Effects of Whey Protein Isolate on Body Composition, Lipids, Insulin and Glucose in Overweight and Obese Individuals

Abstract

The health benefits currently associated with increased dairy intake may be attributable to the whey component of dairy proteins. The present study evaluated the effects of whey protein supplementation on body composition, lipids, insulin and glucose in comparison to casein and glucose (control) supplementation in overweight/obese individuals for 12 weeks. The subjects were randomised to whey protein, casein or glucose supplementation for 12 weeks according to a parallel design. Fasting blood samples and dual-energy X-ray absorptiometry measurements were taken. Seventy men and women with a mean age of 48.4 (SEM 0.86) years and a mean BMI of 31.3 (SEM 0.8) kg/m2 completed the study. Subjects supplemented with whey protein had no significant change in body composition or serum glucose at 12 weeks compared with the control or casein group. Fasting TAG levels were significantly lowered in the whey group compared with the control group at 6 weeks (P = 0.025) and 12 weeks (P = 0.035). There was a significant decrease in total cholesterol and LDL cholesterol at week 12 in the whey group compared with the casein (P = 0.026 and 0.045, respectively) and control groups (P < 0.001 and 0.003, respectively). Fasting insulin levels and homeostasis model assessment of insulin resistance scores were also significantly decreased in the whey group compared with the control group (P = 0.049 and P = 0.034, respectively). The present study demonstrated that supplementation with whey proteins improves fasting lipids and insulin levels in overweight and obese individuals.

Full text

Effects of whey protein isolate on body composition, lipids, insulin and glucose
in overweight and obese individ uals
Sebely Pal*, Vanessa Ellis and Satvinder Dhaliwal
School of Public Health, Curtin Health Innovation Research Institute, ATN Centre for Metabolic Fitness, Curtin University
of Technology, GPO Box U1987, Perth, WA 6845, Australia
(Received 18 November 2009 – Revised 23 February 2010 – Accepted 24 February 2010 – First published online 9 April 2010)
The health benefits currently associated with increased dairy intake may be attributable to the whey component of dairy proteins. The present study
evaluated the effects of whey protein supplementation on body composition, lipids, insulin and glucose in comparison to casein and glucose
(control) supplementation in overweight/obese individuals for 12 weeks. The subjects were randomised to whey protein, casein or glucose
supplementation for 12 weeks according to a parallel design. Fasting blood samples and dual-energy X-ray absorptiometry measurements were
taken. Seventy men and women with a mean age of 48·4 (
SEM 0·86) years and a mean BMI of 31·3 (SEM 0·8) kg/m
2
completed the study. Subjects
supplemented with whey protein had no significant change in body composition or serum glucose at 12 weeks compared with the control or casein
group. Fasting TAG levels were significantly lowered in the whey group compared with the control group at 6 weeks (P¼ 0·025) and 12 weeks
(P¼ 0·035). There was a significant decrease in total cholesterol and LDL cholesterol at week 12 in the whey group compared with the
casein (P¼ 0·026 and 0·045, respectively) and control groups (P, 0·001 and 0·003, respectively). Fasting insulin levels and homeostasis model
assessment of insulin resistance scores were also significantly decreased in the whey group compared with the control group (P¼ 0·049 and
P¼ 0·034, respectively). The present study demonstrated that supplementation with whey proteins improves fasting lipids and insulin levels in
overweight and obese individuals.
Metabolic syndrome: Whey protein: Lipid: Obesity: Cholesterol: Insulin: Glucose
It is now estimated that over 20 % of adults in many Western
countries have the metabolic syndrome with numbers continu-
ing to increase
(1,2)
. The metabolic syndrome is classified as a
combination of risk factors such as obesity, atherogenic
dyslipidaemia, hypertension, glucose intolerance and insulin
resistance, which significantly increases the risk of developing
CVD and type 2 diabetes mellitus
(3,4)
. Many studies, including
the National Health and Nutrition Examination Survey
(1999–2004), and the Coronary Artery Risk Development In
Young Adults study have suggested that higher dairy con-
sumption reduces the risk of obesity
(5,6)
. It has been proposed
that specific components of dairy, such as Ca, other minerals,
casein or whey proteins
(7)
, may have beneficial effects on
metabolic risk factors.
Milk contains two major protein groups: caseins and whey
proteins. Caseins account for almost 80 % and whey accounts
for 20 % of total protein in bovine milk
(8)
. Casein and whey
are both heterogeneous groups of proteins containing all the
common amino acids, and are especially rich in the essential
ones. Whey proteins contain globular proteins that can be
isolated from whey, a by-product of cheese manufactured
from cows’ milk
(8)
.
A study by Bowen et al.
(9)
suggested that the whey
and casein protein components of dairy appear to be more
important for weight loss than Ca in overweight adults due
to their high concentrations of branched-chain amino acids.
However, there is little evidence of beneficial effects of
casein beyond it being a good quality source of protein and
having a possible hypotensive effect
(10 – 12)
. In a separate
article, we have shown that both whey and casein proteins
consumed over 12 weeks significantly reduced diastolic and
systolic blood pressure from baseline in overweight individ-
uals; however, whey protein consumption also significantly
reduced arterial stiffness
(12)
. Some studies demonstrate that
dairy whey proteins have a better effect on appetite control
than other protein sources such as egg and casein
(13 – 15)
.
In addition, convincing evidence indicates that dairy whey
proteins and their bioactive components such as lactalbumin,
angiotensin-converting enzyme inhibitor and branched-chain
amino acids may have an insulinotrophic effect
(16 – 20)
, hypo-
triacylglycerolaemic effect
(21)
, muscle-sparing effect
(22 – 24)
and cholesterol-lowering effect
(25)
. However, most of these
studies using whey proteins have been conducted in healthy
individuals or animals, with limited studies in overweight/
obese individuals. Given the effect of whey proteins on appe-
tite control, muscle sparing and lipid metabolism demons-
trated previously in healthy adults, our hypothesis was that
whey protein consumption would also have a beneficial
* Corresponding author: Dr Sebely Pal, fax þ 61 8 9266 2258, email s.pal@curtin.edu.au
Abbreviation: TC, total cholesterol.
British Journal of Nutrition (2010), 104, 716–723 doi:10.1017/S0007114510000991
q The Authors 2010
British Journal of Nutrition

effect on metabolic risk factors in overweight and obese
individuals, a population highly susceptible to the metabolic
syndrome. Therefore, the aim of the present study was to
compare the effect of whey and casein consumption on
lipids, insulin, glucose and body composition in overweight/
obese individuals.
Methods and procedure
Subjects
Overweight and obese individuals between the ages of 18–65
years with a BMI between 25 and 40 kg/m
2
were recruited
through advertisements in the local newspapers and television
exposure. Of the 380 who responded, 97 were eligible to
participate and 89 commenced the study. The suitability
assessments were conducted via telephone and online followed
by screenings in person. Exclusion criteria included taking
regular medications (such as lipid-lowering agents and hyper-
tensives), kidney and liver diseases, cancer within the last
5 years, smoking, pregnancy or lactation, over two standard
alcoholic drinks per day, type 1 or type 2 diabetes, liver or
kidney diseases, and cardiovascular events in the last 6 months.
Study design and methodology
This was a randomised, parallel design study conducted over a
12-week period where subjects were randomised to one of the
three groups, whey protein group, casein protein group or the
control group (glucose), using a simple randomisation table.
The subjects had no knowledge of the supplement type as
they were all closely matched for taste and appearance.
After randomisation, subjects were asked to consume one of
the following supplement sachets mixed with 250 ml water
twice a day for 12 weeks: whey protein isolate, sodium case-
inate (both containing 27 g protein) or glucose control (27 g
glucose; MG Nutritionals, Brunswick, Vic, Australia). The
protein supplement compositions are given in Table 1.
The kJ content of all supplement sachets was equal to
525 kJ per sachet. Subjects were instructed to take one
sachet within 30 min before breakfast and one within 30 min
before their evening meal. To monitor compliance, subjects
were asked to record their consumption of the supplements
by completing tailored calendar tick boxes and bringing
their empty sachets to their 6- and 12-week visits.
All subjects were asked to maintain their usual dietary intake
and physical activity levels during the study. Weighed food
records were completed by subjects before commencement of
the study to gain baseline intake data, and every 2 weeks of
the study (weeks 2, 4, 6, 8 and 12) on two weekdays and one
weekend day to assess compliance. To maintain isoenergetic
diets, subjects were given individual instruction by the study
dietitian to reduce their usual dietary intake by about 1050 kJ
per day (equal to two sachets of supplements) which they
recorded on the weighed food diary. This was monitored, and
subjects were contacted if they were under- or over-compensat-
ing. All subjects were instructed to maintain dairy intake at
one serve per day for 4 weeks leading up to and during the
study period, to limit alcohol to two or less standard drinks for
men and one or less standard drinks for women, and to not
take any multivitamins or herbal supplements during the study
period. All other aspects of their dietary intake were to remain
unchanged. Energy and nutrient compositions were calculated
using FoodWorks 2007 (Xyris Software, Highgate Hill, QLD,
Australia) based on the Australian food composition tables.
Assessments
Subjects were assessed at baseline, 6 and 12 weeks. Body
weight (UM-018 Digital Scales; Tanita Corporation, Tokyo,
Japan) was recorded in light clothing without shoes. Height
was measured to the nearest 0·1 cm using a stadiometer
(26SM 200 cm SECA, Hamburg, Germany) without shoes.
Waist circumference was measured three times in the standing
position at the narrowest area between the lateral lower rib and
the iliac crest, and the measures were averaged. Total body
fat, lean mass, android fat (fat around the abdomen and
trunk) and gynoid fat (fat around the hips, thighs and buttocks)
as well as percentage fat were assessed by whole body dual-
energy X-ray absorptiometry (Lunar Prodigy; Lunar, Madison
WI, USA) at baseline and at 12 weeks.
Measurement of plasma lipids, insulin and homeostasis model
assessment
An 8·5 ml fasting blood sample was taken via venepuncture
from subjects in the fasting state, at baseline, 6 and 12
weeks, to measure circulating insulin, glucose and lipids
(TAG, NEFA, HDL, LDL and apo B). Serum was isolated
by centrifugation at 3000 rpm at 4 8C for 10 min, and was
stored at 2 80 8C until the end of the study. Serum TAG
and total cholesterol (TC) were measured using enzymatic
colorimetric kits (TRACE Scientific Limited, Noble Park,
Vic, Australia). Serum HDL cholesterol was determined
after precipitation of apo B-containing lipoproteins with
phosphotungstic acid and MgCl
2
; HDL cholesterol present in
the supernatant was determined by enzymatic colorimetry
(TRACE Scientific Limited). Serum LDL cholesterol was
determined using a modified version of the Friedewald
equation
(26)
. NEFA were determined using WAKO NEFA C
kit. Apo B was analysed using an ELISA kit obtained from
Mabtech AB (Nacka Strand, Sweden). Plasma glucose levels
were measured using the Randox glucose GOD – PAP kit
(Antrim, UK), and plasma insulin was measured using an
ELISA kit (Dako Diagnostic, Kyoto, Japan). The homoeo-
stasis model of assessment index 2 was used to assess insulin
resistance (homeostasis model assessment of insulin resistance)
from fasting glucose and insulin concentrations
(27)
.
Table 1. Protein supplement typical composition in two sachets per
day (60 g)
Component (g) Whey protein isolate Sodium caseinate
Protein (total N £ 6·38) 54·00 54·30
Fat 0·30 0·72
Carbohydrate – lactose 0·30 0·12
Moisture 1·32 0·78
Ash 2·20 2·20
Sweetener (Sucralose) 0·04 0·04
Flavouring 1·80 1·80
Ca 0·09 0·06
P 0·18 0·46
Effect of whey on lipids, insulin and glucose 717
British Journal of Nutrition

Statistical analysis
All subjects who completed the study were included in
the data analysis. Statistical analysis was conducted using
SPSS 17 for Windows (SPSS, Inc., Chicago, IL, USA).
Data are expressed as mean values with their standard
errors, and were assessed for normality. Comparison of
baseline characteristics between each group was undertaken
by one-way ANOVA. Differences within groups were deter-
mined using a two-sided paired t test. Using one-way analysis
of covariance with the baseline data as the covariate,
differences between groups were determined at week 6 to
assess immediate effects of intervention and at week 12
to assess longer term effects of supplementation. Statistical
differences were analysed further by post hoc analysis
using the least square differences method. Percentage change
between groups was calculated based on raw values
of group means. Statistical significance was considered
at P, 0·05.
The present study was conducted according to the guide-
lines laid down in the Declaration of Helsinki, and all
procedures involving human subjects/patients were approved
by the Curtin University Human Research Ethics Committee
(Approval Number HR 149/2007). Written informed consent
was obtained from all subjects.
This clinical trial has been registered with the Australian
New Zealand Clinical Trials Registry. The registration
number is ACTRN12609000175279, and trial Web address
is http://www.ANZCTR.org.au/ACTRN12609000175279.aspx
Results
Eighty-nine individuals were randomly assigned to either a
control, casein or whey protein supplement for 12 weeks.
Nineteen subjects withdrew from the study within 4 weeks
after randomisation due to non-compliance for various reasons
as shown in Fig. 1. Seventy subjects completed the 12-week
Response to advertisement
n
380
Subjects screened
n
161
Eligible for participation
n
97
Randomisation
n
89
Week 0
Glucose supplement (control)
n
30
Week 0
Casein supplement
n
29
Week 0
Whey supplement
n
30
Week 12
Completed
Control
n
25
Week 12
Completed
Casein
n
20
Week 12
Completed
Whey
n
25
Withdrawal before randomisation
n
9 due to work commitments
or personal reasons
Withdrawals
after commencement
(
n
5)
Personal reasons
unrelated to diet (
n
4)
Struggled with
supplement or
protocol (
n
1)
Withdrawals
after commencement
(
n
9)
Lost to follow up (
n
1)
Personal reasons
unrelated to diet (
n
4)
Travel
commitments (
n
2)
Struggled with
supplement or
protocol (
n
2)
Withdrawals
after commencement
(
n
5)
Lost to follow up (
n
3)
Personal reasons
unrelated to diet (
n
2)
Fig. 1. Details of subject recruitment and withdrawal.
S. Pal et al.718
British Journal of Nutrition

study (control group: n 25, twenty-two women and three men;
casein group: n 20, seventeen women and three men; whey
protein group: n 25, twenty-one women and four men).
Subject characteristics in the three treatment arms at baseline
were not significantly different.
The self-reported composition of the study diets consumed
during the 3-month study period is presented in Table 2. There
were no significant differences in total energy, total fat,
saturated fat, monounsaturated fat, polyunsaturated fat, Ca
and fibre between control, casein and whey protein groups
(Table 2). The contribution of carbohydrate to total energy
intake was lower in the casein group (P, 0·001) and
whey group (P, 0·001) compared with the control group.
The contribution of protein to total energy intake was higher
in subjects in the casein group (P, 0·001) and whey group
(P, 0·001) compared with the control group.
Changes in body composition (Table 3) were assessed
by body weight, waist and hip circumference measurements
and body composition scans by dual-energy X-ray absorp-
tiometry. There was no overall effect of supplements on
body weight, BMI, waist, waist:hip ratio, total body fat,
android fat, gynoid fat and lean body mass between groups
at 6 or 12 weeks, with no difference within groups.
Table 4 shows the mean fasting levels of all blood measure-
ments from each intervention group at the three visits, and
summarises the significant within-group and between-group
differences. Fasting TAG concentrations decreased by 13 %
at week 6 (P¼ 0·008) and week 12 (P¼ 0·003) compared
with baseline in the whey protein group. Fasting TAG levels
were lowered by 22 % in the whey protein group compared
with the control group at 6 weeks (P¼ 0·025) and by 22 %
at 12 weeks (P¼ 0·035).
TC levels in plasma (Table 4) were decreased by 7 % at
week 12 in the whey group compared with baseline (P, 0·001).
There was a lowering in TC at week 6 in the whey protein
group compared with the control group (P¼ 0·044). There
was a decrease in TC by 9 % at week 12 in the whey protein
group compared with the casein group (P¼ 0·026) and by 11 %
compared with the control group (P, 0·001). Plasma LDL
was reduced by 7 % at week 12 in the whey group compared
with baseline (P¼ 0·007). There was an attenuation in plasma
LDL levels at week 12 in the whey protein group compared
with the casein (P¼ 0·045) and control groups (P¼ 0·003).
There was an 11 % reduction in plasma insulin levels
(Fig. 2(a)) in the whey protein group at 12 weeks (41·71
(
SEM 3·80) pmol/l) compared with baseline (46·96 (SEM 3·76)
pmol/l; P¼ 0·012). There was also a lowering in fasting insulin
levels in the whey protein group (41·71 (
SEM 3·80) pmol/l) com-
pared with the control group (54·77 (
SEM 5·185); P¼ 0·049)
at 12 weeks. There was a decrease in homeostasis model
Table 2. Nutritional data recorded in 3 d food diaries
(Mean values with their standard errors, n 70)
Baseline Week 6 Week 12
Mean
SEM Mean SEM Mean SEM
Total EI (kJ/d)
Control 7535·9 373·9 7385·0 1197·8 7244·9 337·9
Casein 7072·6 212·4 6564·7 263·3 6721·9 235·8
Whey 7770·4 415·5 7353·2 447·0 7507·0 385·1
Carbohydrate (% of EI)
Control 45·7 1·3 50·5*
a
0·9 51·5†
a
1·1
Casein 41·6 1·5 37·2*
b
1·2 35·3†
b
1·3
Whey 43·7 1·1 36·5*
b
0·9 34·9†
b
1·3
Protein intake (% of EI)
Control 18·3 0·7 16·4*
a
0·6 15·8†
a
0·7
Casein 20·5 0·8 33·4*
b
1·1 32·9†
b
0·8
Whey 19·9 0·8 31·3*
b
0·9 31·9†
b
0·8
Fat intake (% of EI)
Control 33·0 1·0 31·0 0·9 30·1 0·9
Casein 34·9 1·1 30·4 1·1 29·3 1·0
Whey 33·7 1·1 31·4 1·0 29·7 0·9
SFA (% of total fat)
Control 42·0 2·1 38·6 1·2 41·4 1·0
Casein 38·2 1·8 41·0 1·5 40·0 1·0
Whey 42·4 1·3 41·1 1·3 41·3 1·1
MUFA (% of total fat)
Control 41·1 0·7 41·2 0·8 40·0 0·5
Casein 42·0 1·1 40·3 1·0 41·6 0·9
Whey 40·0 0·8 41·3 1·0 41·3 0·8
PUFA (% of total fat)
Control 16·9 0·8 18·5 0·9 18·5 1·1
Casein 19·1 1·6 18·4 1·3 18·3 0·8
Whey 16·4 0·8 17·6 0·7 16·8 0·8
EI, energy intake.
a,b
Mean values with unlike superscript letters were significantly different between groups at 6 and
12 weeks (P, 0·05).
* Mean values were significantly different within group (time 0 v. time 6 weeks, P, 0·05).
† Mean values were significantly different within group (time 0 v. time 12 weeks, P, 0·05).
Effect of whey on lipids, insulin and glucose 719
British Journal of Nutrition

assessment of insulin resistance scores at 12 weeks in the
whey protein group (0·82 (
SEM 0·08)) compared with baseline
(0·91 (
SEM 0·07); P¼ 0·046) (Fig. 2(b)). There was a decrease
in homeostasis model assessment of insulin resistance scores
in the whey treatment group (0·82 (
SEM 0·08)) compared with
the control group at 12 weeks (1·01 (
SEM 0·10); P¼ 0·034).
Discussion
Previous studies have demonstrated the effect of whey pro-
teins on appetite control, muscle sparing and lipid metabolism
in healthy adults, but limited data are available for the effect
of whey protein consumption on metabolic risk factors in
overweight and obese individuals. In the present study, supple-
mentation with whey protein for 12 weeks decreased TC and
LDL cholesterol levels compared with the supplementation
with control and casein. Whey protein also decreased
plasma TAG, insulin and homeostasis model assessment of
insulin resistance scores compared with the control. There
was no effect of casein supplementation on any metabolic
risk parameter compared with control supplementation.
Overall, the present study demonstrated that whey protein
supplementation can significantly improve metabolic risk
factors associated with chronic diseases in overweight and
obese individuals.
Supplementation with whey protein significantly lowered
plasma TC and LDL cholesterol after 12 weeks compared
with the supplementation with casein and control. Interestingly,
a decrease in LDL cholesterol levels with whey protein was
observed without changes in apo B levels, indicating a change
in LDL particle size rather than in particle number. Lipid-
lowering agents such as statins, fibric acid and nicotinic acid
have been shown to lower LDL levels from 5 to 55 %, resulting
in a CHD risk reduction of 25–45 % with 5 years of treatment
in randomised, placebo-controlled clinical trials
(28)
. A meta-
analysis by Baigent et al.
(29)
found that over 5 years, every
mmol/l reduction in LDL cholesterol by statin therapy resulted
in a 12 % reduction in all-cause mortality and a 19 % reduction
in coronary mortality. Similarly, a 20 –24 % reduction in TAG
levels has been shown to reduce the progression of CHD
(30)
.
Therefore, a reduction in serum TC by 11 %, in LDL cholesterol
by 9·6 % and in TAG by 22 % after 12 weeks of whey
supplementation in the present study may also be clinically
significant. The effect of whey proteins on lipid levels in
the present study is consistent with earlier animal experi-
ments mostly undertaken in rats
(21,31,32)
and healthy men
(21)
.
Table 3. Body composition measurements*
(Mean values with their standard errors)
Baseline Week 6 Week 12 Change
Mean
SEM Mean SEM Mean SEM Mean SEM
Weight (kg)
Control 84·1 1·8 83·9 1·8 83·8 1·9 2 0·28 0·38
Casein 82·9 3·1 82·1 3·1 82·0 3·1 2 0·90 0·42
Whey 90·5 3·4 90·3 3·8 89·7 3·2 2 0·78 0·45
BMI (kg/m
2
)
Control 30·6 0·9 30·6 1·5 30·5 1·5 2 0·04 0·14
Casein 31·3 0·9 31·0 0·9 30·9 0·9 2 0·31 0·15
Whey 32·0 0·8 32·0 0·7 31·8 0·8 2 0·23 0·16
Waist (cm)
Control 93·7 1·5 95·1 1·7 93·7 1·6 2 0·02 0·46
Casein 92·1 2·1 93·7 2·6 91·2 2·1 2 0·93 0·52
Whey 95·9 1·7 97·6 2·0 95·5 1·9 2 0·03 0·42
Waist:hip ratio
Control 0·83 0·01 0·84 0·01 0·84 0·01 0·01 0·02
Casein 0·81 0·02 0·83 0·01 0·82 0·02 0·00 0·02
Whey 0·82 0·01 0·83 0·01 0·83 0·01 0·01 0·01
Total body fat (kg)
Control 35·4 1·1 35·1 1·1 2 0·36 0·2
Casein 35·1 2·1 34·1 2·1 2 0·90 0·35
Whey 37·6 1·9 37·6 1·8 2 0·04 0·31
Total lean (kg)
Control 44·5 1·7 44·7 1·8 0·14 0·26
Casein 43·9 1·7 43·7 1·6 2 0·26 0·21
Whey 48·3 2·3 48·6 2·4 2 0·30 0·45
Android fat (%)
Control 50·2 1·2 50·0 1·3 2 0·21 0·44
Casein 49·0 1·2 48·4 1·5 2 0·66 0·52
Whey 49·7 1·1 49·9 1·1 0·30 0·37
Gynoid fat (%)
Control 48·3 1·4 47·9 1·3 2 0·34 0·52
Casein 47·8 2·3 46·9 1·6 2 0·87 0·37
Whey 48·1 1·5 47·3 1·6 2 0·30 0·36
* There were no significant differences at baseline between diets. There were no significant differences
between groups.
S. Pal et al.720
British Journal of Nutrition

In the present study, whey protein consumption did not
change body composition. Therefore, the beneficial changes
in TC, LDL cholesterol and TAG from whey supplementation
seem to have occurred independently of changes in body
weight or fat mass. The mechanisms behind the favourable
effects on lipids may be related to the effect of whey
proteins on de novo cholesterol biogenesis in the liver
(33)
,
the inhibition of cholesterol absorption in the intestine
mediated by b-lactoglobulin
(32)
, the inhibition of the
expression of genes involved in intestinal fatty acid and
cholesterol absorption and synthesis
(34)
and/or the increase
in faecal steroid excretion
(35)
.
The differential effects on lipid metabolism between whey
and casein may be related to their specific influence on
digestion and absorption and their amino acid content
(13,36)
.
Whey proteins have been shown to have a fast rate of diges-
tion and absorption producing a rapid peak in plasma amino
acids compared with casein. Whey also has a higher
branched-chain amino acids content compared with casein.
Unlike whey, casein is a coagulating protein and exhibits a
slower rate of gastric emptying and also mediates lower post-
prandial excursions of plasma amino acid concentrations
(13,36)
.
Casein has been shown numerous times to produce higher
levels of serum cholesterol and LDL when compared with
soya proteins, and this is thought to be due to its unusually
low content of cysteine
(37,38)
.
In the present study, whey protein supplementation
decreased plasma insulin levels by 11 % at 12 weeks and
improved insulin sensitivity. Insulin-resistant rats were fed a
high-protein diet for 6 weeks, either whey or red meat protein;
the whey protein concentrate reduced plasma insulin by 40 %
and increased insulin sensitivity
(16)
. These changes were
explained by the reduction in visceral fat in the rats fed the
whey protein diet, because visceral obesity is strongly corre-
lated with insulin resistance. However, in the present study,
there were no changes in body fat to explain changes in insulin
sensitivity. Interestingly, postprandial studies have demon-
strated that whey proteins have a stimulating effect on insulin
secretion in healthy subjects
(18)
and in diabetics
(17)
. In healthy
subjects, ingestion of a mixture of leucine, isoleucine, valine,
lysine and threonine resulted in glycaemic and insulinaemic
responses similar to those resulting after whey ingestion
(20)
,
suggesting that branched-chain amino acids are the major
determinants of insulinaemia as well as lowered glycaemia.
The key mechanism is not known, although elevated concen-
trations of specific insulinogenic amino acids as well as bio-
active peptides, either originally present in whey or formed
during digestion, are possible. The short-term insulinotrophic
Table 4. Concentration of plasma lipids, lipoproteins, glucose and NEFA*
(Mean values with their standard errors)
Baseline Week 6 Week 12 Change
Mean
SEM Mean SEM Mean SEM Mean SEM
TAG (mmol/l)
Control 1·21 0·08 1·21
a
0·08 1·20
a
0·09 0·00 0·06
Casein 1·10 0·11 1·00
a,b
0·10 1·00
a,b
0·10 2 0·10 20·10
Whey 1·07 0·08 0·93†
b
0·05 0·93‡
b
0·07 2 0·15 0·04
TC (mmol/l)
Control 5·43 0·17 5·53
a
0·18 5·58
a
0·18 0·15 0·13
Casein 5·34 0·23 5·38
a,b
0·23 5·30
a
0·23 2 0·04 0·12
Whey 5·36 0·17 5·18
b
0·18 4·97‡
b
0·16 2 0·38 0·08
HDL (mmol/l)
Control 1·61 0·07 1·61 0·07 1·61 0·06 0·00 0·04
Casein 1·65 0·08 1·54 0·08 1·62 0·08 2 0·03 0·03
Whey 1·56 0·07 1·51 0·06 1·53 0·06 2 0·03 0·43
LDL (mmol/l)
Control 3·25 0·15 3·36 0·16 3·41
a
0·16 0·16 0·10
Casein 3·32 0·24 3·27 0·25 3·36
a
0·22 0·03 0·09
Whey 3·31 0·17 3·20 0·15 3·08‡
b
0·12 2 0·22 0·08
NEFA (mmol/l)
Control 0·51 0·02 0·55 0·03 0·56 0·03 0·05 0·04
Casein 0·59 0·04 0·63 0·03 0·60 0·03 0·01 0·03
Whey 0·60 0·04 0·52 0·03 0·54 0·02 2 0·05 0·03
Glucose (mmol/l)
Control 5·46 0·11 5·57 0·09 5·65 0·09 0·19 0·11
Casein 5·49 0·13 5·50 0·15 5·56 0·12 0·07 0·07
Whey 5·56 0·12 5·54 0·11 5·70 0·13 0·14 0·09
Apo B (ng/ml)
Control 220·41 23·20 250·70 29·21 30·30 13·8
Casein 253·20 18·90 285·60 22·42 32·30 14·8
Whey 207·60 15·80 223·80 18·57 16·10 7·8
TC, total cholesterol.
a,b
Mean values with unlike superscript letters were significantly different between groups at 12 weeks (P, 0·05).
* There were no significant differences at baseline between diets.
† Mean values were significantly different within group (time 0 v. time 6 weeks, P, 0·05).
‡ Mean values were significantly different within group (time 0 v. time 12 weeks, P, 0·05).
Effect of whey on lipids, insulin and glucose 721
British Journal of Nutrition

effect of whey proteins may be a valuable tool in the
management of type 2 diabetes or the metabolic syndrome.
Today, sulphonylurea agents are commonly used to stimulate
insulin secretion and to attenuate postprandial blood glucose
for the purpose of facilitating normoglycaemia in diabetic
subjects. However, further studies are required to resolve
why whey proteins can have an insulinotrophic effect in
the short term, but can decrease plasma insulin levels and
improve insulin sensitivity in the long term.
A study limitation involved the self-reporting of energy
intake by the study participants. Mean intakes of about
7000 kJ as recorded in the present study would not represent
the true energy intake of overweight or obese individuals on
an isoenergetic diet. However, it is well established that under-
reporting of energy intake in this population is preva-
lent
(39 – 41)
, and is an accepted study limitation. Despite the
underreporting, analysis of the weighed food records enabled
monitoring of any changes in energy intake and macronutrient
as well as dairy product intake.
In the present study, most subjects had a waist circum-
ference greater than that specified by the ATP III Clinical
Identification of Metabolic Syndrome
(3)
. In addition, most
subjects already had at least one or two other metabolic
syndrome risk factors or were borderline candidates. Many
in this group will eventually progress to establish the
metabolic syndrome if their obesity continues. As the
consumption of whey proteins in this group has beneficial
effects on serum lipids and insulin, regular whey protein
supplementation may, at the very least, slow down the
progression to the metabolic syndrome, CVD or diabetes,
and/or may delay the need for medications. Collectively,
whey protein has the potential to be used as an added
component in dietary plans and in functional foods aimed at
the management of chronic diseases in overweight and
obese individuals.
Acknowledgements
The present study is a Dairy Australia initiative funded by
the Dairy Service Levy and the Australian Government
(grant no. CUT11913). We thank Murray Goulburn Nutritionals
(Vic, Australia) for providing the supplements. The authors
declare that they have no competing interests. The authors’
responsibilities were as follows: V. E. coordinated the trial,
data collection and input for the manuscript. S. P. conceived
and designed the study, wrote the manuscript, and supervised
the study and the statistical analysis; S. D. provided support
with the statistical analysis and input for the manuscript.
All authors have read and approved the final manuscript.
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