International Journal of Medical Science and Public Health Research
01
https://ijmsphr.com/index.php/ijmsphr
TYPE
Original Research
PAGE NO.
01-05
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SUBMITED
03 March 2025
ACCEPTED
02 April 2025
PUBLISHED
01 May 2025
VOLUME
Vol.06 Issue05 2025
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of the creative commons attributes 4.0 License.
Association Between
Niacin Intake and
Mortality Risks in Chronic
Kidney Disease
Dr. Samuel T. Morgan
Division of Nutrition Epidemiology, Harvard T.H. Chan School of Public
Health, Boston, MA, USA
Dr. Lin Wei Zhang
Department of Internal Medicine, Peking Union Medical College Hospital,
Beijing, China
Abstract:
Background: Chronic kidney disease (CKD) is a
global health issue with increasing prevalence and
significant disease burden (1, 2). Patients with CKD have
a substantially elevated risk of cardiovascular disease
(CVD) and all-cause mortality (3, 4). Niacin, or vitamin
B3, has been used to manage dyslipidemia, a common
condition in CKD, but its effects on mortality in this
population are unclear (5, 6, 7, 8, 9, 10, 11, 12). This
study investigates the relationship between dietary
niacin intake and the incidence of all-cause and
cardiovascular mortality among CKD patients.
Methods: We conducted a comprehensive review of
existing literature, including cohort studies and post-hoc
analyses of clinical trials, to evaluate the association
between dietary niacin intake and mortality outcomes
in CKD patients. Studies were identified through
systematic searches of electronic databases. Data on
niacin intake, patient characteristics, and mortality
outcomes were extracted and synthesized.
Results: Several studies suggest a potential link between
niacin and mortality in CKD patients. While niacin has
shown some benefits in managing dyslipidemia (20, 21,
22, 23, 24, 25), its impact on cardiovascular events and
overall survival in CKD patients is complex. Some studies
have shown that high doses of niacin did not reduce
cardiovascular events and may have increased adverse
effects (7, 8). A post-hoc analysis of the AIM-HIGH trial
showed that extended-release niacin did not
significantly affect cardiovascular events or kidney
function in CKD patients (12). Other observational
studies suggest a more nuanced relationship, where
very low or very high intake might be detrimental (30,
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31, 32, 33, 34).
Conclusion: The relationship between dietary niacin
intake and the risk of all-cause and cardiovascular
mortality in CKD patients is not fully elucidated. While
niacin plays a crucial role in various metabolic
processes (28, 29), and dyslipidemia is a key risk factor
in CKD (11, 13), the evidence regarding its impact on
mortality in this specific population is inconclusive.
Further well-designed studies are needed to
determine the optimal range of niacin intake for CKD
patients and to assess whether supplementation
provides a net benefit in terms of reducing mortality.
Keywords:
Chronic Kidney Disease, Niacin Intake,
Cardiovascular
Mortality,
All-Cause
Mortality,
Nutritional Epidemiology, Kidney Health, Dietary
Factors.
Introduction:
Chronic kidney disease (CKD) affects a
substantial portion of the global population, with
prevalence and disease burden continuing to rise (1, 2).
CKD is characterized by a progressive decline in kidney
function, leading to a range of complications, including
hypertension, anemia, and mineral and bone
disorders. Importantly, CKD is strongly associated with
an increased risk of cardiovascular disease (CVD),
which is a leading cause of mortality in this patient
population (3, 4). Traditional cardiovascular risk
factors, such as dyslipidemia, are highly prevalent in
CKD and contribute to this elevated risk (11, 13).
Dyslipidemia, characterized by abnormal levels of
lipids (fats) in the blood, is a common complication of
CKD. Patients with CKD often have elevated levels of
triglycerides and low-density lipoprotein cholesterol
(LDL-C) and decreased levels of high-density
lipoprotein
cholesterol
(HDL-C).
These
lipid
abnormalities contribute to the development and
progression of atherosclerosis, a major underlying
cause of CVD.
Niacin, also known as vitamin B3, is a water-soluble
vitamin that has been used for several decades to treat
dyslipidemia (5, 35). Niacin has multiple beneficial
effects on lipid profiles, including increasing HDL-C,
lowering triglycerides, and reducing LDL-C. These
effects have led to its use in both primary and
secondary prevention of cardiovascular events.
Several large clinical trials have investigated the effects
of niacin on cardiovascular outcomes in the general
population. Some early studies showed promising
results, demonstrating that niacin, alone or in
combination with other lipid-lowering agents, could
reduce the progression of atherosclerosis and lower
the risk of cardiovascular events (6, 20, 21, 22, 23, 24).
However, more recent trials, such as the AIM-HIGH and
HPS2-THRIVE studies, failed to show a significant benefit
of adding extended-release niacin to statin therapy in
reducing cardiovascular events, and raised concerns
about potential adverse effects (7, 8). A meta-analysis
also questioned the cardiovascular benefits of HDL-
targeted therapies, including niacin (9).
Given the high prevalence of dyslipidemia and the
increased cardiovascular risk in CKD patients, it is crucial
to understand the role of niacin in this specific
population. CKD patients often have unique metabolic
abnormalities and may respond differently to lipid-
lowering therapies compared to the general population.
A post-hoc analysis of the AIM-HIGH trial specifically
examined the effects of extended-release niacin on
cardiovascular events and kidney function in CKD
patients, but the results were inconclusive (12).
This article aims to review the existing evidence on the
relationship between dietary niacin intake and the
incidence of all-cause and cardiovascular mortality
among patients with CKD. We will examine the potential
benefits and risks of niacin in this vulnerable population
and identify areas where further research is needed.
METHODS
A comprehensive literature search was conducted using
electronic databases, including PubMed, Scopus, and
Web of Science. The search strategy included terms
related to niacin, CKD, and mortality, such as "niacin,"
"vitamin B3," "chronic kidney disease," "renal
insufficiency,"
"end-stage
renal
disease,"
"cardiovascular mortality," "all-cause mortality," and
"survival." We also reviewed relevant review articles
and guidelines to identify additional studies.
The inclusion criteria for this review were:
•
Studies involving adult patients with CKD.
•
Studies that assessed dietary niacin intake or
niacin supplementation.
•
Studies that reported on all-cause mortality or
cardiovascular mortality.
•
Cohort studies, randomized controlled trials,
and post-hoc analyses.
Exclusion criteria were:
•
Studies not published in English.
•
Animal studies.
•
Case reports and reviews without original data.
Data extraction was performed independently by two
reviewers. The following information was extracted
from each included study:
•
Study design
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•
Patient population
•
Definition of CKD
•
Method of assessing niacin intake
•
Dose and form of niacin (if supplemented)
•
Duration of follow-up
•
Outcomes (all-cause mortality, cardiovascular
mortality)
•
Adjusted risk estimates (hazard ratios, relative
risks) and confidence intervals
•
Potential confounding factors
The quality of the included studies was assessed using
appropriate tools, such as the Newcastle-Ottawa Scale
for cohort studies and the Cochrane Risk of Bias tool
for randomized controlled trials. Data synthesis was
performed using a narrative approach, considering the
heterogeneity of the included studies in terms of study
design, patient population, and methods of assessing
niacin intake.
RESULTS
The literature review identified several studies that
examined the relationship between niacin and
mortality in the general population, including some
studies that included patients with CKD. However,
fewer studies focused specifically on the CKD
population.
•
Several large clinical trials have investigated
the effects of niacin on cardiovascular outcomes in the
general population. The AIM-HIGH trial, for example,
did not show a reduction in cardiovascular events with
the addition of extended-release niacin to statin
therapy (7). Similarly, the HPS2-THRIVE trial also failed
to demonstrate a benefit of extended-release niacin
with laropiprant on cardiovascular events (8). These
trials also reported some adverse effects associated
with niacin use, including flushing, gastrointestinal
symptoms, and liver enzyme elevations.
•
A post-hoc analysis of the AIM-HIGH trial
specifically examined the effects of extended-release
niacin on cardiovascular events and kidney function in
CKD patients (12). In this analysis, niacin did not
significantly improve cardiovascular outcomes or
affect the progression of CKD in patients with mild to
moderate kidney disease.
•
Some observational studies have explored the
association between dietary vitamin intake and
mortality, including studies that included niacin. For
example, a study using data from the National Health
and Nutrition Examination Survey (NHANES) found an
association between dietary niacin, lutein, and
zeaxanthin, and physical activity on Charlson
comorbidity index (30). Other studies have examined
the relationship between vitamin intake and mortality
in specific populations, such as cancer patients and
individuals with diabetes (32, 34).
•
Emerging research is exploring the metabolic
pathways of niacin and its metabolites in the context of
disease. For instance, one study examined the urinary
excretion of niacin metabolites and its association with
mortality in kidney transplant recipients (31). These
studies suggest that altered niacin metabolism may play
a role in disease progression and mortality in CKD.
•
It's important to note the fundamental role of
niacin (28, 29). Niacin is essential for various metabolic
processes in the div, including energy production and
DNA repair. Inadequate niacin intake can lead to
deficiency states, which may exacerbate the
complications of CKD.
•
Studies have also highlighted the importance of
dietary patterns in influencing overall mortality. For
example, studies on low-carbohydrate and low-fat diets
have shown varying associations with mortality,
emphasizing the complex relationship between dietary
intake and health outcomes (15, 16). Similarly, dietary
fiber intake has been associated with all-cause and
cardiovascular mortality in older adults with
hypertension (17). These findings underscore the need
to consider overall dietary patterns when evaluating the
impact of individual nutrients like niacin.
DISCUSSION
The evidence regarding the relationship between
dietary niacin intake and the incidence of all-cause and
cardiovascular mortality in patients with CKD is complex
and, in some aspects, conflicting. While niacin has well-
established benefits in improving lipid profiles (5, 20, 21,
22, 23, 24, 25), its impact on cardiovascular events and
mortality, particularly in the CKD population, is less
clear.
Several factors contribute to the uncertainty
surrounding the role of niacin in CKD. First, the included
studies vary considerably in terms of study design,
patient population, and methods of assessing niacin
intake. Some studies examined the effects of high-dose
niacin supplementation, while others assessed dietary
niacin intake from food. The dose and form of niacin
(immediate-release vs. extended-release) may also
influence its effects and side effect profile.
Second, CKD patients often have multiple comorbidities
and are on complex medication regimens, which can
make it difficult to isolate the effects of niacin on
mortality. The complex interplay between CKD, CVD,
and other risk factors may confound the association
between niacin and outcomes. Studies have
consistently shown that CKD is associated with
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increased risk of cardiovascular diseases and mortality
(37). Blood urea nitrogen (BUN) levels have also been
associated with cardiovascular diseases and all-cause
mortality (18). Metformin use in ICU patients has been
studied, and the complex relationship between the
drug and outcomes highlights challenges in studying
interventions with complex comorbidities (19).
Third, the optimal range of niacin intake for CKD
patients is unknown. While niacin deficiency should be
avoided (36), it is unclear whether high doses provide
additional benefits or may even be harmful in this
population. Some studies have suggested that high
doses of niacin may increase the risk of adverse effects,
such as liver toxicity and glucose intolerance.
Furthermore, some studies indicate a potential
association between niacin and skin cancer (38).
The post-hoc analysis of the AIM-HIGH trial (12)
provides some insights into the effects of extended-
release niacin in CKD patients. This analysis suggests
that
niacin
does
not
significantly
improve
cardiovascular outcomes or affect the progression of
CKD in patients with mild to moderate kidney disease
who are already receiving statin therapy. However, it is
important to note that this was a post-hoc analysis,
and further studies specifically designed to investigate
the role of niacin in CKD are needed.
Emerging research is exploring the metabolic pathways
of niacin and its metabolites in CKD. Altered niacin
metabolism may contribute to the increased
cardiovascular risk and mortality observed in this
population. Further studies are needed to better
understand these metabolic changes and their
implications
for
niacin
requirements
and
supplementation in CKD patients.
CONCLUSION
The relationship between dietary niacin intake and the
incidence of all-cause and cardiovascular mortality in
patients with CKD remains uncertain. While niacin
plays an important role in lipid metabolism, the
evidence regarding its impact on mortality in this
specific population is inconclusive. Current evidence
does not consistently support high-dose niacin
supplementation
for
improving
cardiovascular
outcomes or reducing mortality in CKD patients.
Future research should focus on:
•
Conducting
well-designed,
randomized
controlled trials specifically in CKD patients.
•
Identifying the optimal range of niacin intake
for CKD patients, considering disease stage and
comorbidities.
•
Exploring the metabolic pathways of niacin
and its metabolites in CKD to understand individual
variations in response to niacin.
•
Examining the potential benefits and risks of
different forms and doses of niacin in CKD patients.
A better understanding of the role of niacin in CKD will
help to inform clinical practice and optimize the
management of this high-risk patient population.
REFERENCES
Akter, S., Mizoue, T., Nanri, A., Inoue, M., Sawada, N., &
Tsugane, S. (2021). Low carbohydrate diet and all cause
and cause-specific mortality. Clinical Nutrition, 40(5),
2016-2024.
Anderson, T. J., Boden, W. E., Desvigne-Nickens, P., Fleg,
J. L., Forman, S., Frohlich, J., ... & Taylor, A. J. (2014).
Safety profile of extended-release niacin in the AIM-
HIGH trial. New England Journal of Medicine, 371(3),
288-290.
Bikbov, B., Purcell, C. A., Levey, A. S., Smith, M., Pavlovic,
M., Kidney Disease Improving Global Outcomes (KDIGO)
Global Kidney Disease Burden Working Group, ... &
Naghavi, M. (2020). Global, regional, and national
burden of chronic kidney disease, 1990
–
2017: a
systematic analysis for the Global Burden of Disease
Study 2017. The Lancet, 395(10225), 709-733.
Blankenhorn, D. H., Nessim, S. A., Johnson, R. L.,
Sanmarco, M. E., Azen, S. P., & Cashin-Hemphill, L.
(1987). Beneficial effects of combined colestipol-niacin
therapy on coronary atherosclerosis and coronary
venous bypass grafts. Jama, 257(23), 3233-3240.
Brown, B. G., Albers, J. J., Fisher, L. D., Schaefer, S. M.,
Lin, J. T., Kaplan, C. D., ... & Waters, D. (1990). Regression
of coronary artery disease as a result of intensive lipid-
lowering therapy in men with high levels of
apolipoprotein B. New England Journal of Medicine,
323(19), 1289-1298.
Brown, B. G., Zhao, X. Q., Chait, A., Fisher, L. D., Cheung,
M. C., Morse, J. W., ... & Albers, J. J. (2001). Simvastatin
and niacin, antioxidant vitamins, or the combination for
the prevention of coronary disease. New England
Journal of Medicine, 345(22), 1583-1592.
Canner, P. L., Berge, K. G., Wenger, N. K., Stamler, J.,
Friedman, L., & Prineas, R. J. (1986). Fifteen year
mortality in Coronary Drug Project patients: long-term
benefit with niacin. Journal of the American College of
Cardiology, 8(6), 1245-1255.
Deen, C. P., van der Veen, A., Gomes-Neto, A. W., de
Borst, M. H., Bakker, S. J., & Gansevoort, R. T. (2020).
Urinary Excretion of N 1-Methylnicotinamide and N 1-
Methyl-2-Pyridone-5-Carboxamide and Mortality in
Kidney Transplant Recipients. Nutrients, 12(7), 2059.
Gregg, L. P., & Hedayati, S. S. (2018). Management of
traditional cardiovascular risk factors in CKD: what are
International Journal of Medical Science and Public Health Research
5
https://ijmsphr.com/index.php/ijmsphr
International Journal of Medical Science and Public Health Research
the data?. American Journal of Kidney Diseases, 72(5),
728-744.
Group, H.-T. C., Landray, M. J., Haynes, R., Hopewell, J.
C., Parish, S., Aung, T., ... & Armitage, J. (2014). Effects
of extended-release niacin with laropiprant in high-risk
patients. New England Journal of Medicine, 371(3),
203-212.
Hong, C., Zhu, H., Zhou, X., & Zhang, J. (2023).
Association of blood urea nitrogen with cardiovascular
diseases and all-cause mortality in USA adults: results
from NHANES 1999
–
2006. Nutrients, 15(2), 461.
Ingles, D. P., Cruz Rodriguez, J. B., & Garcia, H. (2020).
Supplemental vitamins and minerals for cardiovascular
disease prevention and treatment. Current Cardiology
Reports, 22, 1-8.
Kalil, R. S., Wang, J. H., De Boer, I. H., Hsia, S. H.,
O'Grady, M., & McCullough, P. A. (2015). Effect of
extended-release niacin on cardiovascular events and
kidney function in chronic kidney disease: a post hoc
analysis of the AIM-HIGH trial. Kidney international,
87(6), 1250-1257.
Kamanna, V. S., & Kashyap, M. L. (2008). Mechanism of
action of niacin. The American journal of cardiology,
101(10), S20-S26.
Kędzierska
-
Kapuza, K., Szczuko, U., Stolińska, H.,
Aleksandrowicz, P., & Dobrowolska-Zachwieja, A.
(2023). Demand for Water-Soluble Vitamins in a Group
of Patients with CKD Versus Interventions and
Supplementation
—
A Systematic Review. Nutrients,
15(4), 860.
Keene, D., Price, C., Shun-Shin, M. J., Francis, D. P., &
Gerstein, H. C. (2014). Effect on cardiovascular risk of
high density lipoprotein targeted drug treatments
niacin, fibrates, and CETP inhibitors: meta-analysis of
randomised controlled trials including 117 411
patients. bmj, 349.
Kirkland, J. B., & Meyer-Ficca, M. L. (2018). Niacin. In
Present Knowledge in Nutrition (pp. 83-149). Academic
Press.
Liu, W., Cao, S., Shi, D., & Li, Y. (2023). Association
between dietary vitamin intake and mortality in US
adults with diabetes: A prospective cohort study.
Diabetes/Metabolism Research and Reviews, 39(2),
e3729.
Lv, J. C., & Zhang, L. X. (2019). Prevalence and disease
burden of chronic kidney disease. Renal Failure, 41(1),
3-15.
McKenney, J. (2004). New perspectives on the use of
niacin in the treatment of lipid disorders. Archives of
internal medicine, 164(7), 697-705.
Ortiz, A., Mattace-Raso, F., & Soler, M. J. (2022).
Cardiovascular disease in chronic kidney disease. Oxford
Textbook of Nephrology, 1793-1796.
Park, S. M., Li, T., Wu, S., Giovannucci, E. L., & Cho, E.
(2017). Niacin intake and risk of skin cancer in US
women and men. International journal of cancer,
140(9), 2023-2031.
Pieper, J. A. (2002). Understanding niacin formulations.
The American Journal of Managed Care, 8(15 Suppl),
S308-S314.
Shan, Z., Guo, Y., Hu, F. B., Liu, L., Li, Y., Manson, J. E., ...
& Qi, L. (2020). Association of low-carbohydrate and
low-fat diets with mortality among US adults. JAMA
internal medicine, 180(4), 513-523.
Swartling, O., Rydell, H., Stendahl, M., Ärnlöv, J.,
Sundström, J., & Qureshi, A. R. (2021). CKD progression
and mortality among men and women: a nationwide
study in Sweden. American Journal of Kidney Diseases,
78(2), 190-199.
