Raspberry Ketone Fundamentals

Authored by Dr. Brianna Stubbs • 
November 27, 2017
ketosis

Raspberry ketone is the compound responsible for many flavoring and aromatic qualities of cosmetics and processed foods. Structurally, raspberry ketones are completely different to physiological ketones that are made by the body or consumed in exogenous ketone supplements. These natural ketones are beta-hydroxybutyrate, acetoacetate and acetone. Raspberry ketone does not get used as energy in the body and does not act as a signal in the same way as physiological ketones. Supplements containing raspberry ketone are marketed for use as a fat burning tool. However, the scientific raspberry ketone results in humans are limited. What’s more, the raspberry ketone dosage used in the existing animal studies is far higher than it would be possible or safe for humans to consume.  

Raspberry Ketone Structure and Natural Occurrence

Raspberry ketone has a similar structure to Synephrine and Ephedrine.

It is found naturally in many food stuffs, most notably raspberries. Most raspberry ketone used commercially is synthesized or produced via bacteria. Normally, humans consume small amounts of raspberry ketones through processed foods which have raspberry ketone added as a flavoring agent.

The human body does not produce raspberry ketones naturally. 

Uses and Evidence

Raspberry ketones are marketed for use as as a fat burning compound. 

In vitro evidence

There is mixed evidence as to whether raspberry ketone can stimulate fat release (lipolysis). Experiments using ‘adipose cell lines’ have shown there may be a positive effect of raspberry ketone. One study in an adipocyte cell line model noted that 10µM of the compound tripled glycerol release, an indicator of lipolysis 1 . A later, more comprehensive study in the same 3T3-L1 adipocyte cell line found that 10µM raspberry ketone increased the activation of several genes involved in lipolysis, including adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL)2  .

In contrast, studies on the effects of raspberry ketone on lipolysis in ‘primary adipose cells’ are not consistent with those in ‘adipose cell lines’. ‘Primary cells’ directly taken from animal adipose tissue are often better suited to model in vivo processes than ‘adipose cell lines’, which can have substantial genetic drift from being kept in continuous culture. A study using primary adipose cells from a rodent model failed to show any lipolysis-stimulating effects with raspberry ketone alone 3 . This study did note that concentrations in the range of 1-10mM stimulated lipolysis in the presence of norepinephrine. Therefore, raspberry ketone may increase norepinephrine- mediated lipolysis in primary adipocytes. There was no detectable binding of raspberry ketone to β-adrenergic receptors, and more research is needed to examine whether raspberry ketone augments norepinephrine- mediated lipolysis in vivo.

In vivo and human evidence

There is very limited evidence that raspberry ketone alters fat metabolism in animals or humans.  Rats fed 0.5-2% raspberry ketone (daily total intake = 0.5 - 2.2 g/kg) during periods of high fat overfeeding noted dose-dependent anti-obesity actions in preventing body weight gain.  However, the group fed 2% raspberry ketones still gained more weight than the control group fed a normal diet 3 . Other toxicological studies in animals also noted decreases in body weight associated with raspberry ketones at 1% of the diet 4 . The doses of raspberry ketone used in this study are not practical for human consumption. 

Raspberry ketone may have some beneficial influences on liver fat buildup, although this has only been tested in rat models, and may not be true in humans. Also, high, impractical doses of raspberry ketone were used to achieve these effects.

The one human study to investigate the effects of raspberry ketone was highly confounded. Raspberry ketone was co-administered with several other supplements in a "METABO" formulation (raspberry ketone paired with caffeine, capsaicin, garlic, ginger and Citrus aurantium as a source of synephrine), so the benefits cannot be traced back to raspberry ketone per se. This study did find  a fat loss of 7.8% relative to the 2.8% in placebo, and weight loss of 2% relative to 0.5% in placebo, without detectable differences in caloric intake 5

Raspberry Ketone Safety

Little is known about the long-term safety of raspberry ketone supplement. Because it is chemically related to the stimulant synephrine, there are some concerns about its safety 4 . Toxicological models indicate a potential for cardiotoxic effects, as well as effects on reproduction and development 6

In 1965, the US Food and Drug Administration classified raspberry ketone as generally recognized as safe (GRAS) for the small quantities used to flavor foods. In the UK, raspberry ketone supplements are on the Food Standards Agency's unauthorized list.

Scientific Citations

1.Park KS. Raspberry ketone increases both lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. Planta Med. 2010;76(15):1654-8.
2.Park KS. Raspberry ketone, a naturally occurring phenolic compound, inhibits adipogenic and lipogenic gene expression in 3T3-L1 adipocytes. Pharm Biol. 2015;53(6):870-5.
3.Morimoto C, Satoh Y, Hara M, Inoue S, Tsujita T, Okuda H. Anti-obese action of raspberry ketone. Life Sci. 2005;77(2):194-204.
4.Gaunt IF, Sharratt M, Colley J, Lansdown AB, Grasso P. Acute and short-term toxicity of p-hydroxybenzyl acetone in rats. Food Cosmet Toxicol. 1970;8(4):349-58.
5.Lopez HL, Ziegenfuss TN, Hofheins JE, et al. Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women. J Int Soc Sports Nutr. 2013;10(1):22.
6.Bredsdorff L, Wedebye EB, Nikolov NG, Hallas-møller T, Pilegaard K. Raspberry ketone in food supplements--High intake, few toxicity data--A cause for safety concern?. Regul Toxicol Pharmacol. 2015;73(1):196-200.
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