Dr. Ron’s Research Review – January 23, 2013

This week’s research review focuses on Glycine for BPH

In a controlled clinical investigation of benign prostatic hypertrophy, a course of medication containing a mixture of amino acids (Glycine, Alanine and Glutamic Acid) was found to be effective in reducing the size of the prostate and relieving the associated symptoms of discomfort, nocturia, delayed micturition, frequent urination and urgency.  (Feinblatt and Gant 1958)

Amino Acid

Placebo

Enlargement reduced

92%

5%

Restored to normal size

33%

0

Nocturia relieved

95%

15%

Nocturia relieved completely

72%

5%

Urgent urination relieved

81%

11%

Frequency urination relieved

73%

15%

Discomfort relieved

71%

9%

Delayed micturation relieved

70%

4%

A controlled study of 45 cases of uncomplicated BPH has confirmed the original report of Feinblatt and Gant. (Damrau 1962)

Recent research shows that glycine inhibits angiogenesis. (Amin, Li et al. 2003) (Yamashina, Ikejima et al. 2007)

Dr. Ron


Articles

Dietary glycine inhibits angiogenesis during wound healing and tumor growth

            (Amin, Li et al. 2003) Download

In this study we investigated the effects of glycine on angiogenesis during embryogenesis, wound healing and tumor growth. In chorioallantoic membrane (CAM) assay, glycine (100 microM) inhibited angiogenesis by more than 50%. We studied dietary glycine's effect on fibrin induced wound healing response in a novel (Fibrin Z-chamber) assay. Fibrin within the chamber triggers the healing cascade leading to formation of granulation tissue (GT) rich in blood vessels and stroma. GT was reduced by more than 30% (p < 0.0001) in dietary Glycine groups as compared to control. We found that microvessel density dropped significantly (15%, p < 0.0003) with dietary glycine whereas the other components of GT were unaffected. We evaluated tumor growth delay utilizing Tumor Z-Chamber (fibrin with R3230 mammary adenocarcinoma cells) since tumors take advantage of angiogenesis and matrix formation. We observed that tumor growth decreased by 15% (p < 0.03) and tumor microvessel density dropped by 20% (p < 0.03) with dietary glycine compared to controls. We found that iNOS protein levels were decreased significantly in both GT (24%-57%) and tumor tissue (19-75%). In conclusion, we found that dietary glycine is a potent anti-angiogenic agent that can reduce wound healing and tumor growth through reduction of iNOS expression.

Benign prostatic hypertrophy: amino acid therapy for symptomatic relief

            (Damrau 1962) Download

Palliative treatment of benign prostatic hypertrophy; value of glycine-alanine-glutamic acid combination

            (Feinblatt and Gant 1958) Download

In a controlled clinical investigation of benign prostatic hypertrophy, a course of medication containing a mixture of amino acids (Glycine, Alanine and Glutamic Acid) was found to be effective in reducing the size of the prostate and relieving the associated symptoms of discomfort, nocturia, delayed micturition, frequent urination and urgency. As compared with the controls, the results are statistically significant. The value of the Glycine-Alanine-Glutamic Acid mixture for relief of symptoms of benign prostatic hypertrophy was suggested by a chance observation made by one of us (J.C.G.)(1) and an associate. A group of allergic patients were being given an amino acid mixture and during the course of treatment one of the patients volunteered the information that all of his urinary symptoms had disappeared. This led to a trial of that particular amino acid mixture in non-allergic patients with urinary symptoms. Patients with enlarged prostates and associated urinary symptoms experienced prompt and rather spectacular relief of their symptoms. A number of these patients have been observed over a prolonged period of time. They remain symptom free while taking the medication, but soon after discontinuing it the symptoms of urgency, nocturia, etc., returned. This has been the experience of several physicians who have tried the amino acid treatment at our suggestion.

Glycine as a potent anti-angiogenic nutrient for tumor growth

         (Yamashina, Ikejima et al. 2007) Download

Accumulating lines of evidence suggest a possibility that glycine is useful as an immuno-modulating amino acid. Glycine most likely prevents the lipopolysaccharide (LPS)-induced elevation of intracellular Ca(2+) concentration in Kupffer cells, thereby minimizing LPS receptor signaling and cytokine production. Moreover, it was reported that dietary glycine inhibits the growth of tumors. Vascular endothelial growth factor (VEGF) plays a critical role in cancer progression by promoting new blood vessel formation. Activation of VEGF receptor has been shown to result in activation of phospholipase C-gamma and increases in intracellular Ca(2+) concentration. The VEGF-induced cell proliferation is dependent on intracellular Ca(2+) concentration. The effects of glycine on VEGF-induced increases in intracellular Ca(2+) concentration in endothelial cell line (CPA) were studied. The VEGF increased intracellular Ca(2+) concentration rapidly, but glycine blunted increases in intracellular Ca(2+) concentration due to VEGF. Further, the inhibitory effects of glycine were prevented by low concentrations of strychnine (1 micromol/L) or incubation with chloride-free buffer. Moreover, glycine increased influx of radiolabeled chloride into CPA cells approximately 10-fold. Furthermore, mRNA 92% identical to the beta-subunit of the glycine-gated chloride channel from spinal cord was identified in endothelial cells using reverse transcription-polymerase chain reaction. Finally, glycine significantly diminished serum-stimulated proliferation and migration of endothelial cells. These data indicate that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated chloride channel. This hyperpolarizes the cell membrane and blocks influx of Ca(2+), thereby minimizing growth factor-mediated signaling. Therefore, glycine can be used not only for treatment of inflammation, but also for chemoprevention and treatment of carcinoma.

References

Amin, K., J. Li, et al. (2003). "Dietary glycine inhibits angiogenesis during wound healing and tumor growth." Cancer Biol Ther 2(2): 173-8 PMID: 12750558

Damrau, F. (1962). "Benign prostatic hypertrophy: amino acid therapy for symptomatic relief." J Am Geriatr Soc 10: 426-30 PMID: 13883328

Feinblatt, H. M. and J. C. Gant (1958). "Palliative treatment of benign prostatic hypertrophy; value of glycine-alanine-glutamic acid combination." J Maine Med Assoc 49(3): 99-101 passim PMID: 13514330

Yamashina, S., K. Ikejima, et al. (2007). "Glycine as a potent anti-angiogenic nutrient for tumor growth." J Gastroenterol Hepatol 22 Suppl 1: S62-4 PMID: 17567469