Remember PC-SPES? Here’s what happened…

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PC-SPES was everywhere in the ’90s…it was huge! So why did it suddenly disappear?

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Remember PC-SPES? Here’s what happened…

In 1994, an Asian-American chemist imported a Taiwanese eight-herb combo known as PC-SPES. It seemed like a godsend for men…

Although this stuff was inspired by ancient Chinese medicine, the second half of its name (SPES) comes from the Latin word for “hope.”

The first half (PC) was an acronym for “prostate cancer,” which indicates its suggested use.

During the 1990s, this eight-herb combo progressively gained notoriety on the internet.

Eventually, there was so much interest that scientists and physicians felt compelled to study it.

Invariably, PC-SPES was shown to be quite effective at reducing cell proliferation, tumor volume, and PSA levels.

And it got more popular by the minute because published science was constantly substantiating its effects.

And from that point on it was doomed.

The PC-SPES brand became too effective and popular for the AMA and Big Pharma to just sit back and watch it take their market share.

If they couldn’t find some obscure legal technicality to hang it on, they’d just have to invent one.

And so they did… well, maybe.

It seems that what finally sank PC-SPES may have been a mix of AMA-contrived data and self-inflicted adulteration.

There had been reports before then of substantial estrogenic activity residing in PC-SPES, no doubt originating from DES-like compounds found within.

(DES – diethylstilbestrol – is an estrogen medication not in use much anymore.)

This came as no real surprise to its users with gynecomastia, one of PC-SPES’s more common side effects occurring in roughly 8.7% of users (gynecomastia = man boobs).

Although PC-SPES does contain reishi mushroom that could account for its estrogenic activity, the guillotine was effectively dropped on PC-SPES with this graphic (Sovac, 2002):

This convincing juxtaposition of magnetic resonance and mass spectroscopic profiles (“fingerprints”) assured doctors and scientists across the globe:

See, now, people? Only synthetic chemicals can lower PSA levels by 50%. All natural treatments are pixie dust by comparison. AND indomethacin and DES were responsible for all the problems with PC-SPES.

And yet…

A study published four years earlier in the high-impact New England Medical Journal had found only DES-like compounds, not DES proper.

Many plants make stilbenoids and some are very similar in form to diethylstilbestrol (DES).

And even more suspiciously…

Scientists found the highest “DES” concentrations in PC-SPES in 1998 – the same year that the DES-like compound was shown to be quite different from DES itself:

It’s not like they had a motive to make PC-SPES any more estrogenic than it already was.

This product contained reishi mushrooms, fully capable of increasing uterine weights in rats and causing full-blown gyno all on its own.

“The action of the ethanol extract of reishi mushroom in MCF-7 can be specifically blocked by treating with an ER antagonist…The ethanol extract of reishi mushroom activated transcription of the pS2 gene. These data confirm that the ethanol extract of reishi mushroom can act as an estrogen receptor agonist.”

(The pS2 gene is associated with breast cancer and estrogen.)

Besides being the most estrogenic shroom on the planet, the reishi also inhibits 5α-reductase more than anything.

(5α-reductase is an enzyme involved in androgen and estrogen metabolism.)

The apparition of DES exactly at the same time that the popularity of PC-SPES was exploding seems a bit too convenient – even suggestive of malfeasance.

They also found indomethacin in PC-SPES.

(Indomethacin is an anti-inflammatory drug that inhibits prostaglandin.)

So that probably helped to convince doctors that “only synthetic drugs can lower prostaglandin E2.”

Yet the Isatis indigotica leaf in PC-SPES produces very similar molecules, some of which haven’t been fully characterized.

Isatis indigotica is heavy in indoles. It is the same plant indigo dye comes from.

This plant produces more indole derivatives than any other, and some of them are superficially similar to indomethacin (the prostaglandin inhibitor mentioned above).

But there is more…

They also “found” warfarin in PC-SPES.

Now, including something like that actually makes some sense.

That’s because blood clotting is a side effect of heavy estrogen use and, as I said above, there are estrogen-like compounds in PC-SPES.

And there had been reports of venous thrombosis in PC-SPES users.

And case reports of bleeding, the classic effect of warfarin, have also been published in relation to PC-SPES users.

It’s almost as if BotanicLab (the maker of PC-SPES) knew about the blood clotting and threw in warfarin as a precaution.

But if that is the deal, you would think they would have chosen red clover instead.

Clover contains dicoumarol, the natural compound that warfarin is based on.

Warfarin is merely a synthetic spin-off of dicoumarol, a molecule discovered in pursuit of finding out why some Wisconsin cows bled to death in the 1920s.

Maybe they intentionally adulterated PC-SPES to compensate for its flaws, maybe it was frame job. Maybe both.

I am not interested in defending PC-SPES in any way.

This stuff was a product designed to inhibit prostate cancer – at the expense of sprouting man boobs.

And BotanicLab didn’t even have the common courtesy of including a free bra with the tenth purchase – the least they could have done for $108 per bottle.

Yet PC-SPES actually did work… That much is certain.

Dozens of scientific publications of all types ranging from prospective trials to rat studies have consistently verified that.

After the untimely death of PC-SPES in 2002, this study set out to discover what was responsible for its anti-cancer activity by doing a postmortem on old lots of it:

Michael Bonham’s look into the substantial antineoplastic activity of PC-SPES took place between 2002 and 2005.

Purpose: Botanical preparations are widely used by patients with prostate cancer. Scutellaria baicalensis, a botanical with a long history of medicinal use in China, was a constituent of the herbal mixture PC-SPES, a product that inhibited prostate cancer growth in both laboratory and clinical studies.”

“Due to the difficulties encountered when evaluating the efficacy of complex natural products, we sought to identify active chemical constituents within Scutellaria and determine their mechanisms of action.”

It was already obvious what had caused the man boobs…

Ginseng root and reishi mushrooms were implicated and then convicted of conspiring together in C-cup synergy.

Micheal Bohnam’s earlier studies had been just some of many that confirmed the substantial anti-tumor activity of PC-SPES.

So this newer study of his wasn’t unique in that respect.

But in this study, he took it upon himself to test extracts of all eight herbs individually.

All but ginseng, that is, which was “not available” – ostensibly due to its price and unpredictable natural occurrence.

So he tested seven of the herbs.

Out of those, he found Scutellaria baicalensis to have the most profound anti-tumor activity.

For this reason, he decided to focus on that one alone.

“Given these results, we chose to focus on identifying active compounds in extracts of S. baicalensis.”

He had then fractionated the S. baicalensis extract and found the anti-tumor activity in two fractions, one of which was entirely baicalein.

In the other fraction, he found three methylated baicalein near-relatives with crazy names:

Wogonin, neobaicalein, and skullcapflavone.

Although perhaps a bit more lipophilic and cell-permeable than the pure baicalein in the other fraction, these three never amount to even half of the plant’s composition of baicalein.

In addition, besides their relative scarcity, these three did not perform quite as well as pure baicalein in equal concentrations.

Baicalein was the most effective anti-tumor agent of S. baicalensis, this being the most effective anti-tumor herb found in PC-SPES.

“The most abundant active compound in the S. baicalensis extract was determined to be baicalein – and most, although not all, of the activity seen with the complete extract could be attributed to this single compound.”

And baicalein does not give people manboobs, not even a B-cup.

This makes me wonder why BotanicLab didn’t just use S. baicalensis without all these other compounds.

Michael Bohnam then force-fed cancerous rodents with baicalein (in oil), while making a control group do without.

And he watched as baicalein substantially delayed the progression of tumor growth:

Baicalein delayed the doubling time of tumor volume by a factor of 4.1, going from 7.8 days in the control group to 32 days in the baicalein group.

Baicalein also more than doubled the survival rate, despite the corn oil the rodents had been force-fed.

“Once tumors reached 250 mm3, treatment was initiated. Animals were then supplemented by gavage (tube-feeding) with control vehicle oil (corn oil/safflower oil/olive oil) or baicalein 20 mg/kg/d in oil.”

Baicalein also significantly reduced PSA at a concentration of 30 μM, explaining the consistent 50% reductions previously observed in patients taking PC-SPES.

This same effect was replicated in 2007 by Asian-American scientist Fei Ye in the same cell type, also showing a massive reduction of PSA synthesis using a S. baicalensis extract:

In addition, Fei Ye confirmed delayed tumor growth using the same mouse type.

But he used a whole-plant extract of S. baicalensis and not pure baicalein.

And since his mice hadn’t been force-fed corn oil, their tumors barely grew at all:

He compared the S. baicalensis plant extract directly against PC-SPES, with all of its eight herbs.

He found S. baicalensis extract to be more effective than the same weight of PC-SPES extract.

“S. baicalensis was more effective in the inhibition of cell growth compared with PC-SPES (IC50 = 0.38 mg/ml for PC-3 cells).”

His extract reduced prostaglandin E2 production by about half (nearly as well as 25 µM celecoxib).

Many other studies verify the ability of S. baicalensis to lower prostaglandin E2 production in cells.

These effects are significant and consistent – and purified baicalein could rightly compete against indomethacin gram for gram.

Sure, PC-SPES probably did need some warfarin or dicoumarol to counter that blood-clotting issue caused by estrogen…

But it certainly didn’t actually need any help from indomethacin – because PC-SPES contained enough baicalein (from S. baicalensis) to make indomethacin unnecessary.

Turns out, baicalein is a powerful glyoxalase I inhibitor (induces death of tumor cells).

Baicalein causes a sea-change within the cell by increasing its methylglyoxal levels.

And that affects every enzyme and receptor that had evolved to respond to it (including carbonic anhydrase, 12-lipoxygenase, and cyclooxygenase).

“Treatment-related toxicities were not observed in the mice receiving baicalein.”

It’s true that baicalein prevents androgen binding, to an extent, through methylglyoxal modification, but it inhibits the estrogen receptor just the same.

Due to the similarity of sex steroid receptors with others, you would expect that baicalein would inhibit the glucocorticoid and mineralocorticoid receptors in the same manner.

So baicalein and its parent plant can hardly be considered specific “antiandrogens” – and most certainly not “estrogenic.”

Baicalein is more a general inhibitor of steroid receptor activation, an effect mediated through methylglyoxal.

“None of the four compounds produced measurable decreases in [androgen receptor protein levels at these concentrations and time points analyzed. However, PSA protein levels were decreased by each compound at 24 hours.”

Baicalein has very little effect on androgen receptor expression, and absolutely no effect on steroid hormone concentrations.

Baicalein is a glyoxalase I inhibitor capable of increasing methylglyoxal throughout the entire cell.

And that is why it has such extensive and seemingly unrelated effects.

Methylglyoxal is a known anti-tumor agent that has been suppressed ever since the 1930s, around the time Robert Koch, founder of modern bacteriology, began using it to cure cancer.

“At a false discovery rate of 1.25%, S. baicalensis extract altered the expression of 1,645 transcripts – and the four-compound combination of baicalein, neobaicalein, skullcapflavone, and wogonin altered the expression of 446 transcripts in LNCaP cells after 24 hours of treatment.”

(LNCaP cells are androgen-sensitive human prostate cancer cells.)

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Ye, Fei. "Molecular mechanism of anti-prostate cancer activity of Scutellaria baicalensis extract." Nutrition and cancer (2007) http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.474.5973&rep=rep1&type=pdf   Bonham, M. "Characterization of chemical constituents in S. baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma." Clinical Cancer Research (2005) http://clincancerres.aacrjournals.org/content/clincanres/11/10/3905.full.pdf   Zhang, David. "Inhibition of cancer cell proliferation and PGE2 synthesis by S. baicalensis." Cancer Research (2003) http://cancerres.aacrjournals.org/content/canres/63/14/4037.full.pdf   Sovak, Milos. "Herbal composition PC-SPES for management of prostate cancer: identification of active principles." Journal of the National Cancer Institute (2002) https://www.ncbi.nlm.nih.gov/pubmed/12208892   DiPaola, Robert. "Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer." New England Journal of Medicine (1998) http://www.usrf.org/news/PC-SPES_DiPaola_98NEJM.pdf