Author: Gianpiero Pescarmona Date: 02/10/2007
Ministero Della Salute: Alimenti Particolari e Integratori Luglio 2009
List of food additives
These compounds are ......
Introduction
There has been a lot of buzz in the media about raspberry ketones lately, especially ever since Dr. Oz mentioned these substances on his TV show and touted them as a wonderful fat burning aid recently. So what are they, what do they do and can they really help you burn more fat and achieve the lean body you want? We will explain what these substances are and what kind of action they have in our bodies in just a moment. But the exciting news is that they do seem to be able to help us burn fat and stay leaner. Let’s explore these wonderfully aromatic compounds closely so you can understand their actions and what impact they can have on your body goals. They can be ingested orally and metabolized when they are in the blood stream they have effects on lipolysis on our fat cells.
Raspberry ketone is a natural phenolic compoundred raspberries. p-Hydroxyphenylbutan-2-one, the characteristic aroma compound of raspberries (Rubus idaeus L.), is synthesized from p-coumaryl-coenzyme A and malonyl-coenzyme A in a two-step reaction sequence that is catalyzed by benzalacetone synthase and benzalacetone reductase (W. Borejsza-Wysocki and G. Hrazdina [1994] Phytochemistry 35: 623-628). Benzalacetone synthase condenses one malonate with p-coumarate to form the pathway intermediate p-hydroxyphenylbut-3-ene-2-one (p-hydroxybenzalacetone) in a reaction that is similar to those catalyzed by chalcone and stilbene synthases. We have obtained an enzyme preparation from ripe raspberries that was preferentially enriched in benzalacetone synthase (approximately 170-fold) over chalcone synthase (approximately 14-fold) activity. This preparation was used to characterize benzalacetone synthase and to develop polyclonal antibodies in rabbits. Benzalacetone synthase showed similarity in its molecular properties to chalcone synthase but differed distinctly in its substrate specificity, response to 2-mercaptoethanol and ethylene glycol, and induction in cell-suspension cultures. The product of the enzyme, p-hydroxybenzalacetone, inhibited mycelial growth of the raspberry pathogen Phytophthora fragariae var rubi at 250 [mu]M. We do not know whether the dual activity in the benzalacetone synthase preparation is the result of a bifunctional enzyme or is caused by contamination with chalcone synthase that was also present. The rapid induction of the enzyme in cell-suspension cultures upon addition of yeast extract and the toxicity of its product, p-hydroxybenzalacetone, to phytopathogenic fungi also suggest that the pathway may be part of a plant defense response.)
Preparation
Since the natural abundance of raspberry ketone is very low, it is prepared industrially by a variety of methods from chemical intermediates. One of the ways this can be done is through a crossed aldol-catalytic hydrogenation. In acetone and sodium hydroxide, 4-hydroxybenzaldehyde can form the α,β-unsaturated ketone. This then goes through catalytic hydrogenation to produce raspberry ketone. This method produces a 99% yield. It's a multi-stage reaction that starts with a condensation of p-Coumaroyl-CoA with Malonyl-CoA.
other ways of making it?
It can be made in the laboratory by more than one route. One convenient two-step synthesis involves, first, the crossed-aldol condensation of 4-hydroxybenzaldehyde with propanone, forming (4-(4'-hydroxyphenyl)-3-buten-2-one). This double-bond in the side-chain can then be catalytically hydrogenated forming rheosmin. Another method that has been described involves a Friedel-Crafts alkylation of phenol by 4-hydroxybutan-2-one, using a cation-exchanged montmorillonite catalyst
Effects
Does it have any other uses, apart from flavourings?
Tests on mice indicate that it has an antiobese effect, believed to be due to its increasing lipolysis and fatty acid oxidation. As far as is known, no tests on humans have been reported. Just like other ketone bodies, raspberry ketones encourage our bodies to free up lipids or fats for fuel. Raspberry ketones seem to do this by increasing the amount of glycerol in our adipose tissue (from fatty acid separation) as much as threefold. Additionally, they increase fatty acid oxidation while suppressing triglyceride accumulation. Simply put, they give our fat cells the signals to more freely release fat as fuel, and help our bodies resist fat accumulation. More precisely, red raspberry ketones do all this action by increasing the levels of a protein hormone called adiponectin. Adiponectin is a hormone produced by our fat cells that regulates the metabolism of lipids and glucose in the fat cell, and also influences our own body’s response to insulin. This hormone decreases triglyceride production, has an anti-inflammatory effect in arterial walls, decreases glucose production in the liver, and increases insulin sensitivity. Adiponectin is the protein product of an adipose tissue-specific factor, isolated and termed APM1. Low levels of adiponectin are found in people who are obese, and high levels are seen in people who have a tough time storing fat. The net of this is that if your adiponectin levels are higher then you will more than likely have an easier time getting lean and staying lean. The higher amounts of raspberry ketones in your body means higher amounts of adiponectin, which means more fat released as fuel. Now you should know that these things don’t work in a vacuum and if your diet isn’t complimentary to fat burning then your results will be poor. After all, you can’t eat ten pizzas, take some rasberry ketones and think that your body won’t want to store extra calories as fat. But if your diet is right, and you are exerting more energy than you are taking in, then adding raspberry ketones can help you effectively raise adiponectin levels and in turn help you lose a much higher amount of body fat. Can taking more red raspberry ketones help us stay lean, burn fat and achieve some to the body goals that we want? As you have probably already guessed from our earlier discussion the answer is yes. The evidence seems to suggest that raspberry ketones can help us lose fat and keep it off. I do believe that adding red raspberry ketones to your good daily diet in the form of a fat burner like Scorch or similar product can have a positive impact on your body’s ability to burn fat faster and help you keep it off. The dietary administration of RK to male mice has been reported to prevent high-fat diet-induced elevation in body weight and to increase lipolysis in white adipocytes. To elucidate a possible mechanism for the antiobesity action of RK, its effects on the expression and the secretion of adiponectin, lipolysis, and fatty acid oxidation in 3T3-L1 were investigated. Treatment with 10 µM of RK increased lipolysis significantly in differentiated 3T3-L1 cells. An immunoassay showed that RK increased both the expression and the secretion of adiponectin, an adipocytokine mainly expressed and secreted by adipose tissue. In addition, treatment with 10 µM of RK increased the fatty acid oxidation and suppressed lipid accumulation in 3T3-L1 adipocytes. These findings suggest that RK holds great promise as an herbal medicine since its biological activities alter the lipid metabolism in 3T3-L1 adipocytes.
Safety
Little is known about the long term safety of raspberry ketone supplements. In 1965, the Food and Drug Administration placed raspberry ketone ongenerally recognized as safe (GRAS) status for the small quantities used as a food additive. The first study was not blinded (not controlled for bias) and it examined weight-gain in a few male mice fed a high fat diet plus high dose raspberry ketone. It also analyzed some rat liver cells exposed to raspberry ketone. The second study was also not blinded (not controlled for bias) and did not involve humans or any other animal, but instead, just looked at fat cells exposed to raspberry ketone in a petri dish. Limited to one or two small studies done on rats we don’t know very much about the short or long-term effects of using raspberry ketones as a dietary supplement, which involves much higher dosages than are used in food manufacturing. For people with high blood pressure, diabetes, kidney disease, anxiety disorders, or for who are pregnant or on asthma medicine, raspberry ketones are not advisable
