Two compounds found in red grapes and oranges combined could
treat diseases
A combination of
two compounds found in red grapes
and oranges could be used to improve the health of people with diabetes, and
reduce cases of obesity and heart disease.
The
find has been made by University of Warwick researchers who now hope that their
discovery will be developed to provide a treatment for patients.
Professor
Thornalley who led research said: "This is an incredibly exciting
development and could have a massive impact on our ability to treat these
diseases. As well as helping to treat diabetes and heart disease it could
defuse the obesity time bomb."
The
research 'Improved glycemic control and vascular function in overweight and
obese subjects by glyoxalase 1 inducer formulation' has been published in the
journal Diabetes, and received funding from
the UK's innovation agency, Innovate UK. The project was a collaboration
between the University of Warwick and University Hospitals Coventry and
Warwickshire (UHCW) NHS Trust.
A
team led by Paul Thornalley, Professor in Systems Biology at Warwick Medical
School, studied two compounds found in fruits but not usually found together.
The compounds are trans-resveratrol (tRES) -- found in red grapes, and
hesperetin (HESP) -- found in oranges. When given jointly at pharmaceutical
doses the compounds acted in tandem to decrease blood glucose, improve the
action of insulin and improve the health of arteries.
The
compounds act by increasing a protein called glyoxalase 1 (Glo1) in the body
which neutralises a damaging sugar-derived compound called methylglyoxal (MG).
MG is a major contributor to the damaging effects of sugar. Increased MG
accumulation with a high energy diet intake is a driver of insulin resistance
leading to type 2 diabetes, and also damages blood vessels and impairs handling
of cholesterol associated with increased risk of cardiovascular diseases.
Blocking MG improved health in overweight and obese people and will likely help
patients with diabetes and high risk of cardiovascular disease too. It has
already been proven experimentally that blocking MG improves health impairment
in obesity and type 1 and type 2 diabetes.
Although
the same compounds are found naturally in some fruits, the amounts and type
required for health improvement cannot be obtained from increased fruit
consumption. The compounds that increase Glo1 and are called a 'Glo1 inducer'.
Pharmaceutical doses for patients with obesity, diabetes and high risk of heart
disease could be given to patients in capsule form.
Professor
Thornalley increased Glo1 expression in cell culture. He then tested the
formulation in a randomised, placebo-controlled crossover clinical trial.
Thirty-two
overweight and obese people within the 18-80 age range who had a BMI between
25-40 took part in the trial. They were given the supplement in capsule form
once a day for eight weeks. They were asked to maintain their usual diet and
their food intake was monitored via a dietary questionnaire and they were also
asked not to alter their daily physical activity. Changes to their sugar levels
were assessed by blood samples, artery health measured by artery wall
flexibility and other assessments by analysis of blood markers.
The
team found that the highly overweight subjects who had BMIs of over 27.5 with
treatment displayed increased Glo1 activity, decreased glucose levels, improved
working of insulin, improved artery function and decreased blood vessel
inflammation. There was no effect of placebo.
Professor
Thornalley said: "Obesity, type 2 diabetes and cardiovascular disease are
at epidemic levels in Westernised countries. Glo1 deficiency has been
identified as a driver of health problems in obesity, diabetes and
cardiovascular disease."
"Diabetic
kidney disease will be the initial target to prove effective treatment for
which we are currently seeking commercial investors and partners. Our new
pharmaceutical is safe and expected to be an effective add-on treatment taken
with current therapy.
"The
key steps to discovery were to focus on increasing Glo1 and then to combine
tRES and HESP together in the formulation for effective treatment.
"As
exciting as our breakthrough is it is important to stress that physical
activity, diet, other lifestyle factors and current treatments should be
adhered to."
Professor
Martin O Weickert, Consultant in Diabetes and Endocrinology at UHCW NHS Trust,
and co-applicant for the grant, said: "We were really excited to
participate in this study with Warwick Medical School, as taking part in
world-leading research makes a real difference to our patients both now and in
the future.
"As
well as the positive effects for the UHCW patients who took part in the trial,
we hope this study will lead to new treatments to help patients with diabetes
and cardiovascular diseases all over the world."
Prof.
Thornalley and his team are now hoping manufacturers will want to explore the
use of the compound as pharmaceutical products.
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