Histamines and Anticoagulants – a review

A good friend is testing the excessive histamine model as a significant vector for CFS. This model does fit with the dysfunctional microbiome model because gut bacteria changes histidine into histamine. The friend is showing significant signs of improvement (with a lot of symptom changes).

I was asked to double check my usual list of anti-coagulants against histamine influence. These are notes that I extracted my reference book and PubMed  review. There are three supplements that appear to reduce histamine levels, improve cognitive function and reduce coagulation (thick blood):

  • Alpha Lipoic Acid
  • Turmeric
  • Vitamin D3


In CFS patients this is important because it impacts cognitive function:

  • Relatively high in occipital cortex of the brain
  • Abnormally high in general
  • Improves with viral clearance, resulting in significant improvements in verbal learning, memory, and visual-spatial memory
  • Normalizes with Turmeric (curcumin – reduces histamine levels [2014] [2013])
  • Normalizes with Alpha Lipoic Acid (reduces histamine levels [2010] [2010])

Alpha Lipoic Acid

  • Decreases CD62P platelet expression
  • Decreases CRP levels by 19%
  • Decreases fibrinogen, factor VII, vWF, and triglycerides
  • Decreases plasma levels of free fatty acids, triglyceride, total cholesterol, low density lipoprotein-cholesterol, small dense LDL-cholesterol, oxidized LDL-cholesterol, very low density lipoprotein-cholesterol
  • Decreases symptoms of neuropathy and neuropathic deficit
  • Decreases TNF, IL-6
  • Improves blood flow and nerve function


The active ingredient of this kitchen spice is curcumin. Turmeric may be more effective than curcumin, the extract. Curcumin has anti-inflammatory, anti-oxidant, pro-apoptotic, chemo preventive, chemotherapeutic, anti-proliferative, wound healing, anti-parasitic, anti-malarial and anti-bacterial activity. Although inexpensive, apparently well tolerated and potentially active, curcumin has not been approved for the treatment of any human disease.

  • Benefits IBS
  • Bioactivity is increased by adding 1% black pepper
  • Increases fibrinolytic activity
  • Inhibits platelet aggregation, increases coagulation time
  • Inhibits EBV, antiviral
  • Inhibits H. pylori
  • Inhibits inducible nitric oxide synthase (iNOS)
  • Neuroprotective
  • Reduces high level of fibrinogen
  • Reduces IL6, IL8, TNF

Vitamin D3

  • 22% – 65% of CFS patients are deficient (less than 20 ng/mL)
  • 61% – 80% of Fibromyalgia patients are deficient (less than 20 ng/mL)
  • Associated with headaches, hypersomnia
  • Associated with orthostatic intolerance
  • Hypersomnia eliminated with supplements
  • Improvement became more significant with FM when blood level of 25(OH) D exceeded 50 ng/ mL (125 nmol/L)
  • Moderately to severely sub-optimal in CFS patients
  • Remission seen with 2000–10000 IU/day (with magnesium and phosphate)
  • Treatment with high-dose vitamin D resulted in clinical improvement in all FM patients
  • With myalgia in statin-treated patients, 92% were resolved when levels reached 50 ng/mL (125 nmol/L)
  • Patients with 25-OHD less than 20 ng/ml (50 nmol/L) are more likely to have
    • impaired short memory
    • confusion
    • mood disturbance
    • sleep disturbance
    • restless leg syndrome
    • palpitation
  • Inhibits  thrombus formation [2014]
  • Attenuates platelet activation  [2011]
  • Low levels seen with antiphospholipid syndrome (APS) with thrombotic disease[2012]  (a variation of APS is Dave Berg’s Hemex model of CFS)
  • Reduces histamine levels [1996] [1995] [2014]
  • A dosage to discuss with you health profession may be 15,000 to 20,000 IU/day for a few months.

To Be Avoided Anticoagulants


  • “aspirin enhanced histamine release” [2013]


  • AVOID:  allergic reaction is known to happen with this [nih] – which implies histamine release.

Other  OTC anti-coagulants


  • Anti-inflammatory
  • Effective for inflammatory venous disease
  • Improves antibiotic concentration up to 850%
  • Inhibits the formation of biofilms
  • No information on Histamine or Mast Cell impact


  • Anti-hypertensive
  • Cleaves cross-linked fibrin
  • Decreases red blood cell aggregation and shear-viscosity of blood cells
  • Inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity
  • Increases activated factor VII levels
  • No information on Histamine or Mast Cell impact


  • Anti-thrombotic
  • Digests fibrinogen and inhibits platelet adhesion
  • Decreases fibrinogen significantly. Inhibition of intrinsic coagulation pathway and the activation of fibrinolysis via an increase of t-PA activity
  • No information on Histamine or Mast Cell impact

Grape Seed Extract

Grape seed extract is rich in proanthocyanidins. Proanthocyanidins are available from other supplements (cranberry juice, cider). There are contradictory reports on whether it increases or decreases IL6, IL8, TNF. It may or may not offer protection for glutamate excitotoxicity (depends on grapes being used)

  • Decrease in uPA and PAI-1 activities and thus decreased fibrinolytic activity
  • Decreased fibrinolytic activity, decreased cell-surface plasmin activity
  • Decreases fatigue when taken with L-arginine
  • Decreases COX2
  • Decreases fatigue
  • Decreases IL-17, IL-6
  • Decreases IL-1-beta,TNF, IL-6 and IL-8
  • Decreases platelet activation
  • Decreases thrombus formation, inhibitory effect on platelets
  • Increases anti-thrombin activity
  • Increases TNF
  • No information on Histamine or Mast Cell impact.
    • Because it is a salicylate (like aspirin and bromelain) – probably best to avoid