-oxidant, and immunomodulator.  (4)(8)(120)(136)

The primary constituents contributing to ginger’s wide array of biological activities, as well as its pungent aroma and flavor, are 6-gingerol and 6-shogaol. (84)(145) Gingerols are isolated from the plant’s rhizomes, whereas shogaols are produced when the rhizomes are heated or dehydrated. (145)

An exponential increase in the number of published trials was seen from 2000 to 2010, including a large number of systematic reviews and meta-analyses from 2008 onwards, indicating an increasing interest in ginger’s therapeutic benefits. (8)(91)

Main uses

Analgesic
Antiemetic for chemotherapy, pregnancy, or surgery
Anti-inflammatory and antioxidant
Cardiometabolic and anti-diabetic
Gastric motility
Menstrual regulation

Formulations

Formulation
Comparison
Foods/tea
Measures generally equivalent to 1,000 mg of dried ginger powder: One teaspoon of fresh grated raw rhizome; Two one-inch by ¼-inch pieces of crystalized ginger; Four cups (eight oz/cup) of commercial ginger tea or 1/2 teaspoon of grated ginger steeped for 5-10 minutes (26)
Ginger powders, capsules, or tablets
May contain raw rhizome powder or standardized extracts; Many standardized extracts range between 1-5% gingerol/shogaols, though some containing 20-25% may be found. Examples of standardized extract formulations found in research include:
Eurovita extract 33 (EV.EXT 33): An ethanolic standardized extract containing 1.9% by weight of 6-, 8-, and 10-gingerol (166)
Eurovita extract 35 (EV.EXT 35): A 12-20:1 standardized extract equivalent to 1,500-2,000 mg of dry ginger (37)(168)
Eurovita extract 77 (EV.EXT 77): A mixture of extracts from ginger and Alpina galanga (blue ginger) standardized to contain >30 mg hydroxymethoxyphenyl compounds and acetoxychavicol acetate in 255 mg of mixed extract (52)
Zintoma®: Dry root powder formulated as a 10:1 ethanolic (50%) extract standardized to contain 5.38 mg (2.15%) 6-gingerol, 1.8 mg (0.72%) 8-gingerol, 4.19 mg (1.78%) 10-gingerol, and 0.92 mg (0.37%) 6-shogaol (139)
Zintona EC: Enteric-coated standardized extract containing 10 mg of 6-gingerol per 250 mg capsule (167)
Liquid extracts
Measures generally equivalent to 1,000 mg of dried ginger powder: Two droppers (two mL) of liquid extract (26)

Dosing & administration

Adverse effects

Ginger is generally recognized as safe (GRAS) by the United States Food and Drug Administration (FDA). (84) Doses up to 6,000 mg may be applied with a low risk of mild adverse effects. (18) Heartburn appears to be documented regularly across trials, with the frequency of reports ranging between 3% to 27%. (169) Low incidences of gastrointestinal distress, nausea, and diarrhea may be reported but the prevalence is generally no greater than in controls. (8)(33)(101)(120)(163)(169)

Some studies show a higher frequency of minor gastrointestinal adverse events compared to a placebo. (6)(17) Other reports include low rates of headache (2%), cardiovascular symptoms (3.5%), respiratory symptoms (3.4%), flu-like symptoms (1.7%), intense feelings of needing to urinate (25%), and bruising, flushing or rash, but rates are generally no higher than those observed in control groups. (8)(101)

Meta-analyses and systematic reviews show no greater risk of adverse effects from ginger during pregnancy to the mother or the future offspring. (155)(163) While ginger has been described to inhibit platelet aggregation in vitro, theoretically increasing the risk of bleeding, evidence for this effect in humans remains equivocal, even with concomitant blood-thinning medications such as warfarin. (65)(67)(103)

Pharmacokinetics

Absorption

  • Gingerols may be extensively glucuronidated in the stomach, intestine, and liver prior to absorption into the bloodstream, contributing to low bioavailability.
  • (115)
  • (165)
  • Free 6-, 8-, and 10-gingerol and 6-shogaol are not detectable in plasma post-oral ingestion between doses of 100 to 2,000 mg of a standardized extract (5% gingerols) in healthy Px. (176)
  • Glucuronide and sulfate conjugates are rapidly found in the blood, appearing within 30 minutes post-oral ingestion, with max concentrations achieved between 45 to 120 minutes using a standardized extract (5% gingerols) in healthy Px. (176)
  • 6-Gingerol and 6-shogaol were detectable with 2,000 mg of a suspension of red ginger (Z. officinale var. Rubrum), with max concentrations reached within ~30 to 40 minutes in healthy Px. (90)

Distribution

  • Conjugated gingerol and shogaol are proposed to enter tissues where they are deconjugated back into their free forms to exert their pharmacological effects. (115)
  • Gingerol and shogaol are widely distributed across tissues but particularly in the stomach, intestine, liver, lung, and kidney, as shown in rats. (92)(115)
  • Various constituents may pass the blood-brain barrier via passive diffusion, including 6- and 8-gingerol, 6-shogaol, and zingerone. (92)(115)(150)

Metabolism

  • Gingerols and shogaols may be primarily eliminated via phase II glucuronide conjugation, as shown in rats. (114)
  • Free gingerol and shogaols are mainly metabolized to glucuronide conjugates at doses up to 2,000 mg of a standardized extract (5% gingerols), though one third of 6-gingerol may be sulfate conjugates at this dose in humans. (176)
  • In vitro studies show an inconsistent inhibitory effect on numerous metabolic cytochromes, possibly reflecting variance in the concentration of specific constituents found in ginger products. (86)
  • Many individual constituents may or may not individually inhibit numerous cytochromes, (79)(86)(93)(174) but ginger extracts containing a natural mixture of constituents have shown in vitro inhibitory activity of CYP3A4, CYP2C9, and CYP2C19. (80)(81)
  • However, in vitro concentrations required to inhibit these enzymes by 50% are typically 2-4 times higher than observed ginger phenolic plasma concentrations, indicating low likelihood of clinically relevant interactions. (113

Excretion

  • Half-life of 6-, 8-, and 10-gingerol and 6-shogaol glucuronide and sulfate conjugates ranged between 1.25-2.0 hours at the 2,000 mg dose of a standardized extract (5% gingerols) in healthy Px. (176)
  • Half-life of 6-gingerol and 6-shogaol were 5.5 and 2.5 hours, respectively, with 2,000 mg of a suspension of red ginger (Z. officinale var. Rubrum) in healthy Px. (90)
  • Conjugates are typically non-detectable in plasma after four hours in humans. (176)
  • 6-Gingerol and 6-shogaol are primarily excreted in the bile, but can also be detected in urine, as shown in rats. (15)(117)

References