TOXICOLOGY/CASE REPORT

Toxicity From the Use of Niacin to Beat Urine Drug Screening

Manoj K. Mittal, MD, MRCP
Todd Florin, MD
Jeanmarie Perrone, MD
João H. Delgado, MD
Kevin C. Osterhoudt, MD,
MSCE
From the Division of Emergency Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA
(Mittal, Osterhoudt); Department of Pediatrics (Mittal, Florin, Osterhoudt), and Department of
Emergency Medicine (Perrone), University of Pennsylvania School of Medicine, Philadelphia, PA;
and the Divisions of Emergency Medicine and Medical Toxicology, Hartford Hospital, Hartford, CT
(Delgado).

Niacin (vitamin B3) is promoted for rapidly clearing the body of drugs of abuse, such as cocaine and
cannabis, and is alleged to interfere with urine drug screening. We present 4 cases of such novel use
associated with significant adverse effects. Two cases had isolated skin manifestations, whereas the
other 2 presented with life-threatening manifestations, including nausea, vomiting, dizziness,
hepatotoxicity, metabolic acidosis, and hypoglycemia evolving into hyperglycemia. One patient also had
profound neutrophilia and QTC-interval prolongation. All patients improved after cessation of the drug
use and supportive treatment. Health care providers should be aware of these potential adverse effects
of niacin and of the misguided use of this vitamin by patients seeking to interfere with urine drug
screening. [Ann Emerg Med. 2007;50:587-590.]

0196-0644/$-see front matter

Copyright © 2007 by the American College of Emergency Physicians.
doi:10.1016/j.annemergmed.2007.01.014

SEE EDITORIAL, P. 591.
INTRODUCTION
Niacin is available by prescription and as an over-the-counter
food supplement. The recommended dietary intake of niacin is
14 to 16 mg per day.1 It is used for prevention and treatment of
niacin deficiency and in pharmacologic doses (1 to 5 g/day) to
treat hypercholesterolemia and hypertriglyceridemia.2 When
used pharmacologically, niacin has been associated with
multiple adverse effects, most typically skin flushing and
itching, as well as hepatotoxicity.3,4 Because niacin “promotes
metabolism” and is associated with flushing, some individuals
believe that taking large doses will produce a urine drug test
negative for various drugs of abuse, including cannabis and
cocaine.5 We report 4 patients who developed adverse reactions
to large doses of niacin taken with the intent of clearing their
bodies quickly of drugs of abuse. These patients were
encountered during 2 years in the emergency departments
(EDs) at 3 urban hospitals from a single university-based health
system and were identified by collaborative discussions among
the authors.
Two of the patients, a 23-year-old man and a 22-year-old
woman, abusers of cocaine and marijuana, respectively, took
niacin before a scheduled preemployment urine drug test. They
developed skin reactions involving flushing and burning
sensation in one patient and an itchy erythematous rash in the
other within minutes of ingesting niacin. The reactions subsided
spontaneously. The other 2 patients had more severe effects and
are described in more detail.
CASE REPORT
Patient 1
A previously healthy 14-year-old boy presented to the ED
with history of nausea, vomiting, upper abdominal pain,
palpitations, and dizziness for about 6 hours. He had 3 to 4
episodes of nonbloody and nonbilious emesis. There was no
history of chest pain, shortness of breath, fever, cough, nasal
congestion, diarrhea, or headache. He felt dizzy when getting up
from bed and when trying to walk. He admitted to smoking
marijuana for the preceding few weeks but denied any other
substance abuse, including ethanol or other toxic alcohols. He
did not display suicidal ideation. He was due to meet with his
parole officer on the day he became unwell. To beat his urine
drug test, he had ingested 11 500-mg tablets of timed-release
niacin (Goldline Laboratories, Fort Lauderdale, FL), totaling
5.5 g, during 36 hours before the onset of symptoms. He was
not taking any prescribed medication, and there was no other
significant personal or family medical history.
The patient was alert and cooperative but appeared unwell.
His vital signs were blood pressure 111/48 mm Hg, pulse rate
105 beats/min, respiratory rate 18 breaths/min, temperature
35.1°C (95.2°F), and SaO2 100%. His pupils were midposition
and reactive to light. His mucous membranes were slightly dry.
The rest of his examination results were unremarkable.

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Niacin Toxicity in Urine Drug Screening
Intravenous normal saline solution was administered. A CBC
showed hemoglobin 15.4 g/dL, WBC 54,000/␮L (76%
segmented neutrophils and 8% bands), and platelet count
529,000/␮L. A chemistry panel revealed sodium 144 mmol/L,
potassium 3.5 mmol/L, chloride 104 mmol/L, bicarbonate 13
mmol/L, blood urea nitrogen 7 mg/dL, creatinine 1.3 mg/dL,
and glucose 26 mg/dL. The patient was given 25 mL of 50%
dextrose intravenously to correct the hypoglycemia. The alanine
aminotransferase (ALT) and aspartate aminotransferase (AST)
levels were 92 IU/L (normal range: 10 to 45 IU/L) and 81 IU/L
(normal range: 15 to 40 IU/L), respectively. His arterial blood
gas analysis revealed pH 6.90, PaCO2 26 mm Hg, PaO2 119
mm Hg, and bicarbonate 6.3 mmol/L. The serum amylase and
lipase values were normal. His serum alcohol level was less than
5 mg/dL, and acetone was not detected in the serum. Urinalysis
was negative for glucose but had 2⫹ ketones. A screening urine
immunoassay test for amphetamines, barbiturates,
benzodiazepines, cocaine, and opiates was negative. Four hours
after presentation, his blood sugar level had increased to 183
mg/dL. The patient continued to vomit while in the ED but
otherwise remained stable. He was given a total of 1.3 L of
normal saline solution, 1 L of 5% dextrose in normal saline
solution, 25 mL of 50% dextrose, 50 mEq of sodium
bicarbonate, 12.5 mg of promethazine, 20 mg famotidine, and
3 g of ampicillin-sulbactam and was then transferred to a
tertiary care hospital.
On arrival to the tertiary care hospital ED 8 hours after
initial presentation, his vital signs were blood pressure 160/56
mm Hg, pulse rate 115 beats/min, respiratory rate 20 breaths/
min, temperature 37.7°C (99.9°F), and SaO2 100% in room
air. A venous blood gas test revealed pH 7.18, PaCO2 34.3 mm
Hg, PaO2 34.5 mm Hg, and bicarbonate 12.6 mmol/L. The
serum bicarbonate level had increased to 14 mmol/L and the
glucose level was 207 mg/dL. Serum salicylate and
acetaminophen tests were negative. His WBC count was now
71,300/␮L, with 82% segmented neutrophils and 9% band
forms. Urine analysis showed sugar level greater than 1 g/dL and
a small amount (15 mg/dL) of ketones. ECG revealed a QT
interval of 378 ms and a QTC of 511 ms. All other ECG values
were in the normal range. The blood glucose concentration
remained increased for the next 16 hours. A provisional
diagnosis of diabetic ketoacidosis was made; he began receiving
an insulin infusion and fluid repletion regimen.
Insulin infusion was weaned off after about 20 hours; his
blood sugar level remained normal thereafter without specific
treatment. The AST level peaked on day 3 of illness at 193
IU/L, whereas the ALT level peaked on day 4 at 344 IU/L. The
prothrombin time increased to a maximum of 18.8 seconds
(11-13.5 seconds) and International Normalized Ratio (INR) to
1.74 on day 3. On day 3, the WBC count was 18,300/␮L, the
serum bicarbonate was 25 mmol/L, and the QTC duration was
412 ms. A serum metformin level test was negative. His urine
was analyzed for drugs with gas chromatography/mass
588 Annals of Emergency Medicine
Mittal et al
spectrophotometry at a university-based toxicology laboratory,
and the results were negative except for cannabinoids.
Patient 2
A 17-year-old girl was brought to the hospital with history of
nausea, vomiting, and dizziness for 2 to 3 hours and
unresponsiveness for a few minutes before emergency medical
services were called. Fingerstick glucose level at the scene was 70
mg/dL. The patient was given naloxone 1 mg and 25 mL of
50% dextrose. The level of consciousness improved within a few
minutes. Repeated fingerstick glucose level was 222 mg/dL. On
arrival to the ED, she complained of feeling sleepy and cold.
There was no history of fever, headache, cough, cold, pain
abdomen, alteration of bowel habits, or of dysuria. The patient
had a history of asthma, anxiety, and depression and had been
prescribed medroxyprogesterone acetate and paroxetine
hydrochloride solution. She had been using marijuana and
“ecstasy” for a few months. She admitted ingesting 5 tablets of
niacin 500 mg (exact formulation unknown) throughout the
preceding 2 days to clear her urine of drugs of abuse. Her vital
signs were blood pressure 120/43 mm Hg, pulse rate 100 beats/
min, respiratory rate 32 breaths/min, temperature 34.4°C
(93.9°F), and SaO2 100% in room air. She was sleepy but fully
arousable. The pupils were of normal size and reacted to light
appropriately. She shivered intermittently. The rest of her
examination results were normal. Passive blanket rewarming
alleviated shivering and increased her temperature to 36.7°C
(98.1°F) during the next 2 hours. The laboratory results showed
WBC 9,700/␮L (48% neutrophils, 46% lymphocytes),
hemoglobin 14.6 g/dL, and platelets 335,000/␮L. Arterial blood
gas showed pH 7.32, PCO2 32 mm Hg, PO2 124 mm Hg, and
bicarbonate 16 mmol/L. The chemistry panel from blood taken
before administration of 50% dextrose revealed sodium 145
mmol/L, potassium 3.3 mmol/L, chloride 106 mmol/L,
bicarbonate 17.2 mmol/L, blood urea nitrogen 12 mg/dL,
creatinine 1 mg/dL, glucose 53 mg/dL, calcium 9.8 mg/dL,
bilirubin 1.3 mg/dL, AST 35 U/L, ALT 20 U/L, alkaline
phosphatase 89 IU/L, total protein 7.3 g/dL, and albumin 5
g/dL. The prothrombin time was 20.9 seconds (normal range:
10.3 to 12.8 seconds), with INR 3.1 and activated partial
thromboplastin time 23 seconds. The ammonia level was 15
␮mol/L (normal range: 11 to 45 ␮mol/L). Salicylate,
acetaminophen, and ethanol were not detectable in the blood.
Repeated testing on an ED blood sample showed a blood
glucose level of 187 mg/dL, prothrombin time of 23.1 seconds,
and an INR of 3.8. The urine toxicology screening
immunoassay result was negative for amphetamine, barbiturate,
benzodiazepines, cocaine, and opiates. The ECG result was
normal.
The patient was transferred to a tertiary care hospital, where
her vital signs were blood pressure 139/59 mm Hg, pulse rate
80 beats/min, respiratory rate 20 breaths/min, and temp 37.1°C
(98.8°F). She was nauseated and vomiting and showed evidence
of moderate dehydration. She was fully conscious, and the rest
of her examination results were normal. She was given
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Mittal et al
ondansetron 2 mg and continued on 0.9% saline solution with
potassium chloride 20 mEq/L intravenously. The blood glucose
level on arrival was 101 mg/dL. The only abnormal value in the
chemistry panel was bicarbonate 17 mmol/L. The CBC and
liver enzyme, amylase, lipase, and fibrinogen levels were normal.
The prothrombin time was 26.9 seconds, INR 2.73, and the
activated partial thromboplastin time 29.2 seconds. The blood
lactate level was 2.2 mmol/L (normal range: 0.5 to 2.2 mmol/L).
By the following day, the patient was no longer nauseated, and
her prothrombin time had improved to 23.4 seconds and the
INR to 2.29. The blood glucose values were 210 mg/dL and
183 mg/dL when they were checked on 2 occasions. She was
discharged, with arrangements for outpatient follow-up.
DISCUSSION
Various Internet forums promote the use of niacin to pass
urine drug tests. A Google (available at http://www.google.com)
search of the Internet for “pass urine drug test” ⫹ “niacin”
yielded 84,600 results. Many of these sites question the value of
niacin for these purposes and promote their own methods,
including various additives to urine and urine substitution
methods.
Niacin (nicotinic acid, nicotinamide, vitamin B3) is available
for oral use in immediate-release, sustained-release/long-acting,
and extended-release forms. We found 1 previous abstract
report of acute, intentional niacin overdose by 2 patients in an
effort to confound surveillance drug testing.6 As with our
patients, they had ingested sustained-release niacin. They
developed increased liver enzyme levels, a mild coagulopathy,
and a high-anion-gap metabolic acidosis, all of which resolved
within 72 hours of ingestion.6
Niacin is well known to cause skin flushing, a burning
sensation, a rash affecting mainly the face and the upper body,
and generalized pruritus within a few minutes of
administration.3,7 Two of our patients demonstrated this
reaction. Niacin-related flushing is more common with regular-
release niacin than with the sustained-release form8 and is
caused by prostaglandin-induced vasodilation.3 It is usually
self-limiting and does not need any specific treatment.3 In the
absence of an appropriate medical history, this reaction can be
misdiagnosed as anaphylaxis or hypersensitivity reaction and
treated inappropriately.9 Because it is prostaglandin-mediated, it
can be attenuated or prevented by the administration of
nonsteroidal anti-inflammatory agents.10
Two of our patients had severe reactions involving nausea,
vomiting, dizziness, and coagulopathy. The hepatic enzymes
were increased in patient 1 but not patient 2. Both patients had
initial hypoglycemia, which evolved into hyperglycemia, and
high-anion-gap metabolic acidosis. The combination of
abdominal pain, vomiting, hyperglycemia, glycosuria,
ketonuria, and high-anion-gap metabolic acidosis in patient 1
resulted in a misdiagnosis of diabetic ketoacidosis. This patient
had impressive neutrophilia. Both patients improved during a
few days with supportive care.
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Niacin Toxicity in Urine Drug Screening
Niacin is associated with gastrointestinal upset, including
vomiting,7 headache,8 lightheadedness, and hypotension.11 In
high doses, it has been reported to cause liver injury that usually
resolves spontaneously once the drug is withdrawn.4,8,12-14
Rarely, however, niacin can cause acute liver failure, warranting
liver transplant.15 Most reported patients with niacin-induced
coagulopathy have had markedly increased liver enzyme levels;
however, there are some reports in which patients with
coagulopathy had only mild increase of liver enzyme levels.13,14
Sustained-release preparations of niacin, especially the
sustained-release/long-acting forms, are implicated more often
than crystalline preparations (immediate release) in patients who
develop gastrointestinal upset or hepatitis.13-15
We believe that the puzzling dysglycemia exhibited by our
patients can be explained by niacin overdose. Niacin has 2
prominent metabolic effects in addition to its cholesterol- and
lipid-lowering properties: It inhibits lipolysis and induces
insulin resistance.16 Both patients had vomited for several hours
before arrival. As a result, their metabolic state would be
consistent with a fasting state. As glycogen stores become
depleted, glucagon and epinephrine are released in response to
decreasing circulating glucose and stimulate gluconeogenesis.
Circulating free fatty acids resulting from lipolysis provide a key
substrate to the liver for gluconeogenesis during fasting. The
combination of glycogen store depletion from prolonged
vomiting and inhibition of lipolysis by niacin may explain the
initial hypoglycemia observed in these patients. Correction
of hypoglycemia with dextrose in these patients then
“unmasked” the niacin-induced insulin resistance. The ensuing
hyperglycemia is most likely due to an exaggerated
pharmacologic effect arising from supratherapeutic niacin levels.
Metabolic acidosis and lactic acidosis have also been reported
in association with high-dose niacin therapy.11,17,18
Unfortunately, lactic acid levels were not checked on patient 1
when he was acidemic. However, most other plausible causes of
increased anion-gap metabolic acidosis were excluded. The
fourth patient had a high-normal value of lactate associated with
the moderate metabolic acidosis.
We did not find reports in the literature about the
association of niacin with the marked neutrophilia evident in
our patient or with prolongation of QTC interval on the ECG.
Leukocytosis has been noticed previously with niacin toxicity,
typically in the setting of metabolic acidosis, but not to the
extent our patient experienced.17,18 The prolonged QTC
interval is probably related to the patient’s severe metabolic
acidosis. QTC-interval prolongation has been reported in
children receiving ketogenic diets, in which degree of acidosis
correlated with QTC duration.19
We contend that our patients’ illnesses were due to niacin
toxicity, considering that they provided a history of high-dose
niacin ingestion temporally associated with the illness and that
neither history nor urine and serum toxicology analysis provided
another toxicologic explanation for the illness. In addition, the
gastrointestinal symptoms, metabolic acidosis, hyperglycemia,
Annals of Emergency Medicine 589
Niacin Toxicity in Urine Drug Screening
and hepatitis are consistent with previous reports of niacin
toxicity. No other infectious, endocrine, or metabolic
explanation for the illness was discovered, and both patients
recovered quickly once further niacin intake was stopped.
SUMMARY
With the proliferation of urine drug testing by prospective
employers and various government agencies, more patients with
niacin toxicity may present to EDs. Health care providers,
especially physicians practicing emergency medicine, and
toxicologists are encouraged to be aware of these potential
adverse effects of niacin when it is used in pharmacologic doses.
Supervising editor: Richard C. Dart, MD, PhD
Funding and support: By Annals policy, all authors are required
to disclose any and all commercial, financial, and other
relationships in any way related to the subject of this article,
that may create any potential conflict of interest. The authors
have stated that no such relationships exist. See the
Manuscript Submission Agreement in this issue for examples
of specific conflicts covered by this statement.
Publication dates: Received for publication October 28, 2006.
Revisions received November 29, 2006, and January 3, 2007.
Accepted for publication January 19, 2007. Available online
April 5, 2007.
Presented at the 8th Annual Clinical Pathological Case
Presentation Competition, 2006 North American Congress of
Clinical Toxicology (NACCT) meeting, October 2006, San
Francisco, CA.
Reprints not available from the authors.
Address for correspondence: Manoj K. Mittal, MD, MRCP,
Division of Emergency Medicine, The Children’s Hospital of
Philadelphia, 34th Street and Civic Center Boulevard,
Philadelphia, PA 19104-4399; 215-590-1944, fax 215-590-
4454; E-mail manojmital@yahoo.com.
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Did you know?
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590 Annals of Emergency Medicine
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