Longvida contains only 80 mg curcumin in 500 mg pills, and a paper suggests 8 per day. That's 640 mg per day, about $5 per day. Longvida says it is 68 times more bioavailable, presumably in plasma. The patent says tetrahydrocurcumin is 7 to 8 times more bioavailable than curcumin and it costs only $0.50 per 1000 mg on alibaba. The patent says mixing with 1:1 with curcumin, 10:1 vitamin C, olive oil, and pepper improves upon this. Tetrahydrocurcumin is more bioavailable in the blood, but not brain, so there are reasons you have to mix it with curcumin. Also it would be good if you can esterify a fatty acid or other acyl group. Then their is their "lipid micelles and microencapsulated oils" procedures.
If you can't esterify or microencapsulate, then the tetra:curcumin, vit C, oil, pepper mixture may give only 10 times more than curcumin, which is 7 times less than longvida and cost 20 times less. Instead of taking 4g longvida (640 mg curcumin), it would be about 6 g plus the oil. With turmeric in a meal would be good.
Filing a freedom-of-information act request through the government's website might obtain the exact formulation longvida is using, more data on this red blood cell surprise, and to get the full UCLA paper for free, not to mention all the emails between UCLA and verdue sciences (longvida).
Interesting quotes from the U.S. government (UCLA) patent that verdue science (longvida) uses:
patent:
http://www.google.co...1993365B1?cl=enwhere the curcuminoid is tetrahydrocurcumin, which is stable even at alkaline pH, the antioxidant may be dispensed with
Tetrahydrocurcumin is relatively stable in water at physiologic pH, is a competitive inhibitor of glucuronidation, and enhances absorption and, ultimately, plasma levels of curcumin.
To protect the curcuminoid against hydrolysis, a water-soluble antioxidant is employed. Nonlimiting examples include ascorbic acid (ascorbate, vitamin C and its acylated fat soluble derivatives), α-lipoic acid (alpha-lipoate), vitamin E and derivatives, N-acetylcysteine (NAC), and reduced glutathione (GSH). Even tetrahydrocurcumin provides curcumin some protection against hydrolysis. Mixtures of antioxidants also can be used,
Most previous efforts to explain curcumin's poor bioavailability have focused on rapid glucuronidation. However, tetrahydrocurcumin and curcumin are similarly hydrophobic and poorly soluble in water, and similarly rapidly glucuronidated and sulfated. Nevertheless, our data and data in the literature show that tetrahydrocurcumin is much more bioavailable than curcumin, with plasma levels from the same oral doses that are 7-8 times higher. The improved bioavailability of tetrahydrocurcumin is largely attributed to the fact that it is stable even at basic pH. In contrast, curcumin is unstable in aqueous solutions above pH 7.0 and therefore unstable in the intestinal tract where most absorption occurs. It hydrolyzes to ferulic acid and vanillin breakdown products. A preparation that stabilizes curcumin at slightly more basic pH is predicted to increase bioavailabilily of solubilized curcumin by as much as 7-8 fold. Combining curcumin with an additional water soluble antioxidant, for example ascorbate, can stabilize curcumin at pH 7.4.
We have tested serial dilutions of ascorbate and find stabilization is effective out to 4 hours (a typical absorption cycle), with curcumin:ascorbate ratios as high as 16: 1, with some small decline in efficacy between 8:1 and 16:1. Therefore, providing a curcuminoid-to-antioxidant ratio of about 10:1 or higher should be sufficient to prevent hydrolysis during absorption, and enhance bioavailability. As one nonlimiting example, a preparation containing 330 mg of curcumin (MW 368) would have only an additional 17.75 mg of ascorbate (MW 198). Thus, additional antioxidant need not add prohibitively to the bulk of a formulation.
Nonlimiting examples of glucuronidation inhibitors include tetrahydrocurcumin, piperine (Bioperine®), probencid (Probene®), and diclofenac.
Tetrahydrocurcumin, which gives 7- 8 times higher levels, is predicted to be much more available, more stable, and therefore, more effective than curcumin, and tetrahydrocurcumin is predicted to protect curcumin from glucuronidation. Further, our in vitro bioassay data show that, at 1:1 ratios, tetrahydrocurcumin and curcumin synergize together in vitro. Therefore, formulating tetrahydrocurcumin with curcumin with 1:1 or higher molar ratios of tetrahydrocurcumin to curcumin will improve bioavailability of curcumin and provide synergistic efficacy.
Glucuronidation and sulfation of curcuminoids can also be inhibited by esterifying a fatty acid or other acyl group to one or both hydroxyls in the two methoxyphenol groups that are the targets of rapid enzymatic glucuronidation and sulfation. The blocking ester groups will then be removed from the prodrug curcuminoid ester in vivo by esterases in the target tissues, releasing free curcumin. In principle, any fatty acid can be used for esterification.
The curcuminoid is solubilized using any of a number of water-solubilizing carriers. As used herein," water-solubilizing carrier" refers to an agent, composition, compound, or medium that provides a curcuminoid in a more water-soluble or water-dispersible form, or that interacts with the curcuminoid to impart greater water solubility or dispersibility. Broadly, two nonlimiting categories of carriers include lipid micelles and microencapsulated oils. (In another embodiment of the invention, the composition is provided as solid lipid nanoparticles (SLNs))
Lipids micelles containing a curcuminoid can be made with any of a variety of lipids. Nonlimiting examples include (i) fatty acids, e.g., stearic acid; (ii) phospholipids, for example, phosphoglycerides, e.g., phosphatidyl choline ("PC"), phosphatidylethanolamine, phosphatidylinositol; (iii) bile acids, e.g., deoxycholic acid (deoxycholate) and conjugates thereof (e.g., amino acid conjugates, such as glycocholate and taurocholate); (iv) edible oils, especially healthful oils, e.g., vegetable oils, olive oil, canola oil, fish oil;(iv triacylglycerols; (vi) mixtures of any of these and/or other lipids and derivatives, e.g., pharmaceutically acceptable salts, hydrates, and conjugates thereof. The combination of a phospholipid (e.g., PC or Soy lecithin or Egg lecithin) and another surfactant -- such as bile acid/salt (e.g., deoxycholate, taurocholate), Ethylene oxide/propylene oxide copolymers (Poloxamer 188, Polosamer 182, Poloxamer 407, Poloxamine 908), or Sorbitan ethylene oxide/propylene oxide copolymers (Polysorbate 20, Polysorbate a60, Polysorbate 80)) is particularly useful. Other useful lipids include natural lecithin, (a mixture of glycolipids, triglycerides, and phospholipids, including PC). In general, longer chain compounds are preferred over short chain compounds when the composition is provided as an emulsion.
Nonlimiting examples of suitable surfactants include: Phospholipids, e.g., soy lecithin, egg lecithin, phosphatidylcholine; ethylene oxide/propylene oxide copolymers, e.g., Poloxamer 188, Poloxamer 182, Poloxamer 407, Poloxamine 908; sorbitan ethylene oxide/propylene oxide copolymers, e.g., Polysorbate 20, Polysorbate 60, Polysorbate 80; alkylaryl polyether alcohol polymers, e.g., tyloxapol
Nonlimiting examples of suitable co-surfactants include: Sodium cholate, sodium glycocholate, sodium taurocholate, sodium taurodeoxycholate.
It is also possible to form lipid micelles in vivo by, e.g., dissolving a curcuminoid in an injestible oil, adding an antioxidant and glucuronidation inhibitor; microencapsulating the combined components, and allowing bile acids to form micelles in vivo.
Thus, one example of a practical formulation combining all 3 principles (solubilization with lipid, protection with antioxidant, and competitive inhibition and synergy with tetrahydrocurcumin), for humans would be 165 mg curcumin, 165 mg tetrahydrocurcumin, 17.7 mg of stabilizing antioxidant ( ascorbate, lipoate, NAC, GSH etc) and the rest DOC/PC micelles as above or as other amphiphilic lipids, for a 1 gm capsule.
Curcumin, docosahexaenoic acid, an antioxidant or antioxidant mix (vitamin C or lipodated vitamin C, alpha lipoic acid, vitamin E). Our data shows that when curcumin is dissolved in oil, plasma curcumin remains low, but red blood cell curcumin is quite high, which explains bioavailability despite negligible plasma levels. No other group has reported this fundamental observation that appears to be the simplest method of enhancing bioavailability. Other healthful oils can be used (fish oil, canola oil, other high omega-3 oil). In this formulation, curcumin in oil can be microencapsulated.
Inclusion of a solubilizing lipid greatly enhances the plasma and red blood cell levels of curcumin. In one experiment, 1:1 DHA:lecithin micelles were prepared, putting curcumin in hot DHA (55° C) and sonicating to disperse Curcumin delivered by PC-DHA micelles (but without an antioxidant or separate gluronidation inhibitor), and a curcumin concentration of 0.29 Mg/ml plasma and 0.96 in red blood cells was achieved (0.8 and 2.6 mm respectively). In contrast, using the Sabinsa formulation (with piperine, but no water-solubilizing carrier) yielded a curcumin concentration of 0.17 Mg/ml in plasma (0.46 mm). Long chain fatty acids, particularly unsaturated ones like DHA, have added value in routing lopohilic drugs to the lymphatics and reducing high first-pass losses.
