Raspberry ketones are the compound responsible for many flavoring and aromatic qualities of cosmetics and processed foods.
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.
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4-(4-hydroxyphenyl) butan-2-one, p-hydroxybenzyl acetone
The current rat evidence uses a dosage range of 0.545-2.18g/kg, which correlates to a human estimated dose of 80-340mg/kg or, for humans:
Due to these doses being comparatively high relative to other fat burning compounds, the standard supplemental dosage of raspberry ketones is in the 100-200mg range. It is unsure if any of the above doses are optimal or even effective.
The concentration which is required to have fat burning effects is astronomically high, and the oral doses used in the rat studies similarly high. Low oral doses of raspberry ketones really need to be tested, but I honestly don't expect much from them.
They make your burps taste nice-ish though
The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Raspberry Ketones has in your body, and how strong these effects are.
|Grade||Level of Evidence|
|A||Robust research conducted with repeated double blind clinical trials|
|B||Multiple studies where at least two are double-blind and placebo controlled|
|C||Single double blind study or multiple cohort studies|
|D||Uncontrolled or observational studies only|
|Level of Evidence ||Effect||Change||Magnitude of Effect Size ||Scientific Consensus||Comments|
Appears to benefit the skin when topically applied as part of a cream
May induce hair growth when topically applied
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. It has a structure similar to Capsaicin and Synephrine, sharing a 1,3,7-cyclohexene group with a carbon tail.
It can naturally be found in many foods, most notably raspberries (in which case it is synthesized from coumaroyl-CoA) but also in Rheum officinale, however most raspberry ketone is synthesized or produced via bacteria due to its high demand in cosmetics and as a flavoring agent. Secondary to usage in food products, it has been estimated that dietary intake for an average human is around 0.42mg/kg bodyweight, consumed through processed foods containing this flavoring agent.
Raspberry ketones have a vaguely 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.
After oral ingestion, Raspberry ketones are targeted by sulfation and glucuronidation enzymes of the hepatic P450 enzyme system.
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). The main metabolite of raspberry ketones is urinary in nature, either the sulphate or glucuronide conjugate of said derivations.
Raspberry ketones have mixed evidence as to whether they can stimulate lipolysis as evidenced by glycerol release, with one study noting that 10µM tripled glycerol release while another (which noted the mechanism was via augmenting the effects of norepinephrine) failed to find an influence at 10µM and required 10mM. There is no detectable binding to β-adrenergic receptors.
Increased secretion and cellular levels of adiponectin were also noted after 4 days of incubation and has been noted to be somewhat preserved in a rat model of steatohepatitis which also benefitted leptin levels (averting the increase seen in the NAFLD control).
Appears to increase lipolysis via augmenting the effects of norepinephrine, but occurs at a very high cellular concentration and may not be practically relevant
Rats fed 0.5-2% raspberry ketones (total of the diet, is in the range of 0.545-2.18g/kg daily) during periods of high fat overfeeding noted dose-dependent anti-obese actions in preventing body weight gain, although the group fed 2% raspberry ketones still gained more weight than normal diet control.
Toxicological studies also noted decreases in body weight associated with raspberry ketones at 1% of the diet.
Currently, the one human study to investigated the effects of raspberry ketones (fat loss of 7.8% relative to the 2.8% in placebo; weight loss of 2% relative to 0.5% without detectable differences in caloric intake) was highly confounded in the formulation of METABO (raspberry ketones paired with Caffeine, Capsaicin, Garlic, Ginger and Citrus aurantium as a source of Synephrine) and the benefits cannot be traced back to raspberry ketones per se. This study also noted an elevated of serum leptin (no influence on resistin nor adiponectin) associated with intervention.
Limites human evidence is highly confounded and does not appear to support a role for raspberry ketones in isolation for inducing fat loss
In vitro studies with breast cancer cell lines suggest that Raspberry Ketones can inhibit the androgen receptor, with an IC50 value of 252uM.
The concentration of which blocking of the androgen receptor occurs is quite high, and not likely to be relevant following oral ingestion of standard (low) doses
A study conducted in rats noted that 1-2% of the diet as raspberry ketones was able to attenuate increases in liver fat associated with a high fat overfeeding diet, with the 2% group not being significantly different than control (control at 10.7+/-1.6mg/g triglycerides in the liver, high fat control at 35.6+/-6.8mg/g, and 2% raspberry ketones at 17.9+/-1.9mg/g). These doses were later tested in another rat model of steatohepatitis, and decreases in liver triglycerides and cholesterol was noted with normalization of serum HDL-C and LDL-C; liver enzymes were beneficially influenced, although to a more minor degree.
It is thought that this is due to a preservation of PPARα and LDL receptors in the livers of rats fed both raspberry ketones and an obesogenic diet.
May have some beneficial influences on liver fat buildup, but this is limited by both animal models (well characterized differences between animals and humans in regards to hepatic fatty acid metabolism) and the high dose of raspberry ketones used
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). 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.
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'. The ketones this list refers to are the raspberry ketones, most notably 4-(4-hydroxyphenyl)butan-2-one.
In regards to safety, a recent review suggested that not enough information exists to draw a conclusion due to small sample sizes.
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. In rats, intake of up to 100mg/kg bodyweight does not cause any short-term alterations in markers of blood health, and the LD50 is established at around 1.3-1.4g/kg bodyweight.
(Common misspellings for Raspberry Ketones include rasberry, razberry, ketone, respbarry, raspbary, rasbarri)
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