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‘Statin-like’ bergamot extract offers novel approach in fight against ‘diabesity’

By Elaine WATSON , 23-Oct-2012

A new product containing a patented extract of the citrus fruit bergamot boasting ‘statin-like’ qualities - without the side effects - has been launched in the US claiming to tackle the key components of metabolic syndrome.

BergaMet MEGA, which has just launched in Europe and has been successful in Australia, is now available to US consumers online and is distributed directly to health care practitioners, its US distributor Nathealth Solutions told NutraIngredients-USA.

The multiple properties of the bergamot fruit allow it to work at many levels in cardiovascular prevention  

‘Diabesity’ or metabolic syndrome, is characterized by a group of metabolic risk factors including central obesity, high triglycerides and LDL cholesterol, elevated blood pressure, insulin resistance or glucose intolerance, and being in a pro-inflammatory state (eg. high C-reactive protein levels in the blood).

Those with some or all of the above factors are at higher risk of developing type 2 diabetes or heart conditions.

While many plant-based ingredients are proven to have beneficial effects on one of these risk factors, a growing body of clinical evidence suggests that bergamot fruit - which is grown in the Calabria region of Southern Italy - has a positive impact on several of them, claimed cardiologist Ross Walker, MD, chief international medical advisor for Nathealth Solutions.

“The multiple properties of the bergamot fruit allow it to work at many levels in cardiovascular prevention. A recent study from Italy has also demonstrated a synergistic action with statins.”

Statin-like properties

A 30-day randomized controlled study * published last April in the journal Fitoterapia led by researchers at the Department of Cardiology at the University in Rome on the effect of bergamot extract in diet-induced hyperlipemia in Wistar rats and in 237 patients suffering from hyperlipemia, showed that it reduced total and LDL cholesterol, triglycerides and blood glucose, while raising HDL.

The authors added: “On the basis of our data, bergamot extract oral supplements contribute to lowering plasma cholesterol and lipids in a rat model of diet-induced hyperlipemia and in patients, in a range of potency comparable with low dose statins.

“Thus they offer a safe alternative for patients suffering from statins toxicity. In addition, the possibility to reduce blood glucose by 15–25% suggests a phytotherapeutic approach to control the prediabetic states in patients with metabolic syndrome.”

Mechanism of action

But what is the mechanism of action?

Bergamot has a unique profile of flavonoid and flavonoid glycosides in its juice and albedo (the white coating under the rind) such as neoeriocitrin, neohesperidin, naringin, rutin, neodesmin, rhoifolin and poncirin, which have been shown to have positive cardiovascular effects in multiple animal studies, added the authors.

“Previous data showed that citrus peel extracts, rich in pectins and flavonoids, cause lowering of cholesterol levels by modulating hepatic HMG-CoA levels, possibly by binding bile acids and increasing the turnover rate of blood and liver cholesterol.

“Since bergamot juice was shown to enhance the excretion of fecal sterols in rats, such a mechanism may contribute to its hypolipemic and hypoglycemic effect found in patients under bergamot extract treatment.

“Evidence also exists that dietary hesperetin reduces hepatic TG accumulation and this is associated with the reduced activity of TG synthetic enzymes, such as phosphatidate phosphohydrolase.

 “In addition, the classical glycoside derivative of naringenin, which is naringin, has been shown to inhibit hepatic HMG-CoA reductase. Therefore it is likely that melitidine and brutieridine [derivatives of hesperetin and naringenin] in concert with naringin and other flavonone glycosides, might be responsible for the striking potency of bergamot extract in reducing cholesterol levels.”

Meanwhile, the antioxidant and anti-inflammatory effects of bergamot extracts also had beneficial effects on measures of endothelial function, they said.

BergaMet activates AMPK, the master regulator in metabolic pathways involved in glucose and fatty acid metabolism

Asked how BergaMet might affect abdominal obesity, a spokesperson for Nathealth Solutions said: “BergaMet activates AMPK, which is the master regulator involved in metabolic pathways involved in glucose and fatty acid metabolism.

“AMPK is also an important target of [diabetes drug] metformin. To ensure the energy production, AMPK not only facilitates glucose uptake, but triggers several catabolic and blocks anabolic pathways. First of all, AMPK prevents the accumulation of fat by modulating downstream-signalling components like acetyl-CoA carboxylase (ACC) and HMG-CoA reductase. AMPK phosphorylates and inhibits ACC1 activity, which blocks the rate-limiting step in fatty acid synthesis.

“On the other hand phosphorylation of ACC2 by AMPK augments fatty acid oxidation, which is a catabolic pathway for fat deposits. According to the studies of the ‘fatty mice model’, a high-fat diet reduces the basal activity levels of AMPK, suggesting that a certain level of AMPK basal activity may be necessary to prevent fat accumulation.”

One BergaMet tablet contains 650 mg of bergamot dehydrated juice. Recommended dosage is one tablet twice daily, 20-30 minutes before the two largest meals of the day.  

* Hypolipemic and hypoglycaemic activity of bergamot polyphenols: From animal models to human studies (Mollace et al)

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