Warwick University. UK: Scientists at the University of Warwick have discovered that ‘good’ cholesterol is turned ‘bad’ by a sugar-derived substance. The substance, methylglyoxal - MG, was found to damage ‘good’ HDL
cholesterol, which removes excess levels of bad cholesterol from the
body.
Low levels of HDL, High Density Lipoprotein, are closely linked to
heart disease, with increased levels of MG being common in the elderly
and those with diabetes or kidney problems.
Supported by funding from the British Heart Foundation (BHF) and published in Nutrition and Diabetes, the researchers discovered that MG destabilises HDL and causes it to lose the properties which protect against heart disease.
HDL damaged by MG is rapidly cleared from the blood, reducing its HDL
content, or remains in plasma having lost its beneficial function.
Lead researcher Dr Naila Rabbani, of the Warwick Medical School, says
that: “MG damage to HDL is a new and likely important cause of low and
dysfunctional HDL, and could count for up to a 9% risk of heart
disease”.
There are currently no drugs that can reverse low levels of HDL, but
the Warwick researchers argue that by discovering how MG damages HDL has
provided new potential strategies for reducing MG levels.
Commenting on the research’s implications Dr Rabbani said:
“By understanding how MG damages HDL we can now focus on developing
drugs that reduce the concentration of MG in the blood, but it not only
be drugs that can help.
“We could now develop new food supplements that decrease MG by
increasing the amount of a protein called glyoxalase 1, or Glo 1, which
converts MG to harmless substances.
“This means that in future we have both new drugs and new foods that
can help prevent and correct low HDL, all through the control of MG.”
A potentially damaging substance, MG is formed from glucose in the
body. It is 20,000 times more reactive than glucose it damages arginine
residue (amino acid) in HDL at functionally important site causing the
particle to become unstable.
Glo1 converts MG to harmless substances and protects us. MG levels
are normally kept low in the body to maintain good health but they
slowly increase with ageing as Glo1 slowly becomes worn out and is only
slowly replaced.
Dr Rabbani says: “We call abnormally high levels of MG ‘dicarbonyl
stress’. This occurs in some diseases – particularly diabetes, kidney
dialysis, heart disease and obesity. We need sufficient Glo1 to keep MG
low and keep us in good health.”
Dr Shannon Amoils, Senior Research Advisor at the BHF, which funded the study, said:
“Dr Rabbani’s study shows us how the ‘good cholesterol’, HDL, can be
damaged by a compound produced by the breakdown of sugar. This compound
is increased in the circulation in people with diabetes.
“This interesting finding adds to evidence that under certain
conditions, HDL can be modified so that it loses its heart protective
effects, and that regarding HDL as ‘good cholesterol’ in all
circumstances may be too simplistic.
“If the modified HDL cholesterol that Dr Rabbani is studying is found
in large numbers of people with diabetes, the culprit compound that
damages it could potentially be targeted with a drug to block its
harmful action or to remove it from the circulation.”