10:46 PM Ian
Surprisingly, the research in question only looked at the effects of naringenin on human and rat liver cells in the laboratory. This very preliminary research has certainly not identified a “cure” for diabetes. It only concentrated on how the chemical affected the fat metabolism of cells rather than processes directly related to diabetes. Until clinical trials are carried out in humans, it is not possible to say whether naringenin might be an effective medical treatment or whether it carries side effects.
Grapefruit is known to interact with enzymes in the body that break down many drugs. This can mean that consuming too much grapefruit can interfere with people’s drug treatment and cause harmful effects. Diabetics or other individuals taking medications should not attempt to replace or supplement their prescribed medication with grapefruit, as some news reports might suggest.
Where did the story come from?
The study was carried out by researchers from Shriners Hospitals in Boston and other research centres in the US, Israel and France. The study was funded by the US National Institute of Diabetes and Digestive and Kidney Diseases, the European Research Council and the Harvard Clinical Nutrition Research Centre. It was published in PLoS One, the peer-reviewed open-access journal of the Public Library of Science.
This study was covered by the Daily Mirror, Daily Mail and Daily Express. All of these newspapers claim that grapefruit can “fight” or “cure” diabetes, and that it has the same benefits as two diabetes drugs. These claims wildly over-extrapolate the findings of this preliminary laboratory research. None of the newspaper reports clarify that this was only laboratory research on isolated cells or that any potential benefits or side effects of naringenin will remain unclear until there are human studies.
What kind of research was this?
This was laboratory research looking at how a chemical called naringenin, found in grapefruit, affects liver cells under laboratory conditions.
The researchers were interested in doing this as studies have suggested that naringenin can reduce the level of one type of cholesterol (LDL) in humans and other animals. This study aimed to work out the chemical mechanism by which naringenin might have this effect. This type of study is appropriate for answering this type of question. However, it would not be appropriate to tell us what the effects of naringenin on the body as a whole would be.
What did the research involve?
Naringenin has anti-inflammatory properties and induces a chemical reaction called beta oxidation. The researchers say that these properties suggest it could be acting in a similar way to drugs such as fibrates and glitazones, which are used to treat people with high levels of fats in the blood and to treat type 2 diabetes respectively. Both increase the activity of proteins called PPAR alpha and PPAR gamma in cells.
Previous studies suggested that naringenin reduces the activity of an enzyme called HMGR, which is involved in cholesterol metabolism. HMGR is in turn controlled by a protein called LXR alpha, and the researchers thought that naringenin could be having its effect on HMGR by interacting with LXR alpha. Cholesterol-lowering statin drugs work by targeting HMGR.
To investigate the interactions reported in previous studies, the researchers took took samples of human cells (including liver cells) grown in the laboratory and treated them with naringenin. They looked at the effects on LXR alpha and the PPAR alpha and gamma proteins targeted by fibrate and glitazone drugs.
LXR alpha and both PPAR proteins are involved in controlling the activity of certain genes in the cell, so the researchers then looked at whether naringenin affected the activity of genes controlled by PPAR alpha and LXR alpha.
Finally, the researchers tested the effect of naringenin on freshly extracted rat liver cells.
What were the basic results?
The researchers found that naringenin did make PPAR alpha and PPAR gamma more active in human cells grown in the laboratory. They found that naringenin affected PPAR activity in liver cells in a similar manner to the drug ciglitazone. Naringenin inhibited the activity of the LXR alpha protein in human cells grown in the laboratory.
Treating liver cells with naringenin increased the activity of those genes involved with fatty acid oxidation that are controlled by PPAR alpha. Treatment also reduced the activity of genes controlled by LXR alpha. These changes in gene expression suggested that the cells were shifting from making fats and cholesterol to breaking down fats.
Finally, the researchers found that treating freshly extracted rat liver cells with naringenin for 24 hours reduced their production of a type of fat called triglycerides, and also reduced their production of bile salts.
How did the researchers interpret the results?
The researchers concluded that: “Our findings explain the myriad effects of naringenin and support its continued clinical development. Of note, this is the first description of a non-toxic, naturally occurring [LXR alpha] inhibitor.”
This complex laboratory research suggests that naringenin can affect proteins and genes involved in fat metabolism in liver cells. Although the effect that it has on the cells is similar to the effects of drugs such as the fibrates and glitazones, this does not necessarily mean that naringenin could be used to treat the same conditions as the fibrates and glitazones. In the body different drugs interact with different subsets of the numerous proteins and molecules in the body in different ways. It is these complex interactions which will determine their overall effects. This study has only assessed interactions of naringenin with a small number of proteins in cells in the laboratory, and cannot tell us what the overall balance of positive and negative effects will be on the whole body.
Further points to consider:
* This study focused on the fat-metabolising effects of narangenin, suggesting a potential for treating people with high cholesterol rather than diabetes, as was reported in newspapers.
* The reported link to diabetes is more tenuous considering that the only association that has been made in this study is likening the action of naringenin to the effect of glitazone drugs. These are not the drugs of choice in diabetes; they are only used in certain circumstances. Importantly, they have been identified to carry cardiovascular risk and are used under close supervision.
* This study cannot tell us whether eating grapefruit or drinking grapefruit juice would provide sufficient naringenin to act upon cells in the same way as observed in this lab experiment.
* Although the authors of the current research describe an uncontrolled study of naringenin in people with high cholesterol, further randomised controlled studies in people with this or other conditions would be required to determine what its beneficial and adverse effects might be.
Grapefruit is also known to interact with enzymes in the body that break down many drugs. This can mean that consuming too much grapefruit (e.g. by drinking grapefruit juice) can interfere with people’s drug treatment and cause harmful effects. For example, people taking the statin simvastatin to control their cholesterol levels are advised to avoid drinking grapefruit juice as it can increase the chance of side effects from the drug. Grapefruit also is known to interact with a range of cardiovascular drugs and other medicines.
Diabetics or other individuals taking medications should not increase their consumption of grapefruit or grapefruit juice based on this study’s findings.