Daily Ginger Drinking and Platelet Function
Condition: Platelets Dysfunction; Hematological Diseases
MeSH terms: Hematologic Diseases
Study type: Interventional

Summary: 
      This study aims to examine the effect of ginger beverage consumption on platelets activity in
      apparently healthy Saudi adult volunteers.

      As for the Saudi population, consumption of powdered ginger dissolved in hot water is a
      common practice. Accordingly, in this study, it is tempting to speculate the effect of this
      form of ginger consumption, given in separate time points per day, on platelet aggregation
      profile by using platelet aggregation analogues. If positive results were obtained, the herb
      could provide natural protection against the development of platelet aggregation
      complications and could be a potential alternative to aspirin, used for improving blood
      circulation and hematological pathophysiologies in diseased individuals.
    

Detailed description: 
      Herbal medicine products are dietary supplements that people take to improve their health.
      Many herbs have been used for a long time for claimed health benefits. They are sold as
      tablets, capsules, powders, beverages, extracts and fresh or dried plants. Herbal medicines
      have been associated with treatment of several physiological disorders of which
      hematological, mainly clotting disorders. Those include garlic, onion, and ginger in addition
      to pharmacological reagents such as aspirin, warfarin, heparin, and others. One of the herbal
      medications affecting hematological profile is ginger which has gained focus throughout
      studies conducted in previous years in the field of inhibiting platelet aggregation, taking
      benefit from some undesirable side effects arising from the use of other anti-platelet
      aggregation agents, especially aspirin.

      Ginger (Zingiber officinale) is a well known spice and flavoring agent used in traditional
      medicine in many countries. It is a source of valuable phytonutrients characterized by having
      aromatic odor and pungent taste. The ginger rhizome contains 60% starch, 10%proteins, 10%
      fats, 5% fibers, 6% inorganic material, 10% residual moisture, 1-4% essential oils including
      gingerol and zingiberene, in addition to pungent principles such as zingerone, gingerol and
      shogaol. Shogaols are produced by heating gingerols. It has been speculated that ginger can
      eliminate symptoms associated with a variety of illnesses since there are a variety of
      chemical classes that these compounds belong to. Ginger has been used in the management of
      headache, nervous diseases, nausea, and vomiting. It has also been used to treat migraine
      headaches without side-effects. In addition, it is recommended in the management of rheumatic
      disorders and muscular pain. Ginger also acts as a metabolic enhancer where acetone extracts
      of ginger have stimulated bile secretion and excretion of gallstones. Although ginger is
      considered a safe herbal medicine with only few and insignificant adverse side effects, few
      undesirable effects like heartburn were noticed. In quantities higher than 6 g ginger may act
      as a gastric irritant and inhalation of dust from ginger may produce immunoglobulin E
      (IGE)-mediated allergy.

      As for ginger toxicity, an acute overdose of ginger is usually in excess of about 2g of
      ginger per kilogram of body mass depending on the ginger tolerance level and can result in a
      state of central nervous system over-stimulation called "ginger gitters".

      Experimental data reveals that ginger may be a dual inhibitor of eicosanoid synthesis,
      inhibiting the synthesis of both prostaglandins and leukotrienes, which are inflammatory
      mediators produced from arachidonic acid. With reference to the fact that normal platelet
      functioning is linked to an interplay between those substances, ginger consumption appears to
      be linked with reducing platelet aggregation.

      Platelets have traditionally been linked with concepts of hemostasis and hemorrhagic
      disorders. However, with increasing incidence of atherosclerosis and hematologic disorders,
      the critical role played by platelets is more evident. Platelets are no longer viewed as
      "scaffolding" for the events of the coagulation cascade but rather as important catalysts in
      hemostasis, thrombosis, and fibrinolysis. Improved understanding of platelet physiology has
      led to developments of pharmacologic adjuncts resulting in improved patency rates and
      improved patient outcomes. Platelets are the smallest components in the blood stream, where
      they exist as a-nucleate disc-shaped cells in their resting state and travel singly as
      discoidal particles. In the presence of stimuli such as arachidonic acid, activated platelets
      change shape into spiny spheres. They bind to fibrinogen, aggregate and release the contents
      of their intracellular granules, including adenosine diphosphate (ADP) and serotonin.

      ADP and an arachidonic acid (AA) metabolite acting an endogenous platelet activator,
      thromboxane A2 (TxA2), intensify the extent of platelet aggregation. ADP, arachidonic acid,
      epinephrine, and collagen act as agonists for platelet aggregation and clumping. These
      substances act in positive feedback loops, making platelet aggregation an autocatalytic
      rather than equilibrium response. Under pathophysiological conditions, platelet activation
      may result in peripheral, cardiovascular or cerebrovascular thrombosis with serious
      consequences.

      Aspirin has been the main anti-platelet therapeutic agent. Inhibition of platelet aggregation
      by aspirin significantly reduces the incidence of first myocardial infarction, recurrent
      infarction and vascular death among patients with cardiovascular disease. Aspirin also
      reduces the risk of nonfatal stroke, nonfatal myocardial infarction and vascular death in
      patients with possible risk factors. However, aspirin ingestion, is mainly associated with
      gastric ulcers and gastrointestinal bleeding. Thus, the use of aspirin may be confined to
      elderly patients whose benefits outweigh increased risks of gastrointestinal bleeding.

      Gingerols and their derivatives, especially [8]-paradol, have been reported to be more potent
      anti-platelet and cyclo-oxygenase-1 (COX-1) inhibitors than aspirin, when tested in vitro by
      the Chrono Log whole blood platelet aggregometer. Note that COX-1 is the enzyme responsible
      for the conversion of arachidonic acid into important biological mediators including
      prostaglandins, prostacyclins, and thromboxanes. These authors proposed that the carbonyl
      functional group at C3 found in paradol and in the diarylheptanoid series may contribute to
      their potent anti-platelet activity and inhibition of COX-1. Inhibition of the arachidonic
      acid (AA) metabolism cascade via the COX-1/thromboxane synthase system by these phenolic
      compounds may underline the mechanism of their action. In 2001 Koo et al. compared the
      ability of gingerols and related analogs to that of aspirin in inhibiting AA-induced human
      platelet serotonin release in vitro. Using the same dose range, it has been found that
      gingerols and related analogs were approximately two- to three-fold less potent than aspirin
      against the platelet release reaction initiated by AA, and two- to four-fold less potent than
      aspirin at inhibiting AA-induced platelet aggregation. Gingerols inhibited COX activity,
      assessed by measuring prostaglandin D2, a product of AA metabolism by COX. These results
      suggest that inhibition of COX activity by gingerols and related analogs may be the
      underlying mechanism for their effect on AA-induced platelet activation. 6-gingerol inhibits
      arachidonic acid-induced platelet aggregation and formation of thromboxane B2 and
      prostaglandin D2. Gingerol, shogaol and other structurally related substances in ginger
      inhibit prostaglandin and leukotriene biosynthesis.

      Of the earlier studies conducted on ginger was that of Srivastava et al. in 1986 where they
      found that 5g of fresh, raw ginger has inhibited thromboxane B2 formation.

      Furthermore, a study done on 20 healthy male individuals that were given 50 g of butter and
      5g of ginger a day for seven days showed that addition of ginger with a fatty meal inhibited
      the platelet aggregation induced by adenosine diphosphate and epinephrine greatly. Ginger has
      been reported to inhibit prostaglandin synthesis in vitro. Dietary fat content affects
      platelet aggregation by modifying prostaglandin metabolism. Administration of ginger in a
      fatty diet inhibits the transformation of arachidonic acid to thromboxane and decreases the
      sensitivity of platelets to many aggregating agents. In 1994, Lumb et al., have shown in a
      cross over study conducted on 8 subjects that 2g of powdered ginger (prepared as medication)
      had no effect on bleeding time and whole blood platelet aggregation. Similarly, 15g and 40g
      of fresh or cooked raw ginger did not induce platelet aggregation in a cross over study
      conducted by Janssen et al. in 1996. Moreover, in 1997, Boardia et al. found that 4g of
      ginger powder was ineffective, where as 10g reduced platelet aggregation. Tested via addition
      of platelet aggregation agonists collagen, ADP, and epinephrine, platelet aggregation was
      inhibited by 35.3%, 37.8%, and 35.9% respectively upon administration of 1g dry ginger for a
      week. A combination of 1 g ginger with 10 mg nifedipine per day could be valuable for
      cardiovascular and cerebrovascular complication due to platelet aggregation.

      Therefore, studies conducted to study the effect of ginger on bleeding risk have found no
      effect up to 15g raw ginger, 40g cooked ginger, or 4g dried ginger daily on platelet
      aggregation whereas 10g of dried ginger decreased platelet aggregation.

      Throughout previous years, several studies have been designed to study the effect of
      different doses of different ginger forms (fresh, dry, extract, capsules) on platelet
      aggregation profile. Although most of them have made the suspect true, still others possess
      controversial results. In view of what literature has offered, it is most probable that
      ginger anti-platelet effect could be dose dependent, form dependent, and probably population
      or individual dependent as postulated by Helgason et al. in 1993 in their analysis of aspirin
      and warfarin platelet aggregation effect. Previous studies might have also employed old,
      non-reliable techniques in studying platelet aggregation profiles. As for the Saudi
      population, consumption of powdered ginger dissolved in hot water is a common practice.
      Accordingly, in this study, it is tempting to speculate the effect of this form of ginger
      consumption, given in separate time points per day, on platelet aggregation profile by using
      platelet aggregation analogues. If positive results were obtained, the herb could provide
      natural protection against the development of platelet aggregation complications and could be
      a potential alternative to aspirin, used for improving blood circulation and hematological
      pathophysiologies in diseased individuals.
    

Intervention name(s): Ginger drink
Intervention type(s): Dietary Supplement
Intervention description(s): Ginger powder dissolved in water
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening