CVD is the primary contributor to global mortality and is expected to continue as the leading cause of death worldwide, with an estimated 23 million fatalities by 2030 from a value of 18·6 million in 2019(Reference Cd1,Reference Roth, Mensah and Johnson2) . The likelihood of developing CVD is associated with unhealthy eating habits alongside lack of physical activity, being overweight or obese, experiencing stress, alcohol consumption and smoking(Reference Anand, Hawkes and De Souza3,Reference Artinian, Fletcher and Mozaffarian4) . Dyslipidaemia is considered a significant factor influencing atherosclerosis process,(Reference Mendis, Puska and Norrving5) which is a major determinant of CVD. LDL is the primary apo B-containing lipoprotein present in human plasma. An elevated level of LDL-cholesterol, known as hypercholesterolemia, is the most common form of dyslipidaemia and is associated with an increased risk of CVD(Reference Arca, Pigna and Favoccia6). While LDL contains varying amounts of cholesterol, each lipoprotein has only one apo B protein. Consequently, apo B serves as a more reliable predictor of the number of LDL particles compared with LDL-cholesterol, which can predict cardiovascular events, including myocardial infarction(Reference Carr, Hooper and Sullivan7,Reference Walldius, Jungner and Holme8) . On the other hand, apo A1 functions as a major structural protein of high-density lipoprotein. Its key role involves facilitating cholesterol transport by removing excess cholesterol from peripheral tissues and delivering it to the liver and maintaining cellular cholesterol homeostasis. Therefore, there is a negative correlation between apo AI concentrations and the risk of CVD(Reference Karthikeyan, Teo and Islam9,Reference Walldius and Jungner10) .
Dyslipidaemia may be treated with the help of nutritional supplements including vitamins and other nutraceutical compounds(Reference Cicero, Colletti and Bajraktari11–Reference Shidfar, Keshavarz and Hosseyni14). Two meta-analysis studies have evaluated the impacts of vitamins on apo B and A1. Both studies found that pooling the results of seven randomised controlled trials (RCT) investigating the effects of vitamin D or vitamin E supplementation on apo A1 and apo B100 levels yielded nonsignificant effects(Reference Hamedi-Kalajahi, Zarezadeh and Dehghani15,Reference Radkhah, Shabbidar and Zarezadeh16) . However, niacin or nicotinic acid is a widely recognised treatment for lipid disorders, with efficacy in reducing plasma TAG, increasing HDL-cholesterol levels, reducing cardiovascular mortality rates and improving vascular function(Reference Florentin, N Liberopoulos and Kei17,Reference Hamilton, Chew and Davis18) . It is capable of reducing LDL particle numbers while increasing the size of LDL from small type B to large type A. Moreover, niacin enhances apo B degradation and lowers the fractional catabolic rate of HDL-apo A1(Reference Ruparelia, Digby and Choudhury19,Reference Al-Mohaissen, Pun and Frohlich20) .
Various vitamin B3 formulations are designed to control the gradual release of niacin. Immediate-release niacin causes quick flushing, while intermediate-release niacin lessens flushing intensity. Moderate-release niacin enhances tolerability by controlled release. Extended-release niacin (ERN) minimises flushing over an extended period(Reference Superko, McGovern and Raul21). Several clinical trials are being conducted to assess the effects of different types of niacin, administered at varying dosages, on apo A1 and B. In an RCT conducted by Scoffone et al. on Thalassemic patients, it was demonstrated that a 12-week treatment with ERN resulted in an increase in HDL-cholesterol compared with the placebo treatment. Although there was no significant difference in the mean change of apo AI between the study groups, the researchers reported a significant reduction in the ratio of LDL-cholesterol to HDL-cholesterol and apo B to apo A1 in the niacin-treated group when compared with patients who received the placebo(Reference Scoffone, Krajewski and Zorca22). An investigation focusing on diabetic patients with renal ischaemia demonstrated that the combination of atorvastatin and ERN treatment significantly raised HDL-cholesterol and apo A1 levels compared with patients who only received atorvastatin. However, this combination treatment did not have a significant reducing effect on LDL-cholesterol levels(Reference Yasmeen, Dawani and Mahboob23). Superko et al. conducted an RCT on hypercholesterolemic patients to investigate the impacts of two forms of nicotinic acid: immediate-release niacin and ERN on apo. The study revealed that both forms of nicotinic acid significantly increased apo A1 levels, while also significantly reducing apo B levels compared with patients who received the placebo(Reference Superko, McGovern and Raul24). Findings from a meta-analysis study demonstrated that niacin could have positive effects on the levels of LDL-cholesterol and HDL-cholesterol in individuals with type 2 diabetes(Reference Ding, Li and Wen25). Nonetheless, there has been a lack of meta-analysis investigating the extent of effectiveness of niacin treatment on apo A1 and B. In this study, we conducted a systematic review and meta-analysis of published clinical trials that utilised any form of this vitamin as an intervention, with blood levels of apo B and apo A1 as the measured outcomes.
Methods
This systematic review and meta-analysis adhered to the guidelines outlined in the PRISMA statement(Reference Page, Moher and Bossuyt26), ensuring comprehensive and transparent reporting of the study. The registration of this review was completed in PROSPERO under the reference number CRD42023444659.
Search strategy
A comprehensive search of the literature was performed across various online databases of PubMed, Scopus, Web of Science, Embase and Cochrane library, from inception up to July 2023. The search strategy incorporated the following keywords: (Niacin OR ‘nicotinic acid’ OR ‘acipimox’ OR niaspan) AND (‘Apolipoprotein A1’ OR ‘ApoA1’ OR ‘Apo A1’ OR ‘Apolipoprotein B’ OR ‘ApoB’ OR ‘Apo B’) AND (Intervention OR ‘Intervention Study’ OR ‘Intervention Studies’ OR ‘controlled trial’ OR randomized OR random OR randomly OR placebo OR assignment OR ‘clinical trial’ OR Trial OR assignment OR ‘randomized controlled trial’ OR ‘randomized clinical trial’ OR RCT OR blinded OR ‘double blind’ OR ‘double blinded’ OR trial OR ‘clinical trial’ OR trials OR ‘Pragmatic Clinical Trial’ OR ‘Cross-Over Studies’ OR ‘Cross-Over’ OR ‘Cross-Over Study’ OR parallel OR ‘parallel study’ OR ‘parallel trial’) (online Supplementary Table 1). There were no limitations regarding language or time in the search process. To facilitate the screening process, all identified studies were imported into the EndNote software. After removing duplicate citations, the remaining studies from the initial search underwent screening based on their titles and abstracts. Subsequently, eligible studies were subjected to a thorough full-text review. Furthermore, to ensure inclusiveness, the reference lists of relevant studies were manually examined. The literature search and screening process were conducted by two separate investigators (EYR & SS) working independently.
Inclusion and exclusion criteria
The study selection process followed specific criteria, focusing on RCT that involved adult participants aged 18 years or older. These trials investigated the impact of various forms of niacin administration on serum apo B and apo A1 levels. To be included, the RCT had to provide mean and sd at both the beginning and the end of the intervention for both the treatment and control groups. The selection process adhered to the PICO framework(Reference Higgins and Green27), encompassing the following elements: Participants (adults ≥ 18 years), intervention (niacin), comparison (placebo or no intervention group) and outcomes (serum levels of apo B and apo A1).
Exclusions were made for in vitro studies, experimental and ecological studies, observational papers and review articles. Additionally, trials without a placebo or control group were also excluded from the study. Furthermore, studies with a two-arm intervention duration or dosage were treated as two separate entities during the selection process.
Data extraction
Data extraction was conducted by two independent investigators (ES & SS). Any discrepancies or disagreements were resolved through discussion to reach a consensus. The relevant information from each study was carefully extracted into an Excel sheet. This included details such as the first author’s name, publication year, participants’ gender and mean age, study design, country of origin, sample sizes for both control and intervention groups, niacin dosage, type of niacin, type of control intervention, duration of the intervention, health status and disease conditions of the studied population, mean changes and sd of apo B and apo A1 throughout the trials for both the intervention and control groups. When numerical estimates were presented in graphical format, we used the plot digitiser tool (http://plotdigitizer.sourceforge.net/) to extract the data accurately.
Quality assessment
The Cochrane quality assessment tool was employed to evaluate the potential bias risk in each study included in the current meta-analysis(Reference Higgins, Altman and Gøtzsche28). This tool comprises seven domains, which involve aspects like random sequence generation, allocation concealment and various sources of bias (reporting, performance, detection, attrition, etc.). For each domain, a ‘high risk’ score was assigned if the study contained methodological errors that might have influenced its findings. Conversely, a ‘low risk’ score was given if no defects were identified, and an ‘unclear risk’ score was used when the available information was insufficient to determine the impact. The risk of bias assessment was conducted independently by two reviewers.
Statistical analysis
The overall effect sizes of apo in the niacin and control groups were calculated using the mean changes and their sd. In cases where mean changes were not reported, they were computed based on the changes in apo concentrations during the intervention. To ensure consistency, SE, 95 % CI and interquartile ranges were converted to sd using the method described by Hozo et al. (Reference Hozo, Djulbegovic and Hozo29)
For the analysis, a random-effects model was utilised, which accounts for between-study variations. The effect sizes for variables were expressed as weighted mean differences with their respective 95 % CI. Heterogeneity was assessed using the I2 statistic and Cochrane’s Q test. An I2 value greater than 50 % or a P value less than 0·05 for the Q-test indicated significant between-study heterogeneity. To explore potential sources of heterogeneity, we conducted subgroup analyses based on predefined variables, including intervention duration, type of niacin used, niacin dosage and origin country where the study was conducted.
To assess the possibility of publication bias, we conducted Egger’s and Begg’s regression tests. Furthermore, we conducted a non-linear dose–response analysis to examine the relationship between the pooled effect size and niacin dosage (mg/d) as well as the duration of the intervention (weeks). To ensure the strength of our findings, we performed a sensitivity analysis to identify if the overall effect size is influenced by any specific study. The meta-analysis was carried out using Stata, version 14 (StataCorp), and a significance level of P < 0·05 was considered statistically significant.
Certainty assessment
The overall certainty of evidence from the studies was evaluated based on the GRADE guidelines (Grading of Recommendations Assessment, Development, and Evaluation) working group. Using the corresponding evaluation criteria, the quality of evidence was categorised into four levels: high, moderate, low and very low(Reference Guyatt, Oxman and Vist30).
Results
Search results and study selection
In the initial phase of this meta-analysis, we identified a total of 1452 publications. After a thorough assessment, 585 articles were excluded due to duplication, and the study design of 800 articles did not meet the inclusion criteria as they encompassed animal studies, observational studies and review articles. Additionally, during the research process, we found four more articles through a comprehensive reference check of relevant studies. After careful screening of the remaining records, seventy-one publications were eligible for full-text assessment of eligibility. During this full-text assessment, thirty-five articles were further excluded as they did not meet the predefined inclusion criteria. Additionally, eighteen articles lacked a proper control group or placebo group, and six articles were excluded due to insufficient data for calculating the mean change and standard deviation of the mean change for our variables.
Ultimately, we included twelve clinical trials in this systematic review and meta-analysis. Among these studies, thirteen arms evaluated blood levels of apo B, and fourteen arms assessed blood levels of apo A1, as some trials involved multiple dosages or intervention durations. For a visual representation of the study selection process for inclusion in the systematic review, see the flowchart shown in Fig. 1.
Fig. 1. Flowchart of the study selection for inclusion in the systematic review and meta-analysis.
Characteristics of the included studies
Table 1 presents the characteristics of the RCT included in our current systematic review and meta-analysis. These trials were published between 1998 and 2017 and were conducted in various regions, including the USA(Reference Walldius, Jungner and Holme8,Reference Scoffone, Krajewski and Zorca22,Reference Superko, McGovern and Raul24,Reference Airan-Javia, Wolf and Wolfe31–Reference Investigators34) , UK(Reference Davoren, Kelly and Gries35,Reference Lee, Robson and Yu36) , Portugal(Reference Batuca, Amaral and Favas37), Pakistan(Reference Yasmeen, Dawani and Mahboob23), Korea(Reference Kim, Kim and Lee38) and Australia(Reference Hamilton, Chew and Davis18). All of these studies involved both male and female participants. The sample sizes of the included RCT varied significantly, ranging from fifteen to 3115 participants, resulting in a total sample size of 5634 individuals. The participants’ mean age across the studies ranged from 29 to 71 years. The niacin dosages administered in the trials ranged from 500 to 3000 mg/d and the duration of the intervention varied from 6 to 102·8 weeks.
Table 1. Summary of clinical trials on the effects of niacin on apo A1 and apo B levels
Int, intervention group; Con, control group; T2DM, type 2 diabetes mellitus; NAFLD, non-alcoholic fatty liver disease; NR, not reported.
Most of the studies utilised a parallel design for their interventions, except for one study(Reference Batuca, Amaral and Favas37) that employed a cross-over design. In terms of the type of niacin used, nine studies administered ERN(Reference Hamilton, Chew and Davis18,Reference Scoffone, Krajewski and Zorca22,Reference Superko, McGovern and Raul24,Reference Airan-Javia, Wolf and Wolfe31–Reference Investigators34,Reference Batuca, Amaral and Favas37) , one study used immediate-release niacin(Reference Superko, McGovern and Raul24), one used nicotinic acid(Reference Kim, Kim and Lee38), one used acipomax(Reference Davoren, Kelly and Gries35) and one study used modified release niacin(Reference Lee, Robson and Yu36). Additionally, four studies incorporated the use of statins(Reference Yasmeen, Dawani and Mahboob23,Reference Airan-Javia, Wolf and Wolfe31,Reference Investigators34) or n-3 fatty acids(Reference Savinova, Fillaus and Harris33) in conjunction with the main niacin intervention.
The RCT covered a diverse range of participant groups, including those with diabetes and metabolic syndrome(Reference Hamilton, Chew and Davis18,Reference Savinova, Fillaus and Harris33,Reference Davoren, Kelly and Gries35) , patients with dyslipidaemia(Reference Batuca, Amaral and Favas37,Reference Kim, Kim and Lee38) , non-alcoholic fatty liver disease(Reference Fabbrini, Mohammed and Korenblat32), CVD(Reference Superko, McGovern and Raul24,Reference Airan-Javia, Wolf and Wolfe31,Reference Investigators34,Reference Lee, Robson and Yu36) , sickle cell anaemia with low HDL levels(Reference Scoffone, Krajewski and Zorca22) and renal ischaemia(Reference Yasmeen, Dawani and Mahboob23).
According to the Cochrane Risk of Bias Assessment Tool, two studies obtained a high-quality rating(Reference Savinova, Fillaus and Harris33,Reference Kim, Kim and Lee38) , demonstrating a low risk of bias across all domains. On the other hand, two other studies were deemed moderate quality(Reference Davoren, Kelly and Gries35,Reference Lee, Robson and Yu36) , as they had one domain with an unclear risk of bias, and the other studies were considered high risk of bias(Reference Hamilton, Chew and Davis18,Reference Yasmeen, Dawani and Mahboob23,Reference Superko, McGovern and Raul24,Reference Airan-Javia, Wolf and Wolfe31,Reference Fabbrini, Mohammed and Korenblat32,Reference Investigators34,Reference Batuca, Amaral and Favas37) with at least one domain having a high risk of bias (Table 2).
Table 2. Methodological quality score for included studies using Cochrane quality assessment tool
Meta-analysis
The effect of niacin on apo B
The pooled analysis of thirteen effect sizes using a random-effects model revealed a significant reduction in apo B level with the use of niacin compared with the control group (weighted mean differences: −24·38, 95 % CI: −43·97, −4·78 mg/dl, P = 0·01). However, there was considerable heterogeneity among the included studies (test for heterogeneity: P < 0·001, I2 = 99·9 %) (Fig. 2). To explore the potential sources of heterogeneity, subgroup analyses were conducted based on the type of niacin, dosage, intervention duration and origin country (Table 3).
Fig. 2. Forest plot of a random effects meta-analysis of the effect of niacin on apo B. WMD, weighted mean difference
Table 3. Subgroup analyses of niacin effect on apo B and apo A1 levels
WMD, weighted mean difference.
Our findings revealed that the variation between studies could be attributed to dosage of niacin used. Based on these subgroup analyses, we observed a significant reduction in apo B concentrations with niacin intervention in RCT that had an intervention duration of ≤ 16 weeks compared with those with > 16 week (weighted mean differences: −21·8, 95 % CI: −29·33, −14·28 mg/dl, P: < 0·001). Subgroup analysis according to the dosage of intervention (< 2000 mg/d v. ≥ 2000 mg/d), type of niacin (ERN v. other forms of niacin) and origin country (USA v. other countries) showed a significant effect in all subgroups.
In the sensitivity analysis, the exclusion of any individual study did not impact the overall estimate for the effect of niacin on apo B concentrations (CI range: −46·74, −2·78). Additionally, based on the Begg’s test and Egger’s regression test, there was no substantial evidence of publication bias (P = 0·76 and 0·65, respectively). The dose–response analysis did not reveal any significant impact of niacin dose (P non-linearity = 0·49) and treatment duration (P non-linearity = 0·24) on apo B levels (Fig. 3(a) and (b)).
Fig. 3. Non-linear dose–response effects of niacin dosage (mg/d) on apo B (a), apo A1, (c) and treatment duration on apo B (b) apo A1(D). The 95 % CI is demonstrated in the shaded regions.
The effect of niacin on apo A1
The meta-analysis included data from twelve RCT and yielded thirteen effect sizes. The findings indicated that niacin had a significant increasing effect on apo A1 concentrations (weighted mean differences: 8·24, 95 % CI: 4·93, 11·54 mg/dl, P < 0·001), as illustrated in Fig. 4. Nevertheless, substantial heterogeneity was observed among the studies in this context (I2 = 90·4 %, P < 0·001) (Fig. 4).
Fig. 4. Forest plot of a random effects meta-analysis of the effect of niacin on apo A1. WMD, weighted mean difference.
Based on the subgroup analyses (Table 3), the variability between studies could be attributed to several factors, including the dosage and type of niacin administered, intervention duration and the country where the study was conducted. Notably, niacin resulted in a significant increase in Apo A1 concentrations in RCT that utilised ERN as the intervention, especially when the dosage of intervention exceeded 1500 mg/d. Furthermore, the effect of niacin administration was particularly significant in studies conducted in the USA compared with those conducted in other countries. The sensitivity analyses demonstrated that excluding any individual study did not substantially impact the estimated pooled effect size (CI range: 2·90, 12·90).
Based on the Begg’s test, no evidence of publication bias was observed (P = 0·82). However, Egger’s regression test indicated the potential presence of publication bias concerning the impact of niacin administration on apo A1 levels. Consequently, we applied the trim-and-fill method, but no studies were added, and the pooled effect size remained unchanged. The non-linear dose–response meta-analysis, which included thirteen eligible effect sizes focusing on apo A1 concentrations, revealed that neither niacin dosage nor intervention duration had a significant impact on serum apo A1 concentrations (P non-linearity = 0·18 and 0·50, respectively) (Fig. 3(c) and (d)).
Grading of evidence
An evaluation of the quality of evidence using the GRADE approach is presented in Table 4. Low quality of evidence was detected for apo B and apo A1 for a very serious inconsistency (I2 = 99·9 % and I2 = 90·4 % for heterogeneity, respectively).
Table 4. GRADE profile of niacin administration on apo B and apo A1
* There is high heterogeneity for apo B (I2 = 99·9 %) and apo A1 (I2 = 90·4 %).
Discussion
The current systematic review and meta-analysis aimed to assess the effects of niacin treatment on apo A1 and B. The results indicate that niacin intervention leads to a significant reduction in apo B levels and a significant increase in apo A1 concentrations. Niacin exerts its hypocholesterolemic effects through various mechanisms that affect lipid metabolism, including alterations in lipoprotein synthesis, lipolysis and clearance(Reference Fabbrini, Mohammed and Korenblat32,Reference Croyal, Ouguerram and Passard39) . By influencing these apo, niacin could play a crucial role in decreasing the risk of CVD(Reference Chapman, Redfern and McGovern40). However, it is essential to interpret these findings in light of the considerable heterogeneity observed among the included studies. Performing subgroup analyses revealed that the duration of niacin treatment significantly influenced its effect on apo B concentrations. Notably, niacin intervention for ≤ 16 weeks showed a more substantial reduction in apo B levels compared with interventions lasting > 16 weeks. This suggests that shorter-term use of niacin might be more effective in lowering apo B levels due to its immediate impact on lipid profiles. When niacin interventions extend beyond 16 weeks, they might trigger compensatory mechanisms that counteract the initial reduction in apo B levels. These mechanisms could entail alterations in receptor expression or cellular signalling pathways(Reference Santolla, De Francesco and Lappano41), ultimately diminishing niacin’s ability to lower apo B levels over time. Moreover, variations in patient adherence and compliance during longer interventions could play a role(Reference Beintner, Vollert and Zarski42). The subgroup analyses based on niacin dosage, type of niacin and origin country also indicated a significant effect in both subgroups. This suggests that regardless of the specific niacin type, dosage or country of origin, niacin consistently exerts a favourable impact on apo B levels. Regarding niacin effects on apo A1, subgroup analyses revealed that ERN was particularly effective in increasing apo A1 concentrations, especially at dosages exceeding 1500 mg/d. This suggests that the type and dosage of niacin could significantly influence its impact on apo A1 levels. It seems that as the dosage of niacin increases, its mechanisms of action might be more robustly engaged, leading to a greater stimulation of apo A1 synthesis and subsequently higher levels(Reference Zhang, Kamanna and Ganji43). However, the dose–response analysis in our meta-analysis did not show significant impacts of niacin dose on apo A1 levels. Additionally, the effect of niacin on apo A1 was more pronounced in studies conducted in the USA compared with those conducted in other countries. This observation could be attributed to differences in study populations, genetic factors, lifestyle or dietary habits across different geographical regions(Reference Volgman, Palaniappan and Aggarwal44). Moreover, the use of ERN in studies conducted in the USA, which seems more potent in influencing lipid particles, could be another contributing factor. This type of niacin stands as the most powerful pharmaceutical option currently used in clinical settings to elevate HDL-cholesterol levels by up to 35 %. Furthermore, ERN diminishes TAG levels, while it can modify both the size and quantity of LDL particles(Reference Birjmohun, Hutten and Kastelein45). Moreover, Sahebkar et al., in one systematic review and meta-analysis, showed that ERN could significantly reduce lipoprotein(a) levels(Reference Sahebkar, Reiner and Simental-Mendia46), another important risk factor for CVD(Reference Nordestgaard, Chapman and Ray47). The non-linear dose–response meta-analysis did not show any significant impact of niacin dosage or intervention duration on apo A1 levels. This suggests that within the range of dosages and intervention durations studied, increasing the dosage or duration of niacin treatment may not lead to a proportional increase in apo A1 concentrations.
The effects of niacin on apo A1 and B are closely related to its impact on lipoprotein metabolism. One of the primary mechanisms by which niacin improves lipid profile is by inhibiting the synthesis and secretion of VLDL particles from the liver(Reference Kamanna and Kashyap48,Reference Guo and Fisher49) . Niacin reduces the availability of free fatty acids in the liver, thereby diminishing the substrate for VLDL synthesis. As a result, there is a reduction in VLDL particle production, leading to decreased levels of TAG in the circulation(Reference Fabbrini, Mohammed and Korenblat32). Niacin also promotes the lipolysis of TAG within circulating VLDL and intermediate-density lipoprotein particles by activating lipoprotein lipase(Reference Kang, Kim and Youn50). Niacin could decrease the production of small, dense LDL particles, which are considered more atherogenic. It accomplishes this by reducing the activity of hepatic diacylglycerol acyltransferase-2, an enzyme involved in the synthesis of triglycerides within hepatocytes(Reference Hu, Chu and Yamashita51). Lower TAG availability results in the formation of larger, less atherogenic LDL particles. Additionally, niacin downregulates the expression of proprotein convertase subtilisin/kexin type 9, a protein that promotes the degradation of hepatic LDL receptors. The reduction in proprotein convertase subtilisin/kexin type 9 levels enhances LDL receptor recycling and increases LDL clearance from the circulation(Reference Warden, Minnier and Watts52,Reference Watts, Chan and Pang53) . Niacin reduces apo B levels by lowering the production of VLDL particles in the liver. Since each VLDL particle contains one molecule of apo B, the reduction in VLDL synthesis results in decreased apo B production(Reference Kamanna and Kashyap54). Additionally, Niacin increases HDL cholesterol levels by inhibiting the activity of cholesteryl ester transfer protein. Cholesteryl ester transfer protein facilitates the transfer of cholesteryl esters from HDL to other lipoproteins (such as VLDL and LDL) in exchange for TAG. By inhibiting cholesteryl ester transfer protein, niacin reduces the transfer of cholesteryl esters from HDL, thereby increasing HDL cholesterol levels. The rise in HDL levels is often accompanied by an increase in apo A1 as its major protein component(Reference Zhang, Kamanna and Ganji43,Reference Kamanna and Kashyap48) . These mechanisms collectively lead to improvements in lipid profile, including reductions in LDL-cholesterol and TAG, along with increases in HDL-cholesterol and apo A1 levels, while also reducing apo B levels.
This study represents the first systematic review and meta-analysis investigating the impact of niacin on apo A1 and B. Nonetheless, it is not without its limitations. First, the presence of substantial heterogeneity saw in meta-analysis could restrict the degree to which the findings can be generalised. The majority of included studies also had a high risk of bias. Moreover, another limitation of this meta-analysis stems from the inclusion of participants who encompass a variety of underlying pathological conditions, genetic backgrounds and lifestyle factors, which can cause difficulty in interpreting the outcomes derived from this systematic review and meta-analysis.
In conclusion, this systematic review and meta-analysis provide evidence that niacin treatment leads to a significant reduction in apo B levels and a significant increase in apo A1 concentrations. The results suggest that short-term niacin intervention may be more effective in reducing apo B levels, while ERN at higher dosages appears to be more effective in increasing apo A1 concentrations. However, the substantial heterogeneity among studies should be acknowledged as limitations that may affect the overall confidence in these findings. Further research and well-designed randomised controlled trials are needed to corroborate and refine these results and to better understand the optimal dosing and duration of niacin treatment for favourable effects on apo B and A1.
Acknowledgements
This work had no source of funding.
J. T., S. C. and P. S. T. designed and E. Y. R. and S. S. searched systematically for the study. E. Y. R. and S. S. reviewed and selected the articles and extracted data from articles. S. S. performed data analysis and interpretation. E. Y. R. and S. S. drafted the manuscript. S. C., J. T. and P. S. T. revised the article for important intellectual content.
The authors declare that there is no conflict of interest regarding the publication of this paper.
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
