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Niacin in therapy.Postepy
Hig Med Dosw (Online). 2007 May
15;61:288-302.
Niacin
(nicotinic acid and nicotinamide) is a vitamin used as a source of
the NAD+ and NADP+ coenzymes required for many metabolic
processes. Its low dietary levels induce the development of
pellagra. Niacin has been used for decades in the treatment of
patients with disturbed lipid and lipoprotein metabolism, this
being the main cause of atherosclerotic changes in cardiovascular
diseases. It is still the most efficacious drug in terms of its
ability to increase HDL cholesterol content accompanied by a
decrease in all atherogenic lipoproteins (VLDL, LDL, and L(a)) as
well as fatty acids and triglycerides. Niacin also increases
adiponectin level, which might result in additional
atheroprotection. There are studies confirming the beneficial
action of niacin against migraine and hyperphosphatemia associated
with renal failure, ethanol-induced neurodegeneration, and loss of
beta-cell function in type 1 diabetes. Moreover, it augments
plasma tryptophan concentrations in HIV-infected patients and
thyroid radiosensitivity to 131I. Inhibition of the invasion of
hepatoma cells has also been proven. However, it is necessary to
point out that the currently applied niacin preparations might
exhibit such side effects as cutaneous flushing, gastrointestinal
disturbances, and hepatotoxicity, particularly during treatment
with sustained-release niacin preparations. The recent discovery
of the G-protein-coupled receptor GPR109A, which mediates the
antilipolytic effects induced by nicotinic acid in adipocytes as
well as cutaneous vasodilation, allows the development of new
agents interacting with this receptor. In view of these
observations, niacin therapy must be accompanied by control of the
choice of niacin preparation and its dose in order to eliminate or
at least limit its side effects.
Niacin
nutritional status in HIV type 1-positive children: preliminary
data.J
Pediatr Gastroenterol Nutr. 2007
May;44(5):629-33.
OBJECTIVE:
HIV infection induces a state of pellagra in cell culture models.
This study compared the nutritional status and the 24-hour urine
excretion of N-methylnicotinamide between HIV-positive children
and HIV-negative children who were or were not born of mothers
with HIV-1 infection. PATIENTS AND METHODS: Forty patients were
included in the study: HIV-positive children (group 1; n = 20),
HIV-negative children born to infected mothers (group 2; n = 10),
and HIV-negative control children (group 3; n = 10). Usual dietary
intake was assessed by a semiquantitative food-frequency
questionnaire. Weight and height were assessed and compared with
the reference data of the U.S. National Center for Health
Statistics/Centers for Disease Control and Prevention. For the
estimation of fat-free mass and total body water, bioelectrical
impedance technique was used. N-methylnicotinamide was measured by
a modified method of high-performance liquid chromatography.
RESULTS: Groups were matched in relation to age, sex, percentage
of malnutrition, anthropometric measures, and body composition.
Daily niacin intake did not differ statistically across groups
(group 1 = 18.0 +/- 11.4 mg/day; group 2 = 18.9 +/- 8.0 mg/day;
group 3 = 14.2 +/- 5.2 mg/day), nor did intake of tryptophan,
vitamin B6, and zinc. The values of urinary niacin per gram of
creatinine were similar and adequate across the groups (group 1 =
4.68 [0.75-14.9]; group 2 = 3.74 [1.13-5.69]; group 3 = 3.85
[1.80-8.19]). CONCLUSIONS: HIV-positive children excreted the same
amount of N-methylnicotinamide in urine as did the control
children. These findings may be attributed to similarities in
nutritional status, adequate intestinal absorption (no children
experienced diarrhea) and stable clinical condition.
Pellagra.Sante.
2005 Jul-Sep;15(3):205-8.
Pellagra
is a systemic disturbance caused by a cellular deficiency of
niacin, resulting from inadequate dietary nicotinic acid and/or
its precursors, the essential amino-acid tryptophan. In Europe and
North America cases of pellagra are rarely encountered, but in
some developing countries this disease is frequent, and is the
most frequent clinical feature of nutritional deficiency of adult.
The principal causes of pellagra are: nutritional niacin
deficiency; chronic alcoholism; gastro-intestinal malabsorption;
some medications (5-fluoro-uracil, isoniazid, pyrazinamide
ehtionamide, 6-mercaptopurine, hydantoins, phenobarbital and
chloramphenicol). The diagnosis of pellagra is based on the
patient's history and the presence of "3 D syndrome": dermatitis,
diarrhea, and dementia. The dermatitis caused by pellagra is a
bilaterally symmetrical erythema at the sites of solar exposure.
The dermatitis begins in the form of an erythema with acute or
intermittent onset gradually changing to an exsudative eruption on
the dorsa of the hand, face, neck, and chest with pruritus and
burning. Acute dermatitis of pellagra resembles sunburn in the
first stages, sometimes with vesicles and bullae. The
gastro-intestinal disturbances are: anorexia, nausea, epigastric
discomfort and chronic or recurrent diarrhea. Anorexia and
malabsorbative diarrhea lead to a state of malnutrition and
cachexia. Stools are typically watery, but occasionally can be
bloody and mucoid. Neuropsychologic manifestation included
photophobia, asthenia, depression, hallucinations, confusions,
memory loss and psychosis. As pellagra advances, patient become
disoriented, confused and delirious; then stuporous and finally
die. Pathological changes in the skin is non-specific, there are
no chemical tests available to definitively diagnose pellagra.
However low levels of urinary excretion of N-methylnicotinamide
and pyridone indicates niacin deficiency. The treatment of
pellagra consisted to exogenous administration of niacin or
nicotinamide cures. Topical management of skin lesions with
emollients may reduce discomfort. The therapy should also include
other B vitamins, zinc and magnesium as well as a diet rich in
calories. The prevention is based in the nutritional education
(food sources of niacin: eggs, bran, peanuts, meat, poultry, fish,
red meat, legumes and seeds), and the eviction of alcohol.
Biochemical assessment of niacin deficiency among carcinoid cancer
patients.Am
J Gastroenterol. 2005
Oct;100(10):2307-14.
OBJECTIVE:
Carcinoid cancer patients often have elevated levels of serotonin
or its precursor 5-hydroxytryptophan. Normally, serotonin
synthesis accounts for a small fraction of tryptophan catabolism,
which should be directed along a pathway that allows partial
conversion to niacin; hence, increased diversion of tryptophan
toward serotonin could cause variable degrees of niacin deficiency
in carcinoid patients. Therefore, the prevalence of niacin
deficiency among carcinoid patients was investigated by clinical
assessment of pellagra and biochemical assessment of whole blood
niacin number, a ratio derived from two biologically active forms
of niacin (NAD/NADP x 100). METHODS: Clinical and biochemical
niacin status were assessed in a cohort of newly diagnosed
carcinoid patients with carcinoid syndrome (CCS, n = 36),
carcinoid patients without carcinoid syndrome (CWCS, n = 32) and
noncarcinoid controls (n = 24) recruited at two primary care
clinics. Other aspects of serotonin metabolism were measured by
analyses of plasma serotonin and tryptophan and urinary excretion
of 5-hydroxyindoleacetic acid. RESULTS: Biochemical niacin
deficiency (niacin number < 130) was significantly more common in
CCS patients (10 out of 36) compared to controls (p < 0.05,
Fisher's exact test), while CWCS patients displayed an incidence
that was not significantly elevated (4 out of 32). Only one CCS
patient, who was also identified biochemically as niacin
deficient, was clinically diagnosed with pellagra. CONCLUSION:
Biochemical niacin deficiency is more prevalent among newly
diagnosed CCS patients than in controls. Manifestation of pellagra
is a less sensitive indicator, and dependence on this endpoint
could lead to a lack of appropriate nutritional support for this
group of patients.
Niacin metabolite excretion in alcoholic
pellagra and AIDS patients with and without diarrhea.Nutrition.
2004 Sep;20(9):778-82.
OBJECTIVE:
Malnourished patients with the acquired immunodeficiency syndrome
(AIDS) can develop pellagra-like manifestations such as
dermatitis, diarrhea, and dementia; therefore, we tested the
hypothesis that patients with AIDS and diarrhea would have niacin
depletion. This study compared 24-h urine excretion of
N1-methyl-nicotinamide (N1MN) among patients with pellagra and
patients with AIDS who did and did not have diarrhea. METHODS:
Three groups were studied: G1 (patients with AIDS and diarrhea, n
= 5); G2 (patients with AIDS and no diarrhea, n = 7), and G3
(patients with alcoholic pellagra and without the human
immunodeficiency virus, n = 8). Diarrhea was defined as the
production of at least three liquid stools per day over 3 to 5 d.
Studies included mucosal intestinal biopsy, malabsorption tests,
detection of parasites in stool, and serum albumin measurements.
Semiquantitative food-frequency questionnaire, anthropometry, and
daily urinary N1MN excretion were also determined. Groups were
matched in relation to age, sex, presence of parasites in stool,
and intestinal absorption results. RESULTS: G1 had normal
intestinal examination by light microscopy and no parasites in
stools. G2 group showed lower levels of serum albumin (2.6 +/- 0.3
g/dL) when compared with G1 (3.4 +/- 0.3 g/dL) and G3 (3.1 +/- 0.7
g/dL). Except for patients with pellagra, groups met their energy
requirements. Patients in G3 (0.013, 0.01-0.081 mg/dL) and G1
(0.062, 0.001-0.33 mg/dL) excreted smaller amounts of N1MN in
urine than did those in G2 (0.63, 0.02-2.9 mg/dL). CONCLUSIONS:
Patients with AIDS and diarrhea excreted less N1MN in urine than
did those without diarrhea. These patients may have an impaired
niacin nutritional status, possibly associated with increased
metabolic needs.
Pellagra
encephalopathy following B-complex vitamin treatment without
niacin.Int
J Psychiatry Med. 2004;34(1):91-5
Pellagra is caused by nicotinic acid deficiency; it is rarely
encountered in developed countries, and it is mainly related to
poverty and malnutrition, as well as with chronic alcoholism. We
report the case of an alcoholic patient who was diagnosed with
pellagra and administered B-complex vitamin tablets that did not
contain niacin. A few weeks later, the patient developed
nervousness, irritability, insomnia and, consequently, delusional
ideas and hallucinations, for which he had to be hospitalized.
After his admission, the patient manifested loss of consciousness
and myoclonus. All of his symptoms (cutaneous, neurological, and
psychiatric) resolved fully with treatment with niacin in
combination with other B-complex vitamins. All undiagnosed
encephalopathies in alcoholic patients should be treated with
multiple vitamin therapy, including nicotinic acid.
Niacin,
poly(ADP-ribose) polymerase-1 and genomic stability.Mutat
Res. 2001 Apr 18; 475(1-2): 45-56.
Nicotinic
acid (NA) and nicotinamide (NAM), commonly called niacin, are the
dietary precursors for NAD(+) (nicotinamide adenine dinucleotide),
which is required for DNA synthesis, as well as for the activity
of the enzyme poly(ADP-ribose) polymerase-1 (PARP-1; EC 2.4.2.30)
for which NAD(+) is the sole substrate. The enzyme PARP-1 is
highly activated by DNA strand breaks during the cellular
genotoxic stress response, is involved in base excision repair,
plays a role in p53 expression and activation, and hence, is
thought to be important for genomic stability.In this review,
first the absorption, metabolism of niacin to NAD(+), as well as
the assessment of niacin status are discussed. Since NAD(+) is
important for PARP-1 activity, various aspects of PARP-1 in
relation to DNA synthesis and repair, and regulation of gene
expression are addressed. This is followed by a discussion on
interactions between dietary methyl donor deficiency, niacin
status, PARP-1 activity and genomic stability.In vitro studies
show that PARP-1 function is impaired and genomic stability
decreased when cells are either depleted from NAD(+) or incubated
with high concentrations of NAM which is a PARP-1 inhibitor. In
vitro as well as animal studies indicate that niacin deficiency
increases genomic instability especially in combination with
genotoxic and oxidative stress. Niacin deficiency may also
increase the risk for certain tumors. Preliminary data suggest
that niacin supplementation may protect against UV-induced tumors
of the skin in mice, but data on similar preventive effects in
humans are not available. NAM has been shown in vitro to have an
antioxidant activity comparable to that of ascorbic acid.Data on
niacin status and genomic stability in vivo in humans are limited
and yield ambiguous results. Therefore, no firm conclusions with
respect to optimal niacin intake are possible. As a consequence of
oral niacin supplementation, however, NAM levels in the body may
increase, which may result in inhibition of PARP-1 and increased
genomic instability. More studies are needed to define an optimal
level of niacin nutriture in relation to genomic stability and
tumorigenesis.
Niacin
as a potential AIDS preventive factor.Med
Hypotheses. 1999 Nov;53(5):375-9.
A pentad
of findings consistent with niacin depletion have been described
in patients with AIDS. There are also clinical and laboratory data
to support the potential benefit of niacin in HIV infection. In
this paper, it is hypothesized that HIV infection induces niacin
depletion, and that therapeutic niacin will act as an AIDS
preventive factor. While viral inhibition is incontrovertibly the
primary 'AIDS preventive factor', costly antiretroviral
medications are simply out of reach for the majority of the
world's HIV-infected people. Along with antiviral research,
investigation must go forward to look at strategies to overcome
the massive metabolic disruption caused by the production of
approximately one billion virus particles per day. Niacin, the
same B complex vitamin found in the early part of this century to
be the 'pellagra preventive factor', is proposed here as a
secondary 'AIDS preventive factor' in HIV-infected persons.
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ON THE IMAGE : Complications of Niacin Deficiency (Pellagra).