The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 17 No. 9 • October 2014


PLATELETS CRUCIAL FOR EARLY METASTASIS IN CANCER

Taurine Regulates the Sensitivity of Platelets to Aggregation

Taurine May Help Protect Against Metastasis

As we wrote in the last issue of this newsletter, taurine was found in a human study to increase the resistance of platelets to aggregation by 30% or 70% in response to supplementation with extra taurine (beyond ordinary adequate dietary amounts) of 1400 mg/day or 1600 mg/day, respectively.1 We have followed up that intriguing result and have found out more on taurine’s effects on platelets, as well as the latest research findings on the crucial role of platelets in establishing early metastatic niches for circulating cancer cells.

Inflammation and Coagulation May Be Parts of the Same Process

As we further noted in our article in the last Durk & Sandy newsletter, increased inflammation has been proposed to be derived from increasing activation of the coagulation system with age, as both inflammation and coagulation share many components and have strong interactions. “The increased hypercoagulable state observed with aging may account for the higher incidence of arterial and venous thrombosis in the elderly persons.”2 Moreover, the increased coagulability may also be a factor in the increasing susceptibility of elderly persons to develop cancer.

Platelet Sensitivity to Aggregation in Cats and Humans: Stabilized by Taurine

The paper mentioned in paragraph #1 above reported that taurine had a significant effect in decreasing the sensitivity of platelets to aggregation in both cats and humans. The taurine-deficiency condition in cats, a form of heart failure, is often complicated by systemic arterial thromboembolism. Platelets in vitro treated with taurine are stabilized against a variety of aggregating agents. The human study showed taurine supplementation increased the threshold level of collagen required to stimulate platelet aggregation and that the platelets released less TXB2 (thromboxane).1

Resistance to Clot Formation in Hibernating Animals May Be Due to Taurine

A study2B on the unusual subject of how taurine acts to prevent clots from forming under conditions of very slow blood flow and increased blood viscosity brought about by low body temperature contributes to our understanding of taurine’s effects on platelets. First, hibernating animals were reported to accumulate by 2.25-fold their amino acid pool, with taurine accounting for 52% of that. Taurine was shown to prolong coagulation time in donor plasma with taurine increasing platelet aggregation to thrombin at taurine’s highest concentration (25 mM) by 9%. The result was significant yet maintained the thrombin time within normal limits. At 5 mM, taurine inhibited platelet aggregation by 10%. There was essentially no difference in the ability of taurine to prevent excessive platelet aggregation (without preventing normal platelet aggregation) over a 500% serum concentration range. This is very different from prescription anti-platelet drugs, which typically have a very narrow therapeutic window. If you took five times the prescribed dose of these anticoagulation drugs you would be in serious danger of bleeding to death.

Taurine Chloramine and Taurine Bromamine Are Also Anticoagulants

As reported in another paper,2C taurine chloramine, the reaction product of taurine and hypochlorous acid (the latter released by the enzyme myeloperoxidase in the presence of chloride ion) is able to kill a variety of pathogens, including bacteria, fungi, viruses, protozoa, as well as degrading biofilms and also is anti-inflammatory and anticoagulant. Taurine bromamine, the reaction product of taurine and hypobromous acid (released by myeloperoxidase in the presence of bromide ion) has similar effects to taurine chloramine.

Platelets’ Important Involvement in Establishing Early Metastatic Niches

A new paper3 reports on a close relationship between platelets and tumor cells, including the early establishment of metastatic niches. As the paper explains, there are a number of mechanisms involved. For example, direct contact between tumor cells and platelets is reported to induce signaling through the transforming growth factor beta (TGFbeta1) and NFkappaB signaling pathways in tumor cells that induces a process called the epithelial-­mesenchymal transition, which is important in carcinogenesis and promoting metastasis. In early metastasis, platelets “recruit” granulocytes in the bloodstream via the release by the platelets of certain chemokines.

The researchers used a very clever technique for following metastasis from its inception: injecting tumor cells into the lungs of mice and examining in detail what took place during the first few minutes to hours of the ensuing process. Platelet aggregates surrounding tumor cells were observed after only one minute following the injection of the tumor cells. Granulocytes were recruited to the platelet-tumor cell aggregates over the next 30 minutes. Granulocyte-depleting antibodies could, in a single dose, result in fewer metastases. Similarly, platelet depletion was even more potent in inhibiting tumor cell seeding, almost completely eliminating it after 48 hours. The researchers report that recent clinical studies have shown that high levels of CXCL5, a chemokine released by platelets, and elevated numbers of circulating granulocytes are independent predictors of disease progression and poor prognosis for patients.

Taurine Content of Platelets Is Extraordinarily High

According to an early paper,4 normal human blood platelets contain more taurine than any other amino acid and, remarkably, increase taurine uptake against a concentration gradient of 440:1 (!) Unsurprisingly, taurine is actively transported (the process requires the expenditure of energy), as it would hardly do so otherwise against such a high concentration gradient. Clearly, taurine is important for platelet function to justify this metabolically expensive process.

CONCLUSION: Taurine May Help Combat Metastasis
CONCLUSION: Taurine May Be Useful In Preventing Blood Clots in Those At Risk

We conclude that taurine may act to reduce the likelihood of early metastatic processes established by the activity of platelets and that taurine may, therefore, be useful as part of cancer prevention and even as part of cancer therapy. We conclude, as well, that taurine may be a useful therapy for people who are at risk of abnormal blood clots. For those with such a problem who have been prescribed Coumadin, an anticoagulant, note that Coumadin has a very small therapeutic index (the ratio between the therapeutic dose and the toxic dose). You might want to talk to your physician about increasing your intake of taurine and possibly decreasing your dose of Coumadin, but be sure to get your physician’s advice before doing this. He or she will have a far better understanding of the specifics of your case (because he or she can measure your platelet aggregation and coagulation) than we can have (since we are scientists, not physicians, and don’t know about your medical situation at all).

Suggested Daily Dose of OUR Taurine and Bromine Formulation Supplies 3,000 mg Taurine (as Two Divided Doses)

We are both taking the suggested daily dose of our new Taurine and Bromine formulation. As we had noted previously, Sandy has noticed significant improvement in her painful knee osteoarthritis with it. (This effect probably has nothing to do with platelet aggregation but may be due to the powerful anti-inflammatory effects of taurine chloramine and taurine bromamine, which are naturally formed in your body.) For even more information on our Taurine and Bromine Formulation, see the last issue of this newsletter for much more data and additional references.

Antiplatelet Effects of Allyl Isothiocyanate, a Major Component of Mustard

A new paper5 claims to be the first attempt to evaluate the effect of allyl isothiocyanate (AITC), a major constituent of mustard, on platelet aggregation. AITC is the source of the pungent flavor of mustard and studies have reported anti-inflammatory and antitumor effects of the compound. The effect of AITC on platelet aggregation and on thromboembolism in mice, rats, and humans were investigated. Platelet aggregation on rat platelets in vitro as induced by collagen, thrombin, adenosine diphosphate (ADP), and arachidonic acid (AA) were significantly inhibited by either 100 or 300 μM AITC, indicating that allyl isothiocyanate can suppress platelet aggregation by a number of different aggregation-inducing stimuli. The researchers also used the acute pulmonary thromboembolism mouse model to evaluate the protective effect of AITC in this commonly used model. Oral administration of 3 mg/kg AITC had a protective effect against pulmonary thrombo­embolism mortality, reducing it by 63%. AITC was also effective in inhibiting platelet aggregation in human PRP (platelet rich plasma) induced by collagen, thrombin, ADP, and AA, reducing the release by platelets of thromboxane2. The authors conclude that their data suggest that AITC has “remarkable antiplatelet effects and maybe a therapeutic potential for the prevention of aberrant platelet activation-related disorders.”5 So, slather mustard on your reduced fat hot dog and enjoy!

References

1. Hayes, Pronczuk, et al. Taurine modulates platelet aggregation in cats and humans. Am J Clin Nutr. 49:1211–6 (1989).
2. Xu, Ameja, Tappia, et al. The potential health benefits of taurine in cardiovascular disease. Exp Clin Cardiol. 13(2):57–65 (2008).
2B. Miglis, Wilder, et al. Effect of taurine on platelets and the plasma coagulation system. Platelets. 13:5–10 (2002).
2C. Gottardi et al. N-chloramines, a promising class of well-tolerated topical anti-infectives. Antimicrob Agents Chemother. 57(3):1107–14 (2013).
3. Labelle et al. Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci U S A. [publ. online July 14, 2014]:E3053–61.
4. Ahtee et al. Transport of taurine by normal blood platelets. Br J Pharmacol. 52:245–51 (1974)
5. Lee, Kim, Jung. Inhibitory effect of allyl isothiocyanate on platelet aggregation. J Agric Food Chem. 62:7131–9 (2014).

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