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A Pilot Study of Chromium Picolinate for Weight Loss

Authors:

Abstract

Chromium is an essential trace element and nutritional supplement that has garnered interest for use as a weight loss aid. This trial assesses the effects of chromium picolinate supplementation, alone and combined with nutritional education, on weight loss in apparently healthy overweight adults. This was a randomized, double-blind, placebo-controlled trial of 80 otherwise healthy, overweight adults assessed at baseline for central adiposity measured by computerized tomography. Subjects were randomly assigned to daily ingestion of 1000 microg of chromium picolinate or placebo for 24 weeks. All subjects received passive nutritional education at the 12-week point in both the intervention and control groups. Outcomes include weight, height, blood pressure, percent body fat, serum, and urinary biomarkers. At baseline, both the chromium and placebo groups had similar mean body mass index (BMI) (chromium = 36 +/- 6.7 kg/m(2) versus placebo = 36.1 +/- 7.6 kg/m(2); p = 0.98). After 12 weeks, no change was seen in BMI in the intervention as compared to placebo (chromium = 0.3 +/- 0.8 kg/m(2) versus placebo = 0.0 +/- 0.4 kg/m(2); p = 0.07). No change was seen in BMI after 24 weeks in the intervention as compared to placebo (chromium = 0.1 +/- 0.2 kg/m(2) versus placebo = 0.0 +/- 0.5 kg/m(2); p = 0.81). Variation in central adiposity did not affect any outcome measures. Supplementation of 1000 microg of chromium picolinate alone, and in combination with nutritional education, did not affect weight loss in this population of overweight adults. Response to chromium did not vary with central adiposity.
A Pilot Study of Chromium Picolinate for Weight Loss
Yuka Yazaki, N.D.,
1
Zubaida Faridi, M.B.B.S., M.P.H.,
1
Yingying Ma, M.D., M.S.,
1
Ather Ali, N.D., M.P.H.,
1,2
Veronika Northrup, M.P.H.,
1,2
Valentine Yanchou Njike, M.D.,
1
Lauren Liberti, M.S.,
1,2
and David L. Katz, M.D., M.P.H.
1,2
Abstract
Background: Chromium is an essential trace element and nutritional supplement that has garnered interest for
use as a weight loss aid.
Objective: This trial assesses the effects of chromium picolinate supplementation, alone and combined with
nutritional education, on weight loss in apparently healthy overweight adults.
Design: This was a randomized, double-blind, placebo-controlled trial of 80 otherwise healthy, overweight
adults assessed at baseline for central adiposity measured by computerized tomography. Subjects were ran-
domly assigned to daily ingestion of 1000 mg of chromium picolinate or placebo for 24 weeks. All subjects
received passive nutritional education at the 12-week point in both the intervention and control groups. Out-
comes include weight, height, blood pressure, percent body fat, serum, and urinary biomarkers.
Results: At baseline, both the chromium and placebo groups had similar mean body mass index (BMI)
(chromium ¼36 6.7 kg=m
2
versus placebo ¼36.1 7.6 kg=m
2
;p¼0.98). After 12 weeks, no change was seen in
BMI in the intervention as compared to placebo (chromium ¼0.3 0.8 kg=m
2
versus placebo ¼0.0 0.4 kg=m
2
;
p¼0.07). No change was seen in BMI after 24 weeks in the intervention as compared to placebo
(chromium ¼0.1 0.2 kg=m
2
versus placebo ¼0.0 0.5 kg=m
2
;p¼0.81). Variation in central adiposity did not
affect any outcome measures.
Conclusions: Supplementation of 1000 mg of chromium picolinate alone, and in combination with nutritional
education, did not affect weight loss in this population of overweight adults. Response to chromium did not
vary with central adiposity.
Introduction
Over 65% of adults in the United States are overweight
or obese, defined as a body mass index (BMI) at or above
25 or 30 kg=m
2
, respectively.
1–3
The health consequences of
obesity are well characterized.
4
A strong relationship exists
between BMI and all-cause mortality
5,6
; obesity contributes
substantially to cardiovascular risk,
7–9
and excess body
weight is a potent risk factor for most cancers.
10,11
Consider-
ing the health consequences of obesity, there is a growing
need for safe and effective aids to weight loss.
The Nutrition Business Journal reported that supplement
sales grew from $8.6 to $23.7 billion between 1994 and
2007.
12
Sports nutrition and weight loss supplements ac-
counted for approximately 27% of total sales.
13–15
Despite the growing consumer market for use of dietary
supplements, efficacy in weight loss remains unsubstanti-
ated. A 2004 systematic review concluded that the evidence
for most dietary supplements as aids in reducing body
weight is inconclusive.
16
A notable exception is ephedra,
found to be an effective weight loss aid,
17
though banned
from the market by the U.S. Food and Drug Administration
in 2004 due to safety concerns.
12
Chromium is an essential trace element and nutritional
supplement that has garnered interest for use as a weight
loss aid.
18
Purported benefits of supplementation include
increased lean body mass, decreased body fat, and greater
resting energy expenditure.
19
Chromium has been thought to be the active ingredient in
glucose tolerance factor, a complex of molecules that in-
cludes glycine, cysteine, glutamic acid, nicotinic acid, and
chromium.
20
This complex of molecules found in high
amounts in brewer’s yeast and other foods functions syner-
gistically to potentiate the effects of insulin
21–23
by increasing
insulin binding to cells, upregulating receptors, and improv-
ing affinity.
24
Some reports suggest that chromium could
1
Yale-Griffin Prevention Research Center, Derby, CT.
2
Yale University School of Medicine, New Haven, CT.
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
Volume 16, Number 3, 2010, pp. 291–299
ªMary Ann Liebert, Inc.
DOI: 10.1089=acm.2009.0286
291
suppress appetite and stimulate thermogenesis through
sensitization of insulin-sensitive glucoreceptors in the brain.
25
Body fat distribution is related to insulin sensitivity; pe-
ripheral fat is more insulin sensitive than central fat found in
the chest and abdomen.
26
A meta-analysis of 10 double-blind, placebo-controlled
trials provides evidence of a relatively small reduction in
body weight (1.1–1.2 kg over 10–13 weeks) in overweight
and obese individuals receiving chromium picolinate.
27
This trial was designed to assess the effects of chromium
picolinate supplementation alone and combined with a nu-
trition education intervention on weight loss in both men
and women, and to assess any effects attributable to an-
thropometry (body fat distribution).
Methods
Participants
A total of 80 adults (40 female and 40 male) were recruited
from the Lower Naugatuck Valley, CT, through newspaper
advertisements and posters in medical offices affiliated with
Griffin Hospital (Fig. 1). All participants were overweight
(body–mass index [BMI] >25 kg=m
2
) nonsmoking adults
ages 25–75 with abdominal adiposity (waist circumference
>80 cm in females and >100 cm in males).
28
Exclusion criteria
included contraindication to abdominal computed tomo-
graphy (CT) scans (weight >375 pounds, claustrophobia,
unstable vital signs, or radiation procedure in past 6 months),
diagnosed diabetes, diagnosed eating disorder, uncontrolled
hypertension, emphysema, intestinal or stomach disease, kid-
ney disease (serum creatinine >2), substance abuse, preg-
nancy, or intention to become pregnant during the study.
Those meeting initial prescreening criteria (n¼156) un-
derwent clinical screening examination consisting of height,
weight, BMI, blood pressure, and waist–hip measurements
and blood profiles inclusive of lipid panel (total cholesterol,
high-density lipoprotein [HDL], low-density lipoprotein
[LDL] and triglycerides), comprehensive metabolic panel,
fasting plasma glucose, fasting insulin, C-reactive protein, and
lipoprotein-associated phospholipase A2 (Lp-PLA2). In ad-
dition, percent body fat was recorded via bioelectrical im-
pedance using the Bio Analogics ELGII Health Management
System (HMS; www.bioanalogics.com). A urine pregnancy
test for human chorionic gonadotropin was performed on
female patients to ascertain nonpregnant status at baseline.
The study protocol and consent form were approved by
the Griffin Hospital (Derby, CT) Institutional Review Board
and the Yale University (New Haven, CT) Human In-
vestigation Committee. Written informed consent was ob-
tained, and all subjects received $150 for their participation.
Subjects signed a written study commitment agreement ex-
plaining the number of visits, outcome measures, and focus
on weight, percent body fat, and cardiac risk measures.
Interventions
Subjects were randomized to daily ingestion of 1000 mgof
chromium picolinate or placebo (1630 mg of dicalcium
phosphate). The 1000 mg dose was chosen because it has been
shown to be safe and effective in modifying blood sugar and
insulin levels
18,29
and used in other clinical trials.
30
Subjects
randomized to chromium picolinate were instructed to in-
gest a 500-mg capsule twice per day during the intervention
period for a total ingestion of 1000 mg per day for 6 months.
Those randomized to placebo were instructed to ingest an
815-mg capsule twice per day during the intervention period
for a total ingestion of 1630 mg of dicalcium phosphate.
Subjects were instructed to consume these capsules with
water with morning and evening meals and to continue with
their usual dietary patterns and physical activity routines for
the first 12 weeks of intervention.
A low-intensity nutrition education and weight loss pro-
gram commenced at 12 weeks up to the 24-week point in
both the intervention and control groups. This lifestyle in-
tervention was reflective of the fact that in any real-world
setting, a patient interested in weight loss would be unlikely
to rely solely on a chromium supplement. In all probability,
some effort at ‘‘dieting’’ would accompany use of the sup-
plement. The program consisted of free access to a weight
loss website (www.thewaytoeat.net) and a copy of a book on
nutrition and weight management.
31
The nutrition education
intervention was implemented at week 12 in order to assess
any differential effects between chromium alone or in con-
junction with the nutrition education intervention, and to
standardize the weight loss efforts of study participants. It
was meant to substitute for independent weight loss efforts
by the participants, and=or the basic weight loss advice pa-
tients would be likely to receive from a primary care provider.
Objectives
This trial assessed the effects of chromium picolinate
supplementation, alone and combined with nutritional ed-
ucation on weight loss in apparently healthy overweight
adults.
Outcomes
Weight, height, and blood pressure were measured at each
visit. Prior to each assessment, subjects fasted for 8 hours for
serum and bioimpedance measures. Body weight was mea-
sured to the nearest 0.5 pound using a balance-type medical
scale. Height was measured in inches with instructions for
the subject to stand on the middle of the scale with back
against the measuring bar standing straight, without shoes,
heels together. Two (2) readings of blood pressure were
taken in a seated position 10 minutes apart using an elec-
tronic sphygmomanometer. Other outcome measures in-
cluded waist–hip ratio, percent body fat, central adiposity,
serology, and urine chromium.
Waist circumference was measured around the narrowest
point between ribs and hips when viewed from the front
after exhaling. Hip circumference was measured at the point
where the buttocks extended the maximum, when viewed
from the side. Recordings were made for each site to the
nearest 1 cm using a cloth tape without compression of
skin.
32,33
Percent body fat was recorded via bioelectrical impedance.
The imperceptible electrical current was passed through
electrodes in the subject’s foot and hand to compute body
density and body-fat percentage. The primary outcome
measure was to demonstrate a decrease in body fat from
baseline in adults with BMI 25, due to sustained ingestion
of chromium picolinate. Resistance and reactance were
measured with the Bio Analogic ELG II and the percent body
292 YAZAKI ET AL.
fat was determined with the use of Health Management
System software (www.bioanalogics.com).
For bioelectrical impedance scans, subjects were instructed
to fast and refrain from exercise 8 hours before the scan.
Subjects were also instructed to refrain from drinking alcohol
24 hours before the scan. Additional instructions included
removing metallic jewelry and maintaining adequate hy-
dration the day before the scan.
Assessed for eligibility
(n=156)
Excluded (n=76)
Not meeting eligibility critieria (n=53)
~Failed phone screen
123 Eligible for clinical screening
47 Not interested or Unable to Contact
156 Completed Clinical Screening
3 Refused to participate
Lost to follow-up (n=1) Lost to follow-up (n= 3)
Enrolled
(n=80)
Visit 1A
- CT scan
- Measurements
Visit 1A
- CT scan
- Measurements
Visit 1B
39 analyzed
Visit 1B
37 analyzed
Lost to follow-up (n= 2)
Discontinued intervention (n= 2) Lost to follow-up (n= 3)
Discontinued intervention (n= 2)
Visit 2
35 analyzed
Visit 2
32 analyzed
Lost to follow-up (n= 2)
Discontinued intervention (n= 3)
Lost to follow-up (n= 4)
Visit 3
30 analyzed
Visit 3
28 analyzed
Assigned to chromium picolinate
(n=40)
Assigned to placebo
(n=40)
FIG. 1. Study flow diagram. CT, computed tomography.
CHROMIUM PICOLINATE FOR WEIGHT LOSS 293
Central adiposity was measured at baseline to determine
the area of subcutaneous versus visceral adipose tissue.
Central adiposity was measured on a 16-slice helical G
scanner at Griffin Hospital, using standard procedures.
34–36
Subjects lay supine with their arms over their heads. A CT
scan was performed at the abdominal level (between L4 and
L5 vertebrae), using a radiograph of the skeleton as a refer-
ence to establish the position of the scan to the nearest mil-
limeter. Total abdominal adipose tissue area was calculated
by delineating the surface with a graph pen and then com-
puting the adipose tissue surface using an attenuation
range of 190 to 30 Hounsfield units using sliceOmatic
image analysis software.
34
The abdominal subcutaneous
adipose tissue area was calculated by subtracting the vis-
ceral adipose tissue area from the total abdominal adipose
tissue area using previously published criteria.
36
The calcu-
lations for subcutaneous and visceral adipose tissue were
performed at Ho
ˆpital Laval Research Center, Que
´bec,
Canada.
At each visit, lipid profile, fasting plasma glucose, fasting
insulin, Lp-PLA2, and C-reactive protein (CRP) were assessed.
All screening and serum laboratory assays with the exception
of Lp-PLA2 and CRP were performed at Griffin Hospital.
Lp-PLA2 and CRP analysis were performed at diaDexus,
Inc. (www.diadexus.com). Liver and kidney function were
monitored throughout the study by serum measurements of
transaminases, blood urea nitrogen, and creatinine.
Subjects also provided a urine specimen for analysis
of chromium output to corroborate self-report of regular use
of treatment assignment. Urine chromium was collected at
Griffin Hospital and was analyzed by Quest Laboratories.
Sample size
Thesamplesizewasdeterminedtoallowforapproxima-
tely 20% attrition and noncompliance per treatment arm and
provide at least 80% power with maximum allowable type I
error of 5%. The study was specifically powered to compare
chromium to placebo and demonstrate a 5.1% decrease in
percent body fat (the primary outcome) from baseline due to
sustained (daily for 12 weeks) ingestion of 1000 mgofchro-
mium picolinate (500 mg BID) compared to placebo.
Randomization
Subjects were enrolled and randomized using balanced
allocation within gender to ensure that an equal number of
males and females were randomized to receive chromium
and placebo. (Fig. 1). Outcome assessments were made at
baseline, 12 weeks, and 24 weeks to identify the singular
effects of chromium and placebo on weight loss, as well as
the combined effects of chromium in the context of a nutri-
tion education intervention.
Blinding
Subjects and study personnel were blinded to the inter-
vention. Chromium and placebo were prepackaged and
shipped from the manufacturer to the study site. Bottles were
labeled and coded by an unblinded individual unaffiliated
with the study. Investigators thus only knew the treatment
assignment (group A or B) of the subjects without knowl-
edge of whether these contained chromium or placebo.
Statistical methods
Repeated-measures analysis of variance was used to de-
termine change in percent body weight, BMI, and serology
after intervention between the two treatment groups. Paired
ttests were also used to evaluate the change from baseline
(pretreatment) in percent body fat, weight, BMI, and se-
rology following each treatment. The combined effects of
independent variables (abdominal fat distribution and de-
mographics) and treatment assignment on these outcomes
were assessed with multivariable models using analysis of
covariance.
Analysis was performed using the SAS for Windows
version 9.1 (SAS Institute, Cary, NC) software. In all analy-
ses, a two-tailed aof less than 0.05 was considered statisti-
cally significant. Results are expressed as means standard
deviation (SD) in text and tables.
Results
Participant flow
The two treatment arms were comparable ( p>0.05) at
baseline (Table 1) for all the outcome measures (i.e., an-
thropometric measures, blood pressure, serology, and urine
chromium). The study participants in both treatment groups
were overweight or obese at baseline (intervention group
mean BMI ¼36 kg=m
2
; control group BMI ¼36.1 kg=m
2
).
Subjects randomized to chromium picolinate had compa-
rable urinary chromium to subjects receiving placebo
(p¼0.33). Of the subjects completing the trial (n¼58), 44
subjects (76%) had pill counts reflecting greater than 80%
adherence.
Adverse effects
One subject in the chromium picolinate group experienced
urticaria 35 days after initiating daily supplement intake. He
was instructed to immediately cease taking the supplement,
and the urticaria resolved within 4 days.
After 12 weeks (chromium alone) (Table 2)
Anthropometric measures. After intervention for 12
weeks, there was no change in BMI in the chromium group
as compared to the placebo group (chromium ¼0.3
0.8 kg=m
2
versus placebo ¼0.0 0.4 kg=m
2
;p¼0.07). Simi-
larly, there was no change in percent body fat as compared
to placebo (chromium ¼0.3 1.2 versus placebo ¼0.8 3.8;
p¼0.11).
Serology. No change was seen in fasting plasma glucose
(FPG) and fasting serum insulin (FSI) levels from baseline
(FPG: chromium ¼0.0 3.1 mg=dL versus placebo ¼1.2
4.3 mg=dL; p¼0.15; insulin: chromium ¼0.8 1.9 m=mL ver-
sus placebo ¼0.5 1.6m=mL; p¼0.50). Lp-PLA2 and cell
adhesion molecules (CAM) decreased nonsignificantly
in the chromium group, as compared to placebo (Lp-PLA2:
chromium ¼3.8 44.7 ng=mL versus placebo ¼6.3 44.3
ng=mL; p¼0.36; CAM: chromium ¼1.4 18.1 nmol=min=
mL vers us placebo ¼0.5 19.8 nmol=min=mL; p¼0.86). CRP
increased nonsignificantly in the chromium group, as com-
pared to placebo (chromium ¼36.4 341.0 mg=dL versus
placebo ¼15.7 202.2 mg=dL; p¼0.78).
294 YAZAKI ET AL.
Lipids. The total cholesterol=HDL ratio did not change in
the chromium group as compared to the placebo group
(chromium ¼0.0 0.3 versus placebo ¼0.0 0.2; p¼0.78).
After 24 weeks (chromium in the context
of lifestyle intervention)
Anthropometric measures. After intervention for 24
weeks, there was no change in BMI in the chromium group
as compared to the placebo group (chromium ¼0.1
0.2 kg=m
2
versus placebo ¼0.0 0.5 kg=m
2
;p¼0.81). Simi-
larly, no improvement was observed in percent body fat as
compared to placebo (chromium ¼0.2 1.0 versus placebo ¼
0.9 3.8; p¼0.13).
Serology. Fasting plasma glucose and fasting serum in-
sulin levels in the chromium group did not improve as
compared to the placebo group (FPG: chromium ¼1.0
Table 1. Baseline Values
Outcome measures Chromium picolinate (n¼40) Placebo (n¼40) p-value
Anthropometric measures
BMI (kg=m
2
) 36.0 6.7 36.1 7.6 0.98
Waist–hip ratio 0.9 0.1 0.9 0.1 0.94
Total body fat (%) 35.9 8.6 37.2 0.1 0.48
Blood pressure
Systolic (mm Hg) 132.5 16.6 137.1 17.6 0.23
Diastolic (mm Hg) 79.5 9.7 80.9 10.9 0.55
Serum measures
Fasting plasma glucose (mg=dL) 100.0 9.9 100.3 10.6 0.91
Fasting serum insulin (m=mL) 8.7 4.6 9.8 6.7 0.43
Lp-PLA2 (PLAC test) (ng=mL) 222.9 57.0 222.1 67.0 0.96
Cellular adhesion molecules (nmol=min=mL) 149.9 32.0 139.3 42.2 0.29
High-sensitivity CRP (mg=dL) 223.2 303.7 267.4 267.1 0.53
Lipid panel
Triglyceride (mg=dL) 114.4 60.1 119.7 66.4 0.71
Cholesterol (mg=dL) 196.8 35.1 191.2 35.9 0.48
HDL (mg=dL) 50.5 12.7 48.4 11.6 0.43
LDL (mg=dL) 123.6 31.0 120.4 32.5 0.65
Cholesterol=HDL ratio 4.1 1.2 4.1 1.0 0.95
Basic metabolic panel
BUN (mg=dL) 14.9 4.0 15.4 3.4 0.49
Creatinine (mg=dL) 1.0 0.2 1.0 0.1 0.63
Sodium (mEq=L) 140.4 1.4 140.2 1.5 0.59
Potassium (mEq=L) 4.1 0.3 4.2 0.3 0.22
Chloride (mEq=L) 102.4 2.4 102.0 2.0 0.45
CO
2
(mEq=L) 28.3 2.2 30.2 11.5 0.30
Calcium (mg=dL) 9.2 0.4 9.4 0.3 0.13
Anion gap 9.8 1.8 9.8 1.8 0.90
BUN=creatinine ratio 15.6 4.3 16.0 3.7 0.65
Total protein (g=dL) 7.1 1.1 7.3 0.4 0.45
Albumin (g=dL) 4.1 0.3 4.1 0.3 0.97
AST (IU=L) 22.7 4.9 24.8 5.8 0.09
ALT (IU=L) 34.410.6 35.8 12.0 0.58
Alkaline phosphate (IU=L) 74.5 16.7 76.9 19.0 0.55
Total bilirubin (mg=dL) 0.5 0.3 0.5 0.3 0.83
Globulin (g=dL) 3.2 0.3 3.1 0.3 0.91
Albumin=globulin ratio 1.7 0.4 1.3 0.2 0.37
Urinary analysis
Chromium=creatinine ratio 0.1 0.3 0.1 0.2 0.94
Urine chromium (ng=mL) 0.2 0.1 0.3 0.3 0.35
Urine creatinine (mg=dL) 138.4 65.8 149.9 59.2 0.57
CT scan
Surface of total adipose tissue at L4–L5 level (cm
2
) 586.1 179.3 598.3 175.2 0.81
Attenuation of total adipose tissue at L4–L5 level (HU) 96.6 3.9 96.2 3.6 0.75
Surface of visceral adipose tissue at L4–L5 level (cm
2
) 199.2 85.9 207.0 110.1 0.73
Attenuation of visceral adipose tissue at L4–L5 level (HU) 88.1 5.7 88.4 6.7 0.80
Surface of subcutaneous adipose tissue at L4–L5 level (cm
2
) 401.2 120.4 399.1 110.4 0.95
Attenuation of subcutaneous adipose tissue at L4-L5 level (HU) 99.4 4.3 98.6 3.9 0.49
Sagittal diameter at L4–L5 level (cm) 29.1 4.6 29.0 5.2 0.97
BMI, body–mass index; Lp-PLA2, lipoprotein-associated phospholipase A2; CRP, C-reactive protein; HDL, high-density lipoprotein;
LDL, low-density lipoprotein; BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase; CT, computed
tomography; HU, Hounsfield units.
CHROMIUM PICOLINATE FOR WEIGHT LOSS 295
4.5 mg=dL versus placebo ¼1.0 3.8 mg=dL; p¼1.00; FSI:
chromium ¼0.2 2.1 m=mL versus placebo ¼0.2 3.0
m=mL; p¼0.54). CRP and CAM decreased nonsignificantly
in the chromium group as compared to placebo (CRP: chro-
mium ¼25.0 141.6 mg=dL versus placebo ¼5.6 154.5
mg=dL; p¼0.60; CAM: chromium ¼4.0 21.6 nmol=
min=mL versus placebo ¼0.2 16.8 nmol=min=mL; p¼
0.44). Lp-PLA2 increased nonsignificantly in the chromium
group as compared to placebo (chromium ¼7.9 57.8 ng=mL
versus placebo ¼0.3 56.3 ng=mL; p¼0.56).
Lipids. The total cholesterol=HDL ratio did not im-
prove in the chromium group as compared to the placebo
(chromium ¼0.1 0.4 versus placebo ¼0.0 0.3; p¼0.73).
Analysis using multivariable models controlling for vis-
ceral fat distribution and demographics did not significantly
alter results.
Discussion
In this study of 80 overweight or obese adult men and
women with elevated waist circumference, chromium sup-
plementation did not improve weight, blood glucose, percent
body fat, or lipid measures. To our knowledge, this is the
first study to examine the effects of the ingestion of 1000 mg
of chromium picolinate combined with a nutrition education
intervention on weight loss.
Previous studies suggest that the primary factor for a
clinical response to chromium is insulin resistance.
25,37–39
In
Table 2. Change in Outcome Measures from Baseline Values
12 weeks 24 weeks
Outcome measures
Chromium
picolinate
(n¼35)
Placebo
(n¼32) p-value
Chromium
picolinate
(n¼30)
Placebo
(n¼28) p-value
Anthropometric measures
BMI (kg=m
2
) 0.3 0.8 0.0 0.4 0.07 0.1 0.2 0.0 0.5 0.81
Waist–hip ratio 0.0 0.0 0.0 0.0 0.18 0.0 0.0 0.0 0.0 0.16
Total body fat (%) 0.3 1.2 0.8 3.8 0.11 0.2 1.0 0.9 3.8 0.13
Blood pressure
Systolic (mm Hg) 1.3 8.3 0.5 6.3 0.30 1.5 6.2 1.2 6.7 0.07
Diastolic (mm Hg) 0.5 6.9 0.4 5.2 0.55 1.4 6.7 0.3 4.5 0.21
Serum measures
Fasting plasma glucose (mg=dL) 0.0 3.1 1.2 4.3 0.15 1.0 4.5 1.0 3.8 1.00
Fasting serum insulin (m=mL) 0.8 1.9 0.5 1.6 0.50 0.2 2.1 0.2 3.0 0.54
Lp-PLA2 (PLAC test) (ng=mL) 3.8 44.7 6.3 44.3 0.36 7.9 57.8 0.3 56.3 0.56
Cellular adhesion molecules (nmol=min=mL) 1.4 18.1 0.5 19.8 0.86 4.0 21.6 0.2 16.8 0.44
High-sensitivity CRP (mg=dL) 36.4 341.0 15.7 202.2 0.78 25.0 141.6 5.6 154.5 0.60
Lipid panel
Triglyceride (mg=dL) 0.4 21.5 3.3 18.9 0.42 5.3 25.2 5.0 23.7 0.95
Cholesterol (mg=dL) 1.6 10.7 3.4 14.8 0.53 5.6 10.7 2.7 14.0 0.31
HDL (mg=dL) 0.3 2.8 0.4 3.5 0.81 1.3 5.4 0.3 3.7 0.34
LDL (mg=dL) 1.5 10.6 1.3 12.7 0.96 3.3 10.3 0.5 11.8 0.25
Cholesterol=HDL ratio 0.0 0.3 0.0 0.2 0.93 0.1 0.4 0.0 0.3 0.73
Basic metabolic panel
BUN (mg=dL) 0.2 1.6 0.4 1.7 0.74 0.2 1.2 0.1 1.7 0.41
Creatinine (mg=dL) 0.0 0.0 0.0 0.0 0.63 0.0 0.0 0.0 0.1 0.20
Sodium (mEq=L) 0.1 1.0 0.1 0.7 0.34 0.0 1.0 0.1 0.7 0.70
Potassium (mEq=L) 0.0 0.2 0.1 0.2 0.047 0.0 0.2 0.0 0.2 0.30
Chloride (mEq=L) 0.0 0.7 0.0 1.1 1.00 0.1 0.8 0.2 1.3 0.83
CO
2
(mEq=L) 0.6 1.1 0.3 0.9 0.12 0.4 1.1 0.1 1.0 0.12
Calcium (mg=dL) 0.0 0.2 0.0 0.2 0.95 0.1 0.3 0.0 0.2 0.13
Anion gap 0.7 1.1 0.2 0.8 0.05 0.5 1.0 0.4 0.8 0.62
BUN=creatinine ratio 0.0 1.9 0.2 2.3 0.70 0.2 1.2 0.3 1.7 0.21
Total protein (g=dl) 0.3 1.1 0.1 0.2 0.24 0.0 0.2 0.0 0.2 0.81
Albumin (g=dL) 0.0 0.2 0.1 0.2 0.89 0.1 0.2 0.1 0.2 0.28
AST (IU=L) 0.8 2.6 0.1 1.0 0.04 8.7 47.8 0.2 2.5 0.27
ALT (IU=L) 1.2 4.2 0.4 2.8 0.29 10.0 49.7 1.3 4.6 0.28
Alkaline phosphate (IU=L) 1.4 4.7 0.9 3.6 0.61 3.8 10.8 1.3 4.2 0.18
Total bilirubin (mg=dL) 0.0 0.1 0.0 0.1 0.90 0.0 0.1 0.0 0.1 0.82
Globulin (g=dL) 0.1 0.2 0.1 0.2 0.34 0.1 0.2 0.1 0.2 0.33
Albumin=globulin ratio 0.1 0.1 0.1 0.1 0.81 0.1 0.2 0.1 0.1 0.31
Urinary analysis
Chromium=creatinine ratio 6.8 6.2 0.0 0.2 0.07
Urine chromium (ng=mL) 0.4 1.4 0.0 0.1 0.33
Urine creatinine (mg=dL) 2.6 13.4 12.6 37.0 0.29
BMI, body–mass index; Lp-PLA2, lipoprotein-associated phospholipase A2; CRP, C-reactive protein; HDL, high-density lipoprotein; LDL,
low-density lipoprotein; BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
296 YAZAKI ET AL.
subjects who have type 2 diabetes and who use sulfonylurea
agents, Martin
39
demonstrated that chromium picolinate
improves insulin sensitivity, glucose control, and attenu-
ates body weight and visceral fat compared with placebo.
Baseline insulin sensitivity was found to account for
nearly 40% of the variance in the clinical response to chro-
mium.
25
In contrast, in this study, the baseline FPG levels
in both the chromium and placebo groups were normal
(Table 1). Our results are consistent with a meta-analysis
finding no association between chromium and glucose or
insulin concentrations among nondiabetic subjects.
40
A 2007
trial using a lower dose of chromium picolinate (200 mg) in
nondiabetic women demonstrated no effect on body weight,
composition, or iron status.
41
In 1995, a study conducted
using 400 mg of chromium picolinate had no effects in
reducing body fat percentage.
42
It is unknown whether
chromium supplementation modifies energy intake or ex-
penditure.
39
Other studies have shown modest weight loss with chro-
mium supplementation. A meta-analysis conducted on 10
randomized controlled trials (RCTs) showed that the ob-
served effect with chromium picolinate was a small reduc-
tion of 1.1–1.2 kg (0.08–0.2 kg =week) compared with placebo
in overweight and obese subjects.
16
An RCT in 42 overweight
women receiving 1000 mg of chromium picolinate demon-
strated 0.5 kg weight loss over 8 weeks, while subjects re-
ceiving placebo gained 0.5 kg during this same time period,
although the difference was not statistically significant.
43
In a small randomized trial, Cefalu et al.
44
found an in-
crease in insulin sensitivity in insulin-resistant individuals
when supplemented with 1000 mg of chromium picolinate.
These results, however, have not been replicated.
45
As
exercise-related weight loss is associated with increased in-
sulin sensitivity, it is plausible that chromium supplemen-
tation can aid in this process. Our trial, however, did not
assess insulin sensitivity. In a recent trial of 60 obese subjects,
Iqbal et al. found that 500 mg of chromium picolinate did not
improve insulin sensitivity. A statistically significant increase
in acute insulin response to glucose was found, though no
effects were seen on other measures of glucose metabolism,
lipids, body weight, and inflammatory markers.
46
High-
intensity aerobic exercise is known to increase insulin
sensitivity
47
; the combination with chromium may confer
synergistic benefits. This may be the mechanism in Kaats’
finding of statistically significant reductions in weight, body
fat, and fat mass in a randomized trial of 130 subjects re-
cruited from fitness and athletic clubs. All subjects (chro-
mium and placebo arms) lost weight during the intervention,
though the subjects in the chromium groups demonstrated
greater weight loss and improvement in body composition
than those on placebo.
48
The nutrition education intervention incorporated after
12 weeks did not demonstrate a significant effect on any
outcome measure. This may be due to the passive nature
of the intervention without rigorous follow-up and caloric
assessments. This approach was intentionally designed to
mimic real-world scenarios where patients interested in
weight loss would be likely to combine use of any supple-
ment with a lifestyle change. In general, various approaches
to ‘‘dieting’’ have been demonstrated to work in the short
term, while very few, if any, demonstrate efficacy in the long
term.
49
The nutrition program selected is healthful and bal-
anced, and provided a standardized approach for study
participants.
Our trial aimed to assess the effects of anthropometry on
chromium-mediated weight loss. We found no variation by
visceral fat distribution nor changes in BMI, and percent
body fat. Variable results in prior studies may have been due
to obesity characterized by differential fat distribution.
Obesity, in general, is associated with insulin resistance, al-
though insulin sensitivity varies significantly in nonobese
persons due to body fat distribution.
26
Persons with more
peripheral fat distribution are more insulin sensitive than
those who have body fat primarily distributed centrally in
the chest and abdomen. Furthermore, abdominal fat tends to
be more lipolytic than subcutaneous fat and not as sensitive
to the counterlipolytic effect of insulin.
26
We hypothesized that chromium might be most support-
ive of weight loss when excess weight was centrally dis-
tributed, and thus most associated with insulin resistance.
We thus recorded baseline measures of central adiposity
using CT. No association was found, however, between
variation in central fat volume and response to chromium
supplementation. Other researchers have found intriguing
results with chromium on central adiposity. In 37 subjects
with type 2 diabetes, Martin et al. demonstrated that sup-
plementation of 1000 mg chromium picolinate added to sul-
fonylurea use significantly attenuated body weight gain and
visceral fat accumulation compared with subjects receiving
sulfonylurea alone.
39
Perhaps chromium supplementation
alone does not confer specific benefits on obesity, though it
may potentiate the action of other agents that increase ab-
solute insulin levels or enhance insulin sensitivity. The
sample size of this pilot trial limited the opportunity for
subgroup analysis, and thus type II error is a possibility.
A limitation of this trial is a relatively small sample that
was largely homogeneous in demographics and socioeco-
nomic status. Furthermore, chromium viability was not as-
sessed; it may be possible that samples degraded in potency
over time, especially since urine chromium values were
not significantly different between intervention and con-
trol subjects. We did not track intake of other sources of
chromium—multivitamins and fortified foods—which may
result in differential intakes among subjects.
Conclusions
In conclusion, chromium picolinate did not affect weight
loss in the apparently healthy overweight adults enrolled in
this trial. Variable efficacy of chromium was not seen with
variation in baseline levels of abdominal adiposity. Our
findings as consistent with other recent studies examining the
relationship between chromium supplementation and weight
loss,
16,41–43
and reduce enthusiasm for the use of chromium
as a nutritional supplement for controlling weight. Benefit
of chromium supplementation in subgroups of overweight
patients, such as those with demonstrable insulin resistance
and those on intense exercise regimens, remains a possibility
warranting further research.
Acknowledgments
Funding for and products used in this study were pro-
vided by Nutrition 21, Inc.
CHROMIUM PICOLINATE FOR WEIGHT LOSS 297
Disclosure Statement
No competing financial interests exist.
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Address correspondence to:
David L. Katz, M.D., M.P.H.
Yale-Griffin Prevention Research Center
130 Division Street, 2nd Floor
Derby, CT 06418
E-mail: david.katz@yale.edu
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... Chromium can perform functions in its trivalent (Cr (III)) or hexavalent (CR (V) states. In its hexavalent state, it facilitates agents that improve insulin levels and sensitivity aiding patients with diabetes (Cr VI can serve as a cofactor to insulin) [36]. Chromium can bind directly to DNA to form DNA complexes which are stable and cause breakage in DNA strands. ...
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1. Abdominal obesity is associated with numerous metabolic complications. Deep abdominal adipose tissue is critical in the association between the level of abdominal obesity and cardiovascular risk factors. 2. Adipose tissue localization was assessed by computed axial tomography (CAT), and its association with body density and anthropometric measurements was investigated in a sample of fifty-one obese women (percentage body fat 45·9 (SD 5·6)) aged 35·7 (SD 5·5) years. The CAT scans were performed at three levels: lower chest, abdomen and mid-thigh. 3. The total adipose tissue volume computed from these three scans was highly correlated with body fat mass ( r 0·94, P < 0·001). The proportion of deep abdominal fat as measured by the ratio of deep: total adipose tissue areas at the abdominal level was not significantly correlated with body fat mass, but it was moderately associated with the ratio of waist: hip circumferences (WHR) ( r 0·49, P < 0·001). The absolute amount of deep abdominal fat was, however, significantly correlated with body fat mass ( r 0·72, P < 0·001). 4. The subscapular ( r 0·38) and the abdominal ( r 0·38) skinfolds were the only two skinfolds that were significantly associated with the proportion of deep abdominal fat ( P < 0·01). These skinfolds were also those which showed the highest correlation with the absolute amount of deep abdominal fat ( r 0·65, P < 0·001, for both skinfolds). 5. A three-site CAT-scan procedure can be used for the estimation of body fat mass in premenopausal obese women. 6. In these obese women, there was no significant association between total adiposity and the proportion of deep adipose tissue at the abdominal level. 7. In premenopausal obese women, the absolute amount of deep abdominal fat can be predicted from anthropometric measurements with more accuracy than the relative amount of deep abdominal fat.
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The adipose tissue volumes of 12 women were determined by computed tomography (CT). Body weight ranged from 46 to 129 kg. Nine or twenty-two transsectional scans were examined with respect to the adipose tissue area. The total adipose tissue volume (AC(CT22) or AT(CT9)) was calculated by assuming linear changes in the adipose tissue area between adjacent scans. Body fat (BF) was also calculated from total body potassium (BF(40K)), from total body water (BF(THO)), and from both these determinations (BF(40K + THO)). Body mass index (BMI) was calculated by dividing body weight (BW) by height2 (H2). AT(CT22), AT(CT9), and BF(K) were more closely related to BW and BMI than were BF(THO) and BF(40K + THO). When AT(CT) was used as a standard, the optimal index of adiposity based on BW and H was in the range BW/H0.8 to BW/H1.2. From the CT and 40K measurements it was possible to deduce that the potassium content is 62 mmol/kg fat free mass and 73-75 mmol/kg lean body mass. The error of AT(CT9) was 0.6%, while that of BF(40K) was at least three to four times larger. It is concluded that the CT-based AT determination is the most reproducible method so far available. The technique might turn out to be of great value in human energy balance experiments.
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Background: Body-mass index (the weight in kilograms divided by the square of the height in meters) is known to be associated with overall mortality. We investigated the effects of age, race, sex, smoking status, and history of disease on the relation between body-mass index and mortality. Methods: In a prospective study of more than 1 million adults in the United States (457,785 men and 588,369 women), 201,622 deaths occurred during 14 years of follow-up. We examined the relation between body-mass index and the risk of death from all causes in four subgroups categorized according to smoking status and history of disease. In healthy people who had never smoked, we further examined whether the relation varied according to race, cause of death, or age. The relative risk was used to assess the relation between mortality and body-mass index. Results: The association between body-mass index and the risk of death was substantially modified by smoking status and the presence of disease. In healthy people who had never smoked, the nadir of the curve for body-mass index and mortality was found at a body-mass index of 23.5 to 24.9 in men and 22.0 to 23.4 in women. Among subjects with the highest body-mass indexes, white men and women had a relative risk of death of 2.58 and 2.00, respectively, as compared with those with a body-mass index of 23.5 to 24.9. Black men and women with the highest body-mass indexes had much lower risks of death (1.35 and 1.21), which did not differ significantly from 1.00. A high body-mass index was most predictive of death from cardiovascular disease, especially in men (relative risk, 2.90; 95 percent confidence interval, 2.37 to 3.56). Heavier men and women in all age groups had an increased risk of death. Conclusions: The risk of death from all causes, cardiovascular disease, cancer or others disease increases throughout the range of moderate and severe overweight for both men and women in all age groups. The risk associated with a high body-mass index is greater for whites than for blacks. (N Engl J Med 341:1097–1105, 1999)
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A previous study using a randomized, double-masked, placebo-controlled design found that supplementation with a minimum of 200 μ;g of chromium (in the form of chromium picolinate [CrP]) per day can lead to significant improvement in body composition (as measured by underwater testing using the displacement method). The present study used a similar design in which 122 subjects were randomized to receive either CrP 400 μ;g (n = 62) or placebo (n = 60). To control caloric intake and expenditure (which was not done in the first study), participants were required to monitor and maintain a log of their daily physical activity and caloric intake. Dual energy x-ray absorptiometry measurements were taken before and after the 90-day period. Analysis of the prestudy data for the two groups revealed no significant differences in any of the initial body composition variables studied. After controlling for differences in caloric intake and expenditure, as compared with the placebo group, subjects in the active treatment group lost significantly more weight (7.79 kg vs 1.81 kg, respectively) and fat mass (7.71 kg vs 1.53 kg, respectively), and had a greater reduction in percent body fat (6.30% vs 1.20%, respectively) without any loss of fat-free mass. A more conservative analysis of covariance revealed similar and statistically significant reductions in percent body fat and fat mass without any loss of fat-free mass. It was concluded that this study replicated earlier findings that supplementation with CrP can lead to significant improvements in body composition.
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Objective: The aim of the present study was to examine whether the association of waist girth to visceral adipose tissue (AT) accumulation was altered by weight loss in abdominally obese men. Research Methods and Procedures: We studied 45 dyslipidemic abdominally obese men (45.4 ± 6.2 years of age; body mass index [BMI], 31.3 ± 3.0 kg/m2; waist circumference, 103.4 ± 7.6 cm; total cholesterol, <6.72 mM; triglycerides, ≥1.7 mM but ≤5.65 mM; high density lipoprotein cholesterol, ≤1.2 mM). Each of them followed nutritional recommendations combined with a prescription of gemfibrozil (1200 mg/d) or a placebo for 1 year. After 6 months, a training exercise program was added at a frequency of four sessions of 60 minutes per week at 50% of maximal oxygen uptake. Results: In response to the 1-year intervention program, men showed significant reductions in body weight, BMI, waist circumference, and in the partial volume of visceral and abdominal subcutaneous AT measured from two abdominal computed tomography scans performed at lumbar vertebra (L)2 to L3 and L4 to L5 levels. No change in waist-to-hip ratio was observed. Changes in visceral AT were strongly correlated with changes in body weight, BMI, and waist circumference (0.83 < r < 0.85; p < 0.001). However, a weak association was noted between waist-to-hip ratio and changes in visceral AT (r = 0.40; p < 0.05). There was no change in slopes or in intercepts before and after treatment in the relationships between volume or area of abdominal AT and anthropometric markers. Discussion: Despite a greater level of the partial volume of subcutaneous AT than of the partial volume of visceral AT at baseline (p < 0.001), the greater relative reduction in the visceral AT volume in comparison with the subcutaneous AT volume suggested a preferential mobilization of visceral AT with weight loss in these abdominally obese men. The close relationship between changes in the partial volume of visceral AT and changes in cross-sectional areas of visceral AT measured at L2 to L3 (r = 0.94; p < 0.001) or L4 to L5 (r = 0.88; p < 0.001) suggests that a single computed tomography scan performed at L2 to L3 or L4 to L5 could predict changes in the partial volume of visceral AT secondary to weight loss.
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This study assessed the effect of chromium (Cr) supplementation on insulin sensitivity and body composition in subjects at high risk for Type 2 diabetes because of family history and obesity. Twenty-nine subjects (14 men, 15 women) were evaluated in a double-blind, randomized, placebo-controlled trial using chromium picolinate (CrPic) (1,000 μg/day), or placebo for 8 months of study. Clinical and metabolic evaluations consisted of insulin sensitivity (SI) and glucose effectiveness (Sg); measurement of glucose tolerance and insulin response to an oral glucose tolerance test (75 g OGTT); and 24-hour glucose and insulin profiles. Anthropometric measures and magnetic resonance imaging (MRI) assessed abdominal fat distribution. Fasting plasma glucose and insulin levels and measures of glycemia (glycated hemoglobin and fructosamine) were also assessed. The CrPic group showed a significant increase in insulin sensitivity at midpoint (P < .05) and end of study (P < .005) compared with controls, which had no significant changes. No change in Sg was seen in either group. There was no effect of CrPic on body weight, abdominal fat distribution, or body mass index. However, CrPic significantly improved insulin sensitivity in these obese subjects with a family history of Type 2 diabetes. Improvement in insulin sensitivity without a change in body fat distribution suggests that Cr may alter insulin sensitivity independent of a change in weight or body fat percentage, thereby implying a direct effect on muscle insulin action. Definitive double-blinded, placebo-controlled trials are currently being conducted to confirm this observation in Type 2 diabetic subjects and evaluate the effects of Cr supplementation on insulin action and glycemic control. J. Trace Elem. Exp. Med. 12:71–83, 1999. © 1999 Wiley-Liss, Inc.