Clinical dermatology • Original article doi: 10.1111/j.1365-2230.2005.01908.

Topical application of 1-methylnicotinamide in the treatment

of rosacea: a pilot study
A. Wozniacka, M. Wieczorkowska,* J. Gebicki* and A. Sysa-Jedrzejowska
Department of Dermatology, Medical University of Lodz, Poland; and *Institute of Applied Radiation Chemistry, Technical University of Lodz, Poland

Summary Rosacea is a chronic facial dermatosis with a progressive course, which is characterized
by the presence of erythema, papules, pustules, telangiectasias and sebaceous gland
hyperplasia. However, the aetiology is still unknown; genetic predisposition,
gastrointestinal disorders (Helicobacter pylori), infestations with Demodex folliculorum
and environmental stimuli are considered to be involved in the inflammatory process.
A metabolite of nicotinamide, 1-methylnicotinamide (MNA+), has anti-inflammatory
properties, and this is the first study to test the effectiveness of this agent in treating
rosacea. In total, 34 patients with rosacea were treated with a gel containing 0.25%
MNA+ as a chloride salt, twice daily for 4 weeks, after which improvement was
observed in 26 ⁄ 34 cases. The improvement was good in 9 ⁄ 34 and moderate in
17 ⁄ 34, but no clinical effect was noted in seven subjects. In only one case was skin
irritation given as the reason for treatment withdrawal. These results indicate that
MNA+ might be a useful agent for treating rosacea.

tory processes. 1-methylnicotinamide (MNA+) is one of

Introduction
Rosacea is a common dermatological condition. Over
the years many possible aetiologies have been proposed,
including genetic predisposition, hypertension, Demodex
folliculorum (mite) infestation, and association with
internal diseases, especially gastrointestinal problems
connected with the presence of Helicobacter pylori
bacteria. None of these theories have been proven
beyond doubt. Diagnosis of rosacea is based on lability of
the vasculature. Vasomotor flushes occur under a
variety of circumstances: stress, temperature changes
(especially from cold to hot), and ingestion of alcohol or
hot food and drink.1
As the pathogenesis is not clearly defined, treatment
cannot act directly against the cause of the disease.
Treatment regimens usually interfere with inflamma-
Correspondence: Dr Anna Wozniacka, Department of Dermatology,
Medical University of Lodz, Krzemieniecka 5, 94-017 Lodz, Poland.
E-mail: wozniacka@bmp.net.pl
Conflict of interest: none declared.
Accepted for publication 4 May 2005
the two major primary metabolites of nicotinamide,
along with nicotinamide-N-oxide. MNA+ is further
metabolized to 1-methyl-2-pyridone-5-carboxamide
and 1-methyl-4-pyridone-5-carboxamide.2,3 Although
MNA+ exerts its therapeutic function through multiple
mechanisms, it seems that its anti-inflammatory prop-
erties are the prime mechanism. MNA+ can also be
considered as one of the nicotinamide adenine dinucleo-
tide (NAD+) analogues.4 The reduced form, nicotina-
mide adenine dinucleotide (NADH), has been shown to
be effective in the treatment of rosacea and contact
dermatitis.5
We decided to test the therapeutic potential of MNA+
in rosacea patients.
Patients and methods
The study was approved by the local ethics committee.
Patients diagnosed with erythematotelangiectatic or
papulopustular rosacea were recruited. The diagnosis
was made according to the criteria of the National
Rosacea Society Expert Committee.6 Before enrolment,
patients were not receiving treatment with any form of

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 1-Methylnicotinamide in the treatment of rosacea • A. Wozniacka et al.

topical or systemic medication, or the medications

were withdrawn at least 2 weeks before the study.
Concomitant skin infection on the area to be treated
was an exclusion criterion.
As MNA+ is a physiological, nontoxic substance4,7
and the patients were in generally good health, only
basic laboratory parameters were analysed before and
after the study (complete blood cell account, erythrocyte
sedimentation rate, glucose level, urinalysis).
A gel containing 0.25% MNA+ as a chloride salt
(Accos; Pharmena Ltd, Lodz, Poland) was topically
applied to the skin lesions twice daily.
The number of papules and pustules, erythema
intensity (0 ¼ none, 1 ¼ mild, 2 ¼ moderate, 3 ¼ Figure 1 Mean ± SD number of facial inflammatory papules and
severe) and patient evaluation of symptoms such as pustules during the treatment time. Statistical comparisons be-
skin burning or stinging (0 ¼ none, 1 ¼ mild, 2 ¼ tween weeks 0 and 1 (P < 0.001), weeks 0 and 2 (P < 0.001),
moderate, 3 ¼ severe) were evaluated on the baseline weeks 0 and 4 (P < 0.001), weeks 1 and 2 (P < 0.007), weeks
1 and 4 (P < 0.001), and weeks 2 and 4 (P < 0.02).
visit and after 1, 2, and 4 weeks during the study.
Improvement was recorded as good when more than
70% of papules or pustules flattened and there was
evidence of a decrease in erythema and patient symp-
toms, and moderate when 40–70% of inflammatory
lesions flattened and a reduction of erythema and
patient symptoms was recorded.

Statistical analysis

The range of measured variables, mean arithmetic

values and standard deviation were calculated, and the
Friedman and Wilcoxon tests were used to compare
mean values. Comparisons were considered significant
at P < 0.05.
Results
The study group consisted of 34 patients (32 women
and 2 men, aged between 29 and 45 years). Ten
patients were diagnosed as having erythema-
totelangiectatic rosacea and 24 subjects with the
papulopustular subtype. The disease duration ranged
from 4 weeks to 2 years.
Ten patients reported previous topical corticosteroid
use; the rebound effect after their discontinuation was
the reason for their inclusion after the washout period.
In 5 of the 10 patients, MNA+ gel was found to be
helpful. In seven other subjects, previous topical met-
ronidazole treatment was unsuccessful. Seventeen sub-
jects had not been previously treated.
Statistical analysis of the number of papules and
pustules, erythema and patients’ complaints (intensity
score) revealed significant differences between baseline
and weeks 1, 2 and 4 (P < 0.001 for all comparisons).
Figure 2 Mean ± SD erythema score (o) and intensity of patient
symptoms (x). For both variables the differences between weeks 0,
1, 2 and 4 were statistically significant (P < 0.001).
The first indications of clinical efficacy could be seen
after 1 week, but the longer the time period for
application of the gel, the better the results obtained
(Figs 1 and 2).
Good improvement was observed in three patients
with erythematotelangiectatic rosacea and six patients
with papulopustular subtype. Moderate improvement
was noticed in 5 volunteers with erythematotelangiect-
atic lesions and 12 with papulopustular. The patient
illustrated in Fig. 3 is a typical erythematotelangiectatic
case, which revealed moderate improvement. In seven
patients, no improvement was seen. Only one patient
complained of itching, burning and skin irritation,
which occurred after 2 days of topical gel application
and was the reason for treatment withdrawal (Table 1).

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1-Methylnicotinamide in the treatment of rosacea • A. Wozniacka et al.
Table 1 The clinical results of the study.
No. of patients with
Total no.
Clinical effect ER PR of patients
Good improvement 3 6 9
Moderate improvement 5 12 17
No clinical effect 2 5 7 proinflammatory cells and molecules to the surface of
Worsening 0 1 1 the vascular endothelium. The ability of MNA+ to
ER, erythematotelangiectatic rosacea; PR, papulopustular rosacea.
Laboratory examination did not reveal any abnormalit-
ies before or after the study. Ten patients continued this
form of treatment after the study, up to 7 months, as the
gel was well tolerated and maintained the improvement.
Discussion
Although the exact aetiology of rosacea is unknown, it
is considered to have an inflammatory and vascular
origin. Hypersensitivity to Demodex mites causes recruit-
ment of inflammatory and other immune cells into the
dermis and release of inflammatory mediators. Rela-
tionship between vascular and inflammatory events is
regarded as a result of the influence of inflammatory
mediators such as substance P, histamine, serotonin,
bradykinin or prostaglandins on vasodilatation.8,9
Marks10 also suggests that immune cells cause endot-
helial damage, which increases the capacity of facial
microvasculature and ultimately dilatation. Therefore
agents with anti-inflammatory properties are in the first
line of rosacea therapy.
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2005 Blackwell Publishing Ltd • Clinical and Experimental Dermatology, 30, 632–635
Figure 3 Rosacea patient before and after
the treatment.
Our previous investigations revealed that MNA+, a
metabolite of nicotinamide, possesses anti-inflammatory
properties and can be efficacious in acne vulgaris,
allergic contact dermatitis and burns.4,7 Its therapeutic
properties are thought to be associated with its ability to
release prostacyclin (PGI2) and to reduce adherence of
stimulate PGI2 production may have anti-inflammatory
effects. The ionic character of MNA+, which can bind to
glycosaminoglycans located on the surface of vascular
endothelium cells, is also thought to be associated with
its beneficial effects.4
The anti-inflammatory MNA+ properties were proved
by the decrease in the number of papules and pustules,
intensity of erythema, and patient symptoms. The first
clinical improvement could be seen in the first week, but
continuation of the treatment brought greater benefit
for patients. Although the study was designed as a
4-week trial, the good clinical effect resulted in some
patients continuing the gel application. Follow-up at
7 months in 10 subjects confirmed not only good
tolerance of prolonged gel application but also main-
tenance of improvement and control of recurrences.
Unfortunately we did not observe any influence on
telangiectasias.
In rosacea patients, topical treatment can sometimes
cause skin irritation. In our study, only one patient
developed this symptom, requiring withdrawal from the
study, so MNA+ gel seems to be well tolerated.
It is generally accepted that systemic and local
corticosteroids are contraindicated in rosacea patients.
Sometimes, in active form of disease, they are intro-
 1-Methylnicotinamide in the treatment of rosacea • A. Wozniacka et al.
duced to decrease inflammation by suppressing migra-
tion of polymorphonuclear leucocytes and reducing
capillary permeability.11 Potent steroid application
might be the cause of pan-facial papulopustular ery-
thema. This condition is extremely difficult to treat, as
the lesions are both steroid-induced and steroid-depend-
ent. Each attempt at steroid withdrawal worsens the
rosacea. Our preliminary observations indicate that
besides oral therapy such as tetracycline, metronidazole
or isotretinoin,12 which very often must be introduced,
local MNA+ gel applications could also be useful in those
cases.
Our study with this new agent of vitamin origin
shows promising results, which could justify further
investigation using a double blind, randomized study.
Acknowledgements
This work was supported by the grants from Medical
University (no. 503-119-1) and Ministry of Science and
Informatization (no. PBZ-KBN-101 ⁄ T09 ⁄ 2003).
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