Raspberry Ketones

Summary (The Good, The Bad, and all other Essential Benefits/Effects/Facts Information)

Raspberry ketones are the compound responsible for many flavoring and aromatic qualities of cosmetics and processed foods.

In the body and in high doses, it can exert fat burning effects on various areas of the fat cell. These effects on the cell may be similar to Ephedrine and Synephrine.

They have been used as a supplement for a while, although all evidence on their effects on fat cells is in vitro (in a test tube) at this moment in time.

Also Known As

4-(4-hydroxyphenyl) butan-2-one, p-hydroxybenzyl acetone

Is a Form of

• Fat-Burner
• Health Support

How to Take (recommended dosage, active amounts, other details)

A typical dose of raspberry ketones is around 100mg, although the most effective or cost-effective dose is not really known.

Things to Note

• Raspberry Ketones are non-stimulatory

• Raspberry Ketones have a slight raspberry aroma and taste, although a slight aroma/taste of 'plastic' tends to also be present

Caution Notice (just some FYI - if needed)

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Detailed Summary

1. Structure and Sources
   1. Sources
   2. Structure
2. Pharmacology
   1. Metabolism
3. Effects on lipolysis and fat cells
4. Interactions with Hormones
5. Cosmetic usage
6. As Raspberry leaf tea
   1. Interactions with pregnancy
7. Safety and Toxicity

Edit1. Structure and Sources

1.1. Sources

Raspberry Ketones (also known as 4-(4-hydroxyphenyl) butan-2-one) are an extract from Red raspberries usually used as a scenting and flavoring agent in foods and cosmetics.^[1] It has a structure similar to Capsaicin and Synephrine, sharing a 1,3,7-cyclohexene group with a carbon tail.^[2]

It can naturally be found in many foods, most notably raspberries (in which case it is synthesized from coumaroyl-CoA), however most raspberry ketone is synthesized^[3] or produced via bacteria^[4][5] due to its high demand in cosmetics and as a flavoring agent.

Estimated intake of raspberrry ketone without supplementation is 0.42mg/kg bodyweight,^[6] consumed through foods or products using Raspberry ketones as coloring or flavoring agent.

1.2. Structure

Raspberry ketones have a similar structure to Synephrine and Ephedrine. The only changes are in the tail attached to the benzene ring, in which the 2 carbon is double bonded to oxygen (which is the ketone group from which its name is derived from) rather than being an amine group.

Edit2. Pharmacology

2.1. Metabolism

After oral ingestion, Raspberry ketones are targeted by sulfation and glucuronidation enzymes of the hepatic P450 enzyme system.^[7]

It (Raspberry ketones, aka 4-(4-hydroxylphenyl)butan-2-one) can be metabolized via ring conjugation (resulting in 4-(4-hydroxylphenyl)butan-1,2-diol) or via side-chain oxidation (resulting in 4-(4-hydroxylphenyl)butan-2,3-diol).^[7] The main metabolite of raspberry ketones is urinary in nature, either the sulphate or glucuronide conjugate of said derivations.^[7]

Edit3. Effects on lipolysis and fat cells

10uM of Raspberry ketones in vitro have been shown to increase the amount of glycerol in adipose (from fatty acid separation from TGs) threefold and increased fatty acid oxidation while suppressing triglyceride accumulation (indicative of ingested fatty acids).^[2]

After four days of 10uM administration, cellular and secreted levels of adiponectin were highly increased in the same fat cells.^[2]

In rats fed raspberry ketone and overfed in general, it has been shown to suppress fat accumulation while increasing markers associated with fat burning (such as lipoprotein lipase translocation and norepinephdrine induced lipolysis).^[8] Past toxicological studies note a 'slight but significant decrease in weight' at 1% of the diet as raspberry ketones, but the amount was not specified.^[6]

The exact mechanisms of these actions are not yet known, and no human interventions have been conducted.

Edit4. Interactions with Hormones

In vitro studies with breast cancer cell lines suggest that Raspberry Ketones can inhibit the androgen receptor, with an IC₅₀ value of 252uM.^[9]

Edit5. Cosmetic usage

Raspberry ketones, used topically, have been found to increase IGF-1 production in the dermis (skin) and may lead to increased hair growth at an 0.01% solution (applied once daily for 5 months).^[10] These effects seem to be mediated through vanilloid-receptor 1 (VR1) activation, similar to Capsaicin (another compound with a similar structure, but a longer tail).

Raspberry ketones have also been linked to increasing skin elasticity at a solution of 0.01% in human females.^[10]

Edit6. As Raspberry leaf tea

Raspberry leaf tea is a herbal medicine traditionally recommended to pregnant women, and contains various compounds such as 'gallo- and ellagitannins, flavonoids, vitamin C, various alcohols, aldehydes, ketones, organic acids, terpenoids, carbohydrates and glycosides'.^[11] The ketones this list refers to are the raspberry ketones, most notably 4-(4-hydroxyphenyl)butan-2-one.

6.1. Interactions with pregnancy

Raspberry leaf tea is typically recommended to pregnant women to shorten labor^[12][13] The mechanism of which is not yet elucidated, but does not appear to be mediated by uterine contractility.^[14]

Adverse effects are not usually seen at dosages of 1.2-2.4g raspberry leaf daily, but neither are statistically significant benefits to labour length.^[15][11][13]

In regards to safety, a recent review suggested that not enough information exists to draw a conclusion due to small sample sizes.^[11]

Edit7. Safety and Toxicity

There is not much evidence on the safety threshold on Raspberry ketone in humans due to its relatively new introduction into supplementation.

Fat cells show no cytotoxicity, however, at doses up to five times (100um) the effective dose noted above.^[2] In rats, intake of up to 100mg/kg bodyweight does not cause any short-term alterations in markers of blood health^[6], and the LD⁵⁰ is established at around 1.3-1.4g/kg bodyweight.^[6]

Human Clinical Trial Results

Confidence	Attribute	Result in Studies	References
C	Skin Elasticity		Show Study
C	Hair Regrowth		Show Study

Scientific Support & Reference Citations

References

1. The application of raspberry ketone to successful body care
2. Park KS. Raspberry ketone increases both lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. Planta Med. (2010)
3. Cation-Exchanged Montmorillonite-Catalyzed Facile Friedel-Crafts Alkylation of Hydroxy and Methoxy Aromatics with 4-Hydroxybutan-2-one To Produce Raspberry Ketone and Some Pharmaceutically Active Compounds
4. Beekwilder J, et al. Microbial production of natural raspberry ketone. Biotechnol J. (2007)
5. Feron G, et al. Microbial production of 4-hydroxybenzylidene acetone, the direct precursor of raspberry ketone. Lett Appl Microbiol. (2007)
6. Gaunt IF, et al. Acute and short-term toxicity of p-hydroxybenzyl acetone in rats. Food Cosmet Toxicol. (1970)
7. Sporstøl S, Scheline RR. The metabolism of 4-(4-hydroxyphenyl)butan-2-one (raspberry ketone) in rats, guinea-pigs and rabbits. Xenobiotica. (1982)
8. Morimoto C, et al. Anti-obese action of raspberry ketone. Life Sci. (2005)
9. Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay
10. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans
11. Holst L, Haavik S, Nordeng H. Raspberry leaf--should it be recommended to pregnant women. Complement Ther Clin Pract. (2009)
12. Parsons M, Simpson M, Ponton T. Raspberry leaf and its effect on labour: safety and efficacy. Aust Coll Midwives Inc J. (1999)
13. Parsons M, Simpson M, Wade K. Labour and the raspberry leaf herb. Pract Midwife. (2000)
14. Jing Zheng, et al. The effects of commercial preparations of red raspberry leaf on the contractility of the rat's uterus in vitro. Reprod Sci. (2010)
15. Simpson M, et al. Raspberry leaf in pregnancy: its safety and efficacy in labor. J Midwifery Womens Health. (2001)
16. Harada N, et al. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans. Growth Horm IGF Res. (2008)

Last Updated: Apr 16, 2012 10:48:13