Topical Niacin Research Articles

Polymorphisms in PLA2G6 and PLA2G4C genes for calcium-independent phospholipase A2 do not contribute to attenuated niacin skin flush response in schizophrenia patients

We hypothesized that attenuated niacin skin flushing in schizophrenia patients might be associated with polymorphic variants in PLA2G6 and PLA2G4C genes (rs4375 and rs1549637 variations) which encode calcium-independent phospholipase A2 beta (iPLA2β) and cytosolic phospholipase A2 gamma (cPLA2γ) enzymes. The iPLA2β and cPLA2γ may play an important role in niacin-mediated signaling; in addition to their major role – mediating phospholipids remodeling, which alters membrane receptors and signal transduction, they regulate the reservoir of arachidonic acid for prostaglandins synthesis. Skin response to topical niacin of 0.1M, 0.01M, 0.001M and 0.0001M concentrations in 75 schizophrenia patients was rated using the method of volumetric niacin response (VNR). Neither PLA2G6 nor PLA2G4C gene polymorphisms were significantly associated with VNR values. Furthermore, polymorphisms׳ synergy on niacin skin flushing was also not detected.

The impact of PLA2G4A and PTGS2 gene polymorphisms, and red blood cell PUFAs deficit on niacin skin flush response in schizophrenia patients

We investigated the etiology of the attenuated niacin skin flush response in schizophrenia patients. Skin response to topical niacin of 0.1M, 0.01M, 0.001M, and 0.0001M concentrations was rated using method of volumetric niacin response (VNR) and correlated to two functional A/G polymorphisms in genes: phospholipase A2 group IVA (BanI of the PLA2G4A), and rs689466 of the prostaglandin synthase-2 (PTGS2). We further tested the possible correlation between niacin response and fatty acid (FA) content of red blood cells (RBCs). We detected statistically significant but weak impact of both polymorphisms on niacin flush response in schizophrenia patients. The dosage of the G alleles of both polymorphisms was associated with higher VNR values, although each polymorphic variant accounted for only 1% of the overall flush response variability. Regarding FA content, both n−3 and n−6 polyunsaturated FAs (PUFAs) were significantly reduced in the patient group, but an association with niacin sensitivity was not detected.

Enhancing effect of pretreatment with topical niacin in the treatment of rosacea-associated erythema by 585-nm pulsed dye laser in Koreans: a randomized, prospective, split-face trial

Enhancing effect of pretreatment with topical niacin in the treatment of rosacea-associated erythema by 585-nm pulsed dye laser in Koreans: a randomized, prospective, split-face trial

Topical niacin cream‐assisted 595‐nm pulsed‐dye laser treatment for facial flushing: retrospective analysis of 25 Korean patients

Flushing is defined clinically as a transient reddening of the face and other areas. Due to the transient nature of flushing, a patient may not show signs of flushing during laser treatment. The aim of this study was to evaluate the efficacy and safety of 595-nm pulsed-dye laser treatment of flushing or erythema after provocation of flushing by topical niacin cream. We retrospectively reviewed a total of 25 Korean patients with facial flushing who were treated with three sessions of 595-nm pulsed-dye laser after the application of topical niacin cream. Follow-up results revealed that 12 of the 25 patients demonstrated marked (51-75%) clinical improvement of baseline facial erythema. Eight patients had moderate (26-50%) improvement and three demonstrated near total (≥ 75%) improvement. Two patients showed minimal to no (0-25%) improvement. We observed that the reactivity to topical niacin cream was markedly reduced in 64% of our patients after 595-nm pulsed-dye laser treatments. Minimal post-therapy facial oedema was noted in most of the patients, which usually resolved spontaneously within 2 days. Pronounced facial swelling was observed in four patients. We suggest that 595-nm pulsed-dye laser treatment after provocation of flushing by topical niacin cream may provide a new treatment algorithm for facial flushing in Asians.

Enhancing effect of pretreatment with topical niacin in the treatment of rosacea-associated erythema by 585-nm pulsed dye laser in Koreans: a randomized, prospective, split-face trial

Rosacea is a chronic dermatosis that is usually confined to the face. A pulsed dye laser (PDL) system has been proven to be effective in treating rosacea-associated erythema and telangiectasias. Niacin is a cutaneous vasodilator that can increase the chromophore through increased blood flow. We hypothesized that increased blood flow by pretreatment with topical niacin could enhance the effect of PDL in the treatment of rosacea. Eighteen Korean patients with rosacea were recruited. Three sessions of 585-nm PDL using a subpurpuragenic dose with and without pretreatment with niacin cream were performed on randomly assigned half-faces at 3-week intervals. Erythema was assessed objectively by a polarization colour imaging system, and evaluations were also made by three blinded dermatologists. Patient satisfaction was evaluated using a 10-point visual analogue scale. Fifteen patients completed this study. All patients showed an improvement in erythema after three sessions of PDL treatment both with and without niacin pretreatment (P = 0·023 and P = 0·009, respectively). There was no significant difference in the improvement of objective erythema between the two sides. However, based on physician assessment the overall clinical improvement on the niacin side was significantly higher (P = 0·005), and patient satisfaction was also higher on the niacin-pretreated side (P = 0·007). There were no remarkable side-effects, with the exception of transient erythema and oedema. Pretreatment with topical niacin safely enhanced the effect of 585-nm PDL treatment of rosacea-associated erythema in Koreans. Application of niacin can be helpful in overcoming the relatively lower effect of subpurpuragenic PDL in dark-skinned Asians.

Persistent erythema with niacin is not attributable to aspirin resistance

Niacin is suboptimally used in patients because it causes flushing and erythema. These side effects have been attributed to release of the vasodilating prostaglandin D2, generated in a reaction catalyzed by cyclooxygenase-1. Aspirin reduces but does not completely eliminate these side effects. Because some patients are resistant to its antiplatelet effects, we hypothesized that patients with persistent niacin-induced erythema might be aspirin resistant. Platelet function studies (via the use of a whole-blood platelet function aggregometer [VerifyNow; Accumetrics, San Diego, CA] with end points of aspirin reaction unit [ARUs] and P2Y12 reaction units [PRUs]) were performed on 32 healthy, drug-free subjects before and after 324 mg of aspirin. A niacin skin test with the use of topical methylnicotinate was also performed before and after the administration of aspirin. Responses to methyl nicotinate were assessed by a reaction score and by counting the time to first visible redness (TTR). All subjects had an expected decrease in arachidonic acid induced platelet response (ARU 642.8 ± 47.20 before to 431.5 ± 41.1 after aspirin, P < .0001) without a significant change in the PRU. The reaction score and TTR were prolonged by aspirin at methylnicotinate concentrations ≥ 0.001 M. Although no subject had aspirin resistance (defined as ARU > 550), there was considerable variability in skin responses with erythema elicited in all subjects at the greatest concentrations. There was no difference in the ARU for subjects with TTR values above and below the mean, indicating that aspirin resistance does not explain the variation in skin responses to a topical niacin derivative. Aspirin resistance is unlikely to be a significant contributor to the persistent erythema and flushing in niacin-treated patients.

The topical niacin sensitivity test: An inter- and intra-rater reliability study in healthy controls

Topical application of nicotinic acid results in erythema, and in some cases oedema of the skin, supporting a strong relationship between niacin sensitivity and prostaglandin D2. The aim of this study was to examine the inter-rater and intra-rater reliability of a 12-min niacin sensitivity test in healthy adults. Three raters assessed the skin reaction of 12 volunteers, over 3-min intervals across four niacin concentrations (0.1, 0.01, 0.001, and 0.0001), and over six sessions. Inter-rater reliability estimates ranged from 0.85 to 0.97 for the total niacin sensitivity score. Similar inter-rater reliability estimates were found for niacin sensitivity ratings by concentration and time. Intra-rater reliability estimates ranged from 0.63 to 0.93 for the total niacin sensitivity score. These data indicate that the 12-min topical niacin sensitivity test has excellent reliability.

Impaired Flush Response to Niacin Skin Patch Among Schizophrenia Patients and Their Nonpsychotic Relatives: The Effect of Genetic Loading

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia.

Potential use of the topical niacin skin test in early psychosis—a combined approach using optical reflection spectroscopy and a descriptive rating scale

The niacin skin phenomenon reflects a prostaglandin (PG) mediated flush and oedema reaction. As PG metabolism is linked to breakdown of membrane lipids, diminished sensitivity to niacin application suggests potential disturbance in membrane phospholipid—arachidonic acid—PG pathways. We aimed to evaluate and quantify topical niacin skin reaction in early psychosis using optical reflection spectroscopy (ORS) and a new descriptive assessment scale integrating time course, redness, and oedema. Niacin skin tests were performed on 25 medicated first-episode psychosis patients fulfilling DSM-IV criteria for schizophreniform psychosis or schizophrenia and on 25 healthy controls. Nicotinic acid was applied in four dilution steps to the subjects inner forearm skin and skin reaction was consecutively assessed using ORS and a seven point rating scale. Both descriptive ratings and spectroscopic measures revealed significant group differences at the lower niacin concentrations (0.001 and 0.0001 M). At higher concentrations (0.01 and 0.1 M) only descriptive ratings were capable to show significant group effects. Data of both methods showed moderate to strong correlation ( r=0.605) as long as the erythema was not affected by the oedema. The data suggest that niacin sensitivity is inversely correlated with negative symptoms. Both methods demonstrate that niacin sensitivity is impaired in a group of first episode psychosis patients and are therefore able to distinguish a subgroup of patients with metabolic impairment. Niacin sensitivity in high risk populations and the specificity of impaired skin response are subjects of further investigation.