St. John's Wort: Not sure what it should be standardized to, Hyperforin or Hypericin; possible flaw with some studies

From http://altmedicine.about.com/cs/anxietydepression/a/SJW.htm:

Regarding a study published in JAMA saying St. John's Wort is not effective for major depression:

"The 200 subjects in the study were randomly divided into two groups. One group received a 300 mg tablet extract of St. John's Wort and the other group received an identically matched placebo for an eight week treatment period. Both groups were instructed to take one tablet three times per day.

After four weeks, the dose of St. John's Wort or placebo was increased to four tablets per day for the remainder of the study if the subject had not shown improvement. The researchers concluded that St. John's wort was not effective for the treatment of major depression."

However, some important caveats:

The dose may have been too small - 900 mg/day is the standard dose for mild to moderate depression, so perhaps more than 900 to 1200 mg was needed for major depression.

Also:

"Another possible issue with this study is that St. John's wort extracts used in this study were standardized to an ingredient called hypericin. The process of standardization is for quality assurance. It's a guarantee that a specified amount of an ingredient (presumably the medicinally active ingredient) is present in the herbal extract. The PDR for Herbal Medicine, a respected herbal reference, states that hyperforin and not hypericin may be the primary active ingredient for treating depression.

In another study, patients received either placebo, a St. John's Wort extract standardized to 0.5% hyperforin, or a St. John's Wort extract standardized to 5% hyperforin. Only patients who received the extract of 5% hyperforin showed significant improvement of depressive symptoms."

However, most of the successful clinical trials used extract standardized to Hypericin. From http://cms.herbalgram.org/herbalmedicine/StJohn27swort.html:

"Since 1979, there have been about 30 controlled trials with Hypericum extracts, involving thousands of patients with mild to moderate depressive disorders. Most studies lasted 28 to 42 days with daily dosages of 900 mg of an extract standardized to 0.3% hypericin (Jarsin^®, LI 160, Lichtwer Pharma, Berlin). Up to 1997, there have been at least 15 controlled studies on a methanolic extract of SJW (LI 160) and 12 controlled studies on four additional preparations made from ethanolic extracts of SJW (Schulz et al., 1998). They have confirmed the antidepressant action of SJW extracts in humans (Bombardelli and Morazzoni, 1995; Linde et al., 1996; Reuter, 1998; Upton, 1997)."

But, perhaps there is one more twist that supports Hyperforin, after all:

"Other experimental studies have also shown the relevance of hyperforin (Chatterjee et al., 1998; Bhattacharya et al., 1998). However, additional animal and human research is being conducted to clarify the importance of hyperforin, since most of the studies on St. John's wort were conducted on preparations standardized to hypericin, not hyperforin, content [This is what we just pointed out]. Nevertheless, a representative of the leading manufacturer of the most clinically tested hypericin-based SJW extract (i.e., LI 160 from Lichtwer Pharma) has written that this product showed hyperforin levels of 1% to 6% upon analysis; new studies by Lichtwer on LI 160 will be carried out on an extract standardized to hyperforin values of approximately 4% (Schulz, 1998)."

So, maybe hyperforin was the active ingredient all along.