This study will recruit 60 participants that are overweight/obese people suffering from
metabolic syndrome. The participants will be asked to come to the Clinical Nutrition
Research Centre (CNRC) for a screening session (1st visit) and given plenty of time to
read this information sheet and the opportunity to ask questions. Once the participants
are fully informed regarding the study and all their questions have been satisfactorily
answered, the participants will be given a consent form to complete and sign in the
presence of the researcher. Following this, in order to gauge their suitability for
taking part in the study, an assessment will be carried out. This assessment needs to be
carried out in a fasted state and participants would therefore have to come one morning
following an overnight fast. The screening will include anthropometric measurements,
blood pressure measurement and blood sampling. Anthropometric measurements taken will be
height, weight, waist circumference and hip circumference. Body composition will be
measured using an electrical impedance analyser (BIA). Blood pressure will be measured
using an automatic blood pressure monitor. The participants will also undergo a blood
sampling from their vein (6 mL or approximately 1.5 teaspoons) to be tested for thyroid
function, glucose and lipid profile. Pre-menopausal females will also undergo a urine
pregnancy test to exclude pregnancy prior to participation at study entry. The
participants who have been accepted into the study will be randomly assigned to one of
the 3 parallel intervention groups below (20 subjects per group) via an online randomizer
(www.randomizer.org). Randomization means assigning them to one of the three groups by
chance, like tossing a coin or rolling a dice. The 3 parallel intervention groups (Week 0
to 12) are Group 1 (CS): Cold stimulation using cooling vest x 60 min once daily over 3
months, Group 2 (BN): Browning nutraceutical (2000mg curcumin) to be taken once daily
over 3 months, Group 3 (CSBN): Cold stimulation using cooling vest x 60 min once daily
and Browning nutraceutical (2000mg curcumin) to be taken once daily over 3 months. The
participants will then be expected to come to the centre for a total of six separate test
sessions, over a span of 6 months (2 test sessions each at week 0, 12 and 24
approximately +/-2 weeks). For each of the six test sessions,the participants will be
required to fast overnight and avoid caffeine and alcohol for 8-10 hours, only plain
water can be consumed during the fast before reporting at the CNRC in the morning between
8 to 9 am. The participants are to avoid any physical activity/exercise and alcohol on
the day prior to the visit. The test sessions will be as follows: On the 2nd visit (first
test session) at week 0, the participants will need come to CNRC in the morning and a
fasting blood sample (40 mL or approximately 8 teaspoons) and urine sample will be
collected before they undergo metabolic rate measurement with IRT focusing on their neck
and area above the collar bone in a whole body room calorimeter for the next 45 minutes.
The participants will then undergo a mild cold stimulation of about 14 degree Celsius by
wearing a cooling vest for the next 45 minutes, in which metabolic rate measurement and
IRT in the whole body calorimeter will be performed during this period. Please note that
wearing the cooling vest may lead to some shivering, but it is generally considered safe.
Upon exiting the whole body calorimeter, the participants will remove the cooling vest
and then proceed to Clinical Imaging Research Centre (CIRC) located at the basement level
of the same building, where an intravenous indwelling cannula will be inserted into an
arm vein and 20 mL (approximately 4 teaspoons) of blood and another urine sample will be
collected again. The participants will then wear the cooling vest again for approximately
another 60 min and in between they will receive an intravenous injection of a radioactive
labeled glucose called 18-FDG through the intravenous cannula. The cooling vest will be
removed just prior to the start of the PET (Positron Emission Tomography) and MRI/MRS
(Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy) that will take place over
the next 1 hour to quantify BAT (Brown Adipose Tissue) and abdominal white fat including
liver and muscle fat. The participants will also need to undergo a body composition
evaluation using dual energy X-ray absorptiometry (DXA) (approximately 20 mins duration)
which allows quantification of fat, lean and bone mass. However, the participants will be
given the option to do the DXA scan on their next/3rd visit according to their
preference. After which, the participants will be free to leave. On the 3rd visit (second
test session) at week 0, the participants will need come to CNRC in the morning for an
Oral Glucose Tolerance Test (OGTT). Anthropometric measurements taken will be height,
weight, waist circumference and hip circumference. Body composition will be measured
using an electrical impedance analyser (BIA). Blood pressure will be measured using an
automatic blood pressure monitor. A fasting blood sample (4 mL or less than 1 teaspoon)
will be collected and participants will then be required to consume a glucose drink (75g
of glucose) within 5 minutes. Subsequently after 120 min, another blood sample (4 mL or
less than 1 teaspoon) will be collected. During the entire test session, the participants
will have to stay rested and in the laboratory. Television and a workspace will be
provided for the participants use if required. At the end of 2 hours of testing, for
participants who have not undergone for the DXA scan on the 2nd visit, they will then
proceed to complete the DXA scan (approximately 20 mins duration). After which,
participants will be free to leave.The above 2 test sessions may be scheduled in any
order,but to be completed no more than 2 weeks apart. The participants will now start the
study intervention procedures as per the intervention group randomly assigned to them for
the next 12 weeks or 3 months. Participants who are assigned to group 1 / cold
stimulation (CS), will be expected to undergo a mild cold stimulation of about 14 degree
Celsius by wearing a cooling vest for approximately an hour daily for the next 12 weeks
or 3 months. Participants who are assigned to group 2 / browning nutraceutical (BN), will
be expected to consume 2000mg of curcumin (in forms of capsules) daily for the next 12
weeks or 3 months. Curcumin is a naturally-occurring polyphenol antioxidant that is found
in turmeric ginger rhizome root and has been widely known in Asia to have health
benefits. Since both substances are commonly consumed among Asians, it is relevant to
study their combined chronic clinical effects on BAT. Use of curcumin to stimulate BAT is
essentially safe as both are naturally occurring plant derived substances from Curcuma
longa rhizome. It is generally recognised as safe for human consumption. The US FDA has
approved curcumin as 'Generally Recognised as Safe' (GRAS) status and allows these to be
taken as foods ingredients. Participants who are assigned to group 3 / cold stimulation
and browning nutraceutical (CSBN), will be expected to undergo a mild cold stimulation of
about 14 degree Celsius by wearing a cooling vest for approximately an hour and, consume
2000mg of curcumin (in forms of capsules) daily for the next 12 weeks or 3 months. The
participants will then be required to come for the 4th visit (third test session) and 5th
visit (fourth test session) at week 12 (after completing the 3 months of intervention),
as per follows:
On the 4th visit (third test session) at week 12, participants will repeat the same
procedures as per that of the 2nd visit (first test session). For the 5th visit (fourth
test session) at week 12, participants will need to come to CNRC in the morning in a
fasted state and proceed first to CIRC for a 30 min MRI/ MRS only scan of BAT/WAT to
study the fat composition. Subsequent procedures will be same as that of the 3rd visit
(second test session). After which, there will be no more intervention and participants
will continue with their usual lifestyle and diet for the next 3 months (week 12 to
24).The participants will lastly be required to come for the 6th visit (fifth test
session) and 7th visit (sixth test session) at week 24 (6 months from start of study),
and repeat the same procedures as per that of the 2nd visit (first test session) and the
3rd visit (second test session) respectively. Notes: *The 2 test sessions each at week 0,
12 and 24 may be scheduled within 4 weeks from each time point. *The following test
sessions will be scheduled no more than 4 weeks apart: o First and second test sessions
for Week 0 (in any order) o Third and fourth test sessions for Week 12 (in any order) o
Fifth and sixth test sessions for Week 24 (in any order)