Niacinamide and FIV
Niacinamide [alternatively called nicotinamide] is one of the two forms of the B3 vitamin
Niacin. The other form is nicotinic acid. Each form tends to have different therapeutic uses.
Nicotinic acid has no significant activity against HIV; niacinamide has been called by one
blogger "the perfect anti-HIV compound" [1]. Unfortunately, as is so often the case, there is no
discoverable research on niacinamide as an FIV therapy. However, at least some of its varying
modes of action against HIV suggest that it probably has value as an FIV therapy, too. One HIV
study found that at three to four times RDA dosage in humans progression to AIDS was delayed
and survival rates improved[2].
Niacinamide has properties which are antiviral, anti-apoptotic, and myeloproliferative
The antiviral properties are linked to the ability of niacinamide to inhibit an enzyme called
PARP-1, or poly ADP-ribose polymerase-1. PARP-1 is recruited to DNA which has been
damaged by oxidative stress. HIV preferentially seeks out damaged DNA to integrate itself into
the host genes. This is one of a number of reasons why oxidative stress furthers the advancement
of HIV infection. When the HIV DNA has been inserted in the host gene through the operation of
its own enzyme, integrase, the newly synthesized chain lacks several necessary base pairs of
nucleic acids at the junctions of viral and host DNA. The function of PARP-1 is to complete the
formation of the necessary base pairs. If PARP-1 is inhibited, the infection of new cells is
blocked [3]. (PARP-1 inhibition also gives nicotinamide antiviral action at the post-integration
stage via another route [4].)
Oxidative stress also figures into niacinamide's ability to inhibit virally-induced loss of Helper-T (CD4+) cells in several
ways. Normal and HIV-driven oxidative stress, through stimulation ("upregulation") of the
proinflammatory cytokine TNF-alpha, encourages a form of cellular suicide called "apoptosis,"
which is more responsible for the loss of healthy immune cells than actual viral infection.
Viral Alteration of the functioning of mitochondria, the energy-producers of immune cells, can induce
apoptosis. Along with other antioxidants, such as NAC (n-acetylcysteine) and carnitine (L-carnitine and its metabolite acetyl-l-carnitine), niacinamide exerts a protective effect on mitochondria, in part by
downregulating proinflammatory cytokines [5]. DNA strand breaks associated with oxidative
stress also lead to cellular apoptosis. "The addition of nicotinamide . . . significantly reduced
DNA fragmentation of both in vitro HIV-1-infected MT-4 cells and lymphocytes," suggesting "
that nicotinamide may be involved in the modulation of HIV-1-related apoptosis"[6].
Neutropenia (dearth of neutrophils) is a not uncommon consequence of FIV and HIV infection
because of viral suppression of host factors necessary to myeloproliferation. G-CSF (granulocyte
colony stimulating factor), a useful medication in humans for stimulating neutrophil production,
unfortunately has very limited usefulness in cats because of an antibody response to the human-cell origin of the drug. However, a recent study “identified nicotinamide
phosphoribosyltransferase (NAMPT), also known as pre-B cell colony enhancing factor (PBEF),
as an essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered
granulopoiesis in healthy individuals and in individuals with severe congenital neutropenia. . . .
Treatment of healthy individuals with high doses of vitamin B3 (nicotinamide) . . . induced
neutrophilic granulocyte differentiation. The molecular events triggered by NAMPT include . . .
upregulation of G-CSF synthesis and G-CSF receptor expression. G-CSF, in turn, further
increases NAMPT levels. These results reveal a decisive role of the NAD+ metabolic pathway in
G-CSF-triggered myelopoiesis” [13].
Niacin is one of a number of necessary nutrients that are found to be in short intracellular supply
in people infected with HIV. HIV-1 infection of human cells in vitro has been found to lead to
significant decreases in the intracellular concentration of NAD (Nicotinamide adenine
dinucleotide). There is a disease called pellagra which is caused by an insufficiency of the NAD
parent, niacin. This is what one HIV study has to say: "We conclude that HIV induces a state of
intracellular pellagra which is reversed by the administration of nicotinamide. . . . our data could
provide the rationale for the use of such agents in addition to antiviral drugs in primary
infection"[7]. The same authors, in a different study, extended the remedial effects of
niacinamide to deficiencies of tryptophan, which have been found to occur in direct proportion to
the rise in viral load and which have been linked to the onset of AIDS symptoms [8] “Decreased
plasma tryptophan in persons infected with human immunodeficiency virus (HIV) was first
reported over a decade ago, and this observation has since been confirmed by many groups. . . .
Starting with the hypothesis that HIV induces a pellagra-like state and that plasma tryptophan in
HIV-infected patients is decreased as a known biochemical correlate of pellagra, we predicted
that niacin therapy would reverse plasma tryptophan depletion as it does in pellagra. . . . After
receiving approval from the institutional review board, we treated HIV-infected patients for 2 mo
with high-dose niacin in the form of oral nicotinamide. . . . There was an average 40% increase in
plasma tryptophan (P = 0.01) in the four HIV-infected individuals who completed the 2-mo
protocol. . . . There were no adverse side effects attributable to this treatment. . . . This report
marks the first successful use of a vitamin to reverse this HIV-induced metabolic abnormality”
[9].
A recent FIV study arrived at a very similar conclusion. “Serum tryptophan concentration was
significantly lower and serum kynurenine concentration was significantly higher in FIV-positive
cats. The kynurenine: tryptophan ratio was >3-fold higher in FIV-positive animals, indicating
increased tryptophan catabolism in this group. Dietary or pharmacologic intervention to support
serum tryptophan concentrations has been shown to be clinically useful in humans with AIDS
and might be applicable to cats with FIV infection”[14]. There is every likelihood that
niacinamide supplementation would have the same effect on levels of serum tryptophan in cats as
in humans.
The RDA for niacin and niacin components is probably modest in cats. For humans it is set at
only 20mg daily. However, the toxic threshhold in cats has been set, roughly, at >350mg/kg of
body weight [10]. In diabetic children dosage is 150-300mg per year of age [11]. Dogs of <10lbs
are prescribed 250mg three times daily for treatment of discoid lupus erythematosus [12]. Feline
pelagra has been treated with 80-100mg daily [10]. With veterinary recommendation, dosages of
100mg 3 times daily have been reported.
____________________________________________________________
References
[1] http://www.grouppekurosawa.com/hivprotocolprint.htm
[2] Tang AM, Graham NM, Saah AJ. Effects of micronutrient intake on survival in human
immunodeficiency virus type 1 infection. Am J Epidemiol. 1996 Jun 15;143(12):1244-56.
http://www.grouppekurosawa.com/hivprotocolprint.htm
[3] Ha HC, Juluri K, Zhou Y, Leung S, Hermankova M, and Snyder SH. Poly(ADP-ribose)
polymerase-1 is required for efficient HIV-1 integration. Proc Natl Acad Sci U S A. 2001 March
13; 98(6): 3364–3368. http://www.pubmedcentral.nih.gov/pubmed/11248084?
[4] Michael F. Murray. Nicotinamide: An Oral Antimicrobial Agent with Activity against Both
Mycobacterium tuberculosis and Human Immunodeficiency Virus. Clinical Infectious Diseases
2003;36:453–460. http://www.journals.uchicago.edu/doi/abs/10.1086/367544
[5] Cossarizza A, Mussini C, Mongiardo N, Borghi V, Sabbatini A, De Rienzo B, Franceschi C.
Mitochondria alterations and dramatic tendency to undergo apoptosis in peripheral blood
lymphocytes during acute HIV syndrome. AIDS. 1997 Jan;11(1):19-26.
http://www.ncbi.nlm.nih.gov/pubmed/9110071?
[6] Savarino A, Martini C, Orofino GC, Cantamessa C, Castelli L, Pich PG, Sinicco A, Pugliese A. Apoptotic DNA fragmentation, and its in vitro prevention by nicotinamide, in lymphocytes
from HIV-1-seropositive patients and in HIV-1-infected MT-4 cells. Cell Biochem Funct. 1997
Sep;15(3):171-9. http://www.ncbi.nlm.nih.gov/pubmed/9377795?
[7] Murray MF, Nghiem M, Srinivasan A. HIV infection decreases intracellular nicotinamide
adenine dinucleotide [NAD]. Biochem Biophys Res Commun. 1995 Jul 6;212(1):126-31.
http://www.ncbi.nlm.nih.gov/pubmed/7611995?
[8] Zangerle R, Widner B, Quirchmair G, Neurauter G, Sarcletti M, Fuchs D. Effective
antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection. Clin
Immunol. 2002 Sep;104(3):242-7.
http://www.ncbi.nlm.nih.gov/pubmed/12217334?
[9] Murray MF, Langan M, MacGregor RR. Increased plasma tryptophan in HIV-infected
patients treated with pharmacologic doses of nicotinamide. Nutrition. 2001
Jul-Aug;17(7-8):654-6.
http://www.ncbi.nlm.nih.gov/pubmed/11448590?
[10] http://darwin.nap.edu/books/0309036828/html/26.html
[11] http://www.thorne.com/pdf/journal/7-6/niacinamide_mono7-6.pdf.
[12] http://www.vetinfo.com/dlupus.html
[13] Skokowa J. NAMPT is essential for the G-CSF–induced myeloid differentiation via a
NAD+–sirtuin-1–dependent pathway. Nature Medicine 15, 151 - 158 (2009).
http://www.nature.com/nm/journal/v15/n2/abs/nm.1913.html?lang=en
[14] Kenny MJ, Baxter KJ, Avery NC, Addie D, Gruffydd-Jones T, Tasker S. Altered
tryptophan metabolism in FIV-positive cats. J Vet Intern Med. 2007 May-Jun;21(3):539-41. http://www.ncbi.nlm.nih.gov/pubmed/17552465?
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