Estimated Therapeutic and Loael Doses of Isoflavones Flavones and Flavonols

The estimated required doses as scaled from animal antitumor studies (and anti-inflammatory studies) reasonably agree with estimated doses calculated from pharmacokinetic and in-vitro data. The required dose scaled from animal antitumor studies ranges from 250 milligrams to 9.9 grams, and that based on pharmacoki-netic calculations is similar. Using a target in-vivo concentration of 15 mM for each compound (30 pM after adjustment for conjugates; see Appendix J), the required dose ranges from 720 milligrams to 5.2 grams. We can estimate target human doses by using an average of the doses scaled from animal studies and those calculated from pharmacokinetic and in-vitro data. For all compounds, the target doses are below the LOAEL doses.

The therapeutic dose estimates are summarized in Table 19.3. For all four flavonoids, the low end of the tentative recommended dose range is equal to the dose calculated by assuming a full 15-fold increase in potency by synergistic interactions. For genistein, the high end of the tentative recommended dose range is equal to the estimated LOAEL dose for daidzein; these two isoflavones normally occur in about 1 to 1 ratios in most soy-based genistein products, and the estimated LOAEL dose for daidzein is lower than for genistein. For api-genin, the high end of the tentative recommended dose range is equal to the target dose of 1.5 grams. For luteo-lin and quercetin, the high end of the tentative recommended dose range is equal to the assumed general linear bioavailability limit of 1.8 grams per day (see Appendix J). Higher doses, up to the estimated LOAEL dose, could be used, but it is uncertain whether they would be fully absorbed or would produce metabolites similar to those achieved by the lower doses.

It appears that synergistic interactions may be required for genistein, luteolin, and quercetin to produce an anticancer effect in humans. In comparing the target doses listed in Table 19.3 to the maximum tentative recommended doses, synergistic interactions will be needed to generate a minimum 1.4-fold, 1.4-fold, and 2.1-fold increase in potency, respectively. This should be possible, since these required increases are well below the allowable 15-fold increase discussed in Chapter 13.

The actual dose necessary to reach a desired plasma concentration (and its effect) will vary depending on many factors. These include the type of sugars that comprise the glycosides, the length of exposure to the flavonoid, and the individual's sex and particular gut microflora.100104 Nonetheless, the above dose calculations are useful in preliminary estimates. These estimates are for ingestion of the aglycone, and the doses of products containing glycosides would need to be increased about 1.6-fold (since the molecular weights of flavonoid glycosides are generally about 1.6-fold greater than that of the aglycones).

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Cure Tennis Elbow Without Surgery

Cure Tennis Elbow Without Surgery

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