Curcumin and FIV
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Curcuminoids are the primary content of the culinary spice turmeric. There is no research
relating directly to curcumin as an FIV therapy, but there is an abundance of research with regard
to HIV. The total picture presented by this research is checkered. Curcumin may or may not be
an indicated supplement for someone with HIV, although the balance of evidence is toward the positive. On the one hand, in vitro experiments have
established that curcumin inhibits protease and integrase, two enzymes required for viral
replication [Mazumder]. It can also inhibit replication of HIV by inhibiting transcription
signalling of the viral long terminal repeat, the end-gene that functions as an on-off switch [Li]. Curcumin binds and activates a receptor (PPAR-γ) on dendritic cells which inhibits their ability to capture HIV and unwittingly transfer infection to T-cells [Jacob]. Curcumin also down-regulates AP-1 transcription factor, which is known to be one of the major host factors coopted by FIV to boost viral replication [Ishikawa]. And curcumin down-regulates human CXCR4 [Skommer], which is nearly (94.9%) identical to feline CXCR4 and which is the primary co-receptor on the cell surface used (along with the CD134 molecule to which the virus initially binds) to infect cells. Curcumin has strong anti-inflammatory qualities through suppression of inflammatory signaling proteins (“cytokines”) TNF-α, Interleuken (IL)-1β, and IL-6; however it also inhibits synthesis of IL-2 (necessary to activation and expansion of CD4+ T cells), suppresses IL-12 ( a co-stimulatory molecule, along with IL-2, necessary to CD8+ cell activation), and upregulates IL-4
and IL-10, both inducing antibody, not T cell immune response [Kang]. Although other
suppressors of IL-2 and IL-12 have shown therapeutic value through in vivo studies, no in vivo studies have clearly established curcumin’s desirability for antiretroviral therapy. Questions, therefore, linger regarding its possible benefit, although the preponderance of evidence points in that direction.
In 1994, Search Alliance, a Los Angeles community based research group, reported the results of
their 20-week pilot study in which curcumin (2.6 grams per day) “was able to produce a mild
antiviral effect in terms of reduction of viral load as measured by RNA PCR in all 11 of the 19
participants who completed the study. . . although no increase in CD4 cells were reported”
[Hale]. Several years later, a New England clinical trial involving HIV patients “examined
curcumin and its effectiveness as an antiviral agent in 40 participants. Viral load tests, including
baseline testing, were conducted in the fourth and eighth weeks, following high- and low-dose
regimens. The study found no evidence that curcumin reduced viral load or increased CD4
counts. Despite this finding, patients claimed they liked taking curcumin because they felt better
and were willing to put up with the minor gastrointestinal effects” [James]. This result should
not be surprising, however, because curcumin suffers from a defect that adversely impacts almost
every therapeutic use in which systemic rather than local action is required: it has poor bioavailability, and what is bioavailable is metabolized and excreted quickly. This is not a problem in treatment of diseases such as gingivostomatitis or bowel diseases, where curcumin comes in direct contact with inflamed or infected tissue. Systemic
problems are another matter entirely.
The unresolved issue of curcumin’s suitability as antiretroviral therapy is made all the more vexing
by the fact that human and animal studies have established curcumin’s usefulness in treating
inflammatory diseases, many of which are secondary complications of FIV. These include
pancreatitis [Durgaprasad], colitis & inflammatory bowel disease [Holt], retroviral associated
diarrhea [Conteas], hepatitis, jaundice, diabetes, and bacterial infections [Itokawa]. Anecdotal success in treating feline gingivostomatitis has also been reported. This anti-inflammatory activity is accomplished through curcumin’s ability to affect “the metabolism of arachidonic acid, activities of cyclooxygenase, lipoxygenase, cytokines (interleukins and tumor necrosis
factor), nuclear factor-kB (NF-κB) and release of steroids” [Itokawa]. There is also an
accumulating mountain of data on curcumin’s promise in treating a variety of cancers, including
lymphoma, the most frequent fatal feline cancer. “Curcumin has been shown to have cancer
chemopreventive potential against a variety of tumors via targeting key survival pathways that
are aberrantly activated in cancer cells. . . . curcumin hardwires to multiple cellular processes.
Suppression of cell proliferation, induction of apoptosis, and inhibition of metastasis are
considered to be the major mechanisms underlying its anticancer properties” [Uddin].
For improved systemic benefit, formulation of curcumin with substances designed to boost systemic uptake is highly desirable. This has been accomplished in several ways.
One is the combining of curcumin with the piper nigrum extract piperine, marketed as Bioperine. In one study in humans “after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects” [Shoba]. Several brands of curcumin supplements are commercially available in which the curcumin is mixed with piperine.
An alternative route to boosting bioavailability (and antioxidant capacity) is through lipidation of the curcumin by several trade-marked processes described individually as “patent pending.” Increases in peak serum concentration and sustained retention time tend to vary from study to study, but each process registers significant increases in both areas and exceeds piperine-boosting in the latter. One process, marketed as Meriva™, uses curcumin-phosphatidylcholine complexes and has been validated by several trials [Maiti][Marczylo]. (One manufacturer offers a time-release formulation of Meriva.) Longvida is another recent entrant to the field demonstrating enhanced bioavailability [Gota]. Its formulation is described as a “solid lipid curcumin particle (SLCP)” complex. A third approach, trademarked as Biocurcumax (BCM 95™), involves blending standardized curcuminoids with an essential oil of turmeric [Benny]. Curcu-Gel uses a trademarked “softsule®” delivery of BCM 95 and cites a trial showing improved bioavailability [Mukkadan]. Thorne has recently introduced a lipid formulation intended for animals called CurcuVet. Citation of research by Thorne seems to indicate that the product is based on the Meriva formulation. For those using products intended for humans, powders may prove easier to downsize to a desired feline dosage.
Perhaps the most promising and exciting development has been the expanding research into encapsulation of curcumin in tiny nanoparticles as vehicles for uptake and intracellular transport. Studies have demonstrated that the unique size range and solubilizing properties of such nanoparticles increase bioavailability and enhance activity against a variety of bacterial and fungal pathogens [Wang]. A recent HIV study used apotransferrin, a glycoprotein related to lactoferrin, to carry curcumin into HIV-infected cell lines via the cells' transferrin receptors. Researchers found that curcumin so delivered had magnified anti-inflammatory action and inhibited HIV at the integration (into cellular DNA) stage in a way that the same curcumin not encased in nanoparticles did not [Gandapu]. Life Enhancement has marketed a nanocurcuminoids product in which curcuminoids are encased in solid lipid nanospheres, or SLNs. The curcuminoids are dissolved into a lipid during the process of encasement in a phospholipid shell [Wang].
Curcumin is a safe supplement for cats. Toxic limits have been set very high in animal studies,
and although ulcerogenic dosages in a study of rats were set at 100 mg/kg [Prasad], one private pet owner, whose cat suffered from myelofibrosis, has reported via his website daily dosages as high as 1 to 1 1/2 gms of unenhanced curcumin and 500 mgs of both piperine-enhanced curcumin and Curcu-Gel without side effects. While there is no information to suggest what an FIV-specific dosage might be, one veterinary source has suggested c.70 mg twice daily for control of stomatitis [Rochette]. Liposomal formulations necessarily contain less curcumin per unit volume to accommodate the lipid carrier, so more mg/kg are possible, although practical limitations relating to administering to a cat must be taken into account. Because it induces bile flow, curcumin should not be given to cats with impaired bile duct clearance. Reports are that curcumin/turmeric is mild enough in taste that some cats willingly eat food to which it has been added. It does stain, however, so administration to vomiting cats may cause problems for the owner.
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