Resveratrol-leucine combo boosts fat burning

A cocktail of resveratrol and leucine can help you lose weight faster. Nutritionists at the University of Tennessee write in Nutrition and Metabolism that this combination boosts fat and glucose burning in cells. A combination of resveratrol and HMB works just as well.

The amino acid leucine and its metabolite HMB not only stimulate the production of muscle fibre, they also reduce fat mass. This is probably because both compounds enhance the activity of the enzyme Sirt1. [Am J Physiol Endocrinol Metab. 2012 Nov 15; 303(10): E1234-44.] [FASEB Journal. 2012; 26:251.6.]

Sirt1 is an enzyme in the nuclei that enables cells to repair themselves. It also activates anti-cancer genes like p53. The more active Sirt1 is, the less room for manoeuvre free radicals have.

Sirt1 has a little brother, Sirt3, which is present outside the cell nuclei, in the cytoplasm. Sirt1 and Sirt3 play a key role in energy metabolism. They are involved in the production of mitochondria, which enable cells to burn glucose and fatty acids, thus generating more energy. Sirt1 becomes more active the less energy you consume, but also if you consume substances like resveratrol.

The effect of leucine on Sirt1/3 is limited. And in complex organisms the effect of resveratrol is also limited. The researchers wondered whether a combination of the two compounds would have a mutually strengthening effect.

The researchers did experiments with mice that had been fattened for 6 weeks first. The animals were then given food for another six weeks, which had been enriched with nothing [the control group], resveratrol, leucine, HMB or combinations of these.

At the end of the experiment the animals in a resveratrol-leucine group had 35 less fat that the mice in the control group, as you can see in this table. The mice that had only been given resveratrol – albeit a high dose – had only 8 percent less fat than the mice in the control group.

Below you can see how the combination of leucine/HMB and resveratrol boosted the burning of fatty acids in the mice’s cells. The second and third figures below show how the combination led to an increase of Sirt1 and Sirt3 respectively in the muscle cells.




Exposure to leucine and resveratrol boosted the activity of the enzyme AMPK in the mouse cells, as you can see in the figure above.

In the animals that had been given both leucine/HMB and resveratrol, the insulin level went down and the muscle cells’ glucose uptake increased. [Table]

At the end of the supplementation period the researchers gave their lab animals labelled palmitate [a fatty acid] and a labelled glucose analogue. In the photos below you can see that the mice’s tissues absorbed more fatty acids and glucose as a result of the HMB/resveratrol combination.


Converting the doses used to human equivalents you arrive for the ‘low’ resveratrol groups at a couple of dozen milligrams resveratrol per day. The leucine dose used converts to a couple of dozen grams per day. The human equivalent of the quantity of HMB used in the ‘low’ HMB groups amounts to several grams per day.

Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice.

Bruckbauer A, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JS.


NuSirt Sciences Inc, 11020 Solway School Rd, Knoxville, TN, 37931, USA. mzemel@nusirt.com.



Sirtuins are important regulators of glucose and fat metabolism, and sirtuin activation has been proposed as a therapeutic target for insulin resistance and diabetes. We have shown leucine to increase mitochondrial biogenesis and fat oxidation via Sirt1 dependent pathways. Resveratrol is a widely recognized activator of Sirt; however, the biologically-effective high concentrations used in cell and animal studies are generally impractical or difficult to achieve in humans. Accordingly, we sought to determine whether leucine would exhibit synergy with low levels of resveratrol on sirtuin-dependent outcomes in adipocytes and in diet-induced obese (DIO) mice.

3T3-L1 mouse adipocytes were treated with Leucine (0.5 mM), ?-hydroxy-?-methyl butyrate (HMB) (5 ?M) or Resveratrol (200 nM) alone or in combination. In addition, diet-induced obese mice were treated for 6-weeks with low (2 g/kg diet) or high (10 g/kg diet) dose HMB, Leucine (24 g/kg diet; 200% of normal level) or low (12.5 mg/kg diet) or high (225 mg/kg diet) dose resveratrol, alone or as combination with leucine-resveratrol or HMB-resveratrol.

Fatty acid oxidation, AMPK, Sirt1 and Sirt3 activity in 3T3-L1 adipocytes and in muscle cells, were significantly increased by the combinations compared to the individual treatments. Similarly, 6-week feeding of low-dose resveratrol combined with either leucine or its metabolite HMB to DIO mice increased adipose Sirt1 activity, muscle glucose and palmitate uptake (measured via PET/CT), insulin sensitivity (HOMAIR), improved inflammatory stress biomarkers (CRP, IL-6, MCP-1, adiponectin) and reduced adiposity comparable to the effects of high dose resveratrol, while low-dose resveratrol exerted no independent effect.

These data demonstrate that either leucine or its metabolite HMB may be combined with a low concentration of resveratrol to exert synergistic effects on Sirt1-dependent outcomes; this may result in more practical dosing of resveratrol in the management of obesity, insulin-resistance and diabetes.

PMID: 22913271 [PubMed] PMCID: PMC3506499

Source: http://www.ncbi.nlm.nih.gov/pubmed/22913271

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