The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 19 No. 7 • December 2016


A recent paper (Borges, 2016) reports that tetrahydrobiopterin levels were significantly increased by green tea in a small study. This suggests an exciting potential benefit of green tea that has not been widely discussed or appreciated.

Patients were randomly assigned to two groups, 21 of which received GTP (green tea polyphenols) containing 800 mg of epigallocatechin gallate (EGCG), while 21 received placebo. Of the 21 receiving green tea, 17 had type 2 diabetes and 4 had type 1 diabetes; the 21 that received placebo had type 2 diabetes. “The beneficial effect of GTP [green tea polyphenols] on albuminuria was maintained even when we included only patients with diabetes mellitus (DM) type 2 in the analyses, resulting in a 37% reduction vs. a 4% increase (p=0.03) for the GTP and placebo groups, respectively [after 12 weeks of treatment].” (Borges, 2016)


By protecting tetrahydrobiopterin from oxidation, green tea may have indirect life extending effects because tetrahydrobiopterin is an important cofactor for the production of nitric oxide from endothelial nitric oxide synthase (eNOS). “That NO [nitric oxide] may extend lifespan has been supported by the relevant observations by Li and colleagues (Li et al, 2011).” Moreover, “it has been reported that eNOS expression is induced, and NO-dependent mitochondrial biogenesis [creation of new mitochondria] is augmented, in the every-other-day feeding model of caloric restriction (CR) in mice.” A 2015 review paper (Valerio, 2015) describes these and some of the other recent research suggesting the possible life-extending effects of nitric oxide.

Tetrahydrobiopterin, the Oxidative Stress Regulator You Probably Never Heard of...And Why You Should

TETRAHYDROBIOPTERIN (BH4) is a key to the regulation of the mitochondrial electron transport chain that produces the cellular energy carrier in the form of ATP. One reason that you probably haven’t heard of tetrahydrobiopterin is that it is not available as a dietary supplement. It cannot be taken orally (check!). In animal experiments, it is administered by injection.

Yet, increasing tetrahydrobiopterin may offer important health benefits. It is great to know, then, that the bioavailability of tetrahydrobiopterin can be significantly increased with EGCG, a common inexpensive dietary supplement.

What are the benefits of tetrahydrobiopterin? A recent paper reports that it “may be useful in treating DN [diabetic nephropathy, the kidney damage that is a frequent complication of diabetes and is also a common cause of death from diabetes], a disease characterized by endothelial dysfunction.” (Faria, 2012, Borges, 2016) (Interestingly, kidneys are not very good at self-repair and their function declines with age. If you live long enough, kidney failure is likely to get you.) But tetrahydrobiopterin does much more than provide protection against kidney damage.


Diabetes is considered a good model of accelerated aging. It is an age-associated disease and the mechanisms that cause it are the same as those causing other age-associated diseases. For example, the endothelial dysfunction that characterizes diabetes also characterizes cardiovascular disease (CVD) and, like diabetes, CVD is the result of the uncoupling of nitric oxide synthase, the enzyme that produces nitric oxide, a gas that regulates the dilation of blood vessels. This uncoupling is what causes nitric oxide synthase to produce superoxide radicals rather than nitric oxide.

A study (Verma, 2002) of the effects of tetrahydrobiopterin administered intravenously in a rat experimental ischemia/reperfusion model restored impaired endothelial function. The authors suggest that “this cofactor [tetrahydrobiopterin, a cofactor for nitric oxide synthase] might exert myocardial protection through prevention of endothelial dysfunction, lipid peroxidation, and direct cardiomyocyte injury.” They note that tetrahydrobiopterin has very low toxicity and can be administered intravenously in high doses. In conclusion, the authors say: “These data underscore the importance of BH4 [tetrahydrobiopterin]...”


“...enzymatic coupling of eNOS by BH4 [tetrahydrobiopterin] plays a critical role in the maintenance of NO bioavailability...” (Faria, 2012)

And here is where TETRAHYDROBIOPTERIN comes in. The uncoupling of nitric oxide synthase is “characterized by a reduction in tetrahydrobiopterin (BH4) levels” and increasing BH4 levels could reverse that uncoupling. (Faria, 2012) One reason for the reduction in tetrahydrobiopterin levels is that it is very sensitive to oxidation. “BH4 [tetrahydrobiopterin] is one of the most potent naturally occurring reducing agents. It is therefore reasonable to hypothesize that oxidative stress may lead to excessive oxidation and depletion of BH4. As oxidative stress occurs in cardiovascular pathophysiology...oxidation of BH4 may be the common cause of eNOS [endothelial nitric oxide synthase] dysfunction...” (Forstermann, 2011) The authors (Forstermann, 2011) note: “Administration of BH4 restored endothelial function in animal models of diabetes and insulin-resistance, as well as in patients with hypercholesterolaemia, diabetes mellitus, essential hypertension, and in chronic smokers.”


We consider EGCG one of the most cost-effective supplements we include in our regimen. In addition to all of the above, EGCG has been found to reactivate methylation-silenced cancer suppressing genes in cancer cell lines (Fang, 2003). Also, vitamin D3 conversion to the biologically active form by certain genes (primarily CYP24A1) is decreased by downregulation of CYP24A1 expression by DNA methylation in prostate cancer cells, resulting in less active vitamin D3. (Deeb, 2011) EGCG may, we believe, reactivate CYP24A1 as has been found in methylation-silenced genes in cancer cells. This might be part of EGCG’s anti-cancer protection.

We get our EGCG from Life Enhancement’s Green Tea Booster EGCG capsules and take one capsule with each meal. Each capsule contains 330 mg of EGCG.


  • Borges et al. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: a double-blind randomised clinical trial. Sci Rep. 6:28282. doi: 10.1038/srep28282 (2016 Jun 20).
  • Bourdon et al. Glucose and free radicals impair the antioxidant properties of serum albumin. FASEB J. 13:233-44 (1999).
  • Deeb et al. Differential vitamin D 24-hydroxylase/CYP24A1 gene promoter methylation in endothelium from benign and malignant human prostate. Epigenetics. 6(8):994-1000 (2011).
  • ­­Fang et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 63:7563-70 (2003).
  • Faria et al. Uncoupling endothelial nitric oxide synt hase is ameliorated by green tea in experimental diabetes by re-establishing tetrahydrobiopterin levels. Diabetes. 61:1838-47 (2012).
  • Forstermann and Li. Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling. Br J Pharmacol. 164:213-23 (2011).
  • Li et al. Identification of potential calorie restriction-mimicking yeast mutants with increased mitochondrial respiratory chain and nitric oxide levels. J Aging Res. 673185, doi: 10.4061/2011/673185 (2011:).
  • Valerio and Nisoli. Nitric oxide, interorganelle communication, and energy flow: a novel route to slow aging. Front Cell Dev Biol. 6;3:6:1-10 (Feb. 2015).
  • Verma et al. Novel cardioprotective effects of tetrahydrobiopterin after anoxia and reoxygenation: Identifying cellular targets for pharmacologic manipulation. J Thorac Cardiovasc Surg. 123:1074-83 (2002).
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