LeuSynergy™

LeuSynergy™

An exercise and caloric restriction mimetic that works on NAD+ efficiency and sirt1 activation. This low-dose leucine compound is best known for its incredible enhancement of weight loss with GLP 1’s like semaglutide.
LeuSynergy + GLP-1s has become a foundational protocol for weight loss and metabolism optimization.

SUBSCRIPTION PRICE
DETAILS
SUPPLEMENT FACTS

Per Bottle
120 capsules
Serving Size
2
Directions
2 capsules in the morning and 2 capsules 90 minutes after lunch.

Amount per serving

L-Leucine

1100mg t

Vitamin B6 (as Pyridoxal 5 Phosphate)

15mg t

Resveratrol (from Polygonum Cuspidatum Extract) (NLT 98% Resveratrol)

50mg t

† Daily Value (DV) not established 
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Cellular Pathways 

Delivering the right dose of Leucine decreases the amount of NAD needed to activate SIRT-1

Leucine at a concentration of 0.5mM was shown to decrease the kM of NAD by 50%.

With Leucine, LESS NAD+ is needed for SIRT-1 functions, improving NAD+ utilization in other cellular pathways.

Why this matters:

SIRT-1 Downstream Effects

Stimulates caloric restriction and exercise pathways through these gene transcription factors:

PGC-1a

The core regulator of mitochondrial biogenesis

PPAR

Regulate fat oxidation

AMPK

Master regulator of cell energy

NF-kB

Inhibition leads to decreased inflammation and oxidative stress 

Clinical Studies

Leucine-Resveratrol Synergy

Human Pre-diabetic
Subjects Randomized:

Leucine 1.1 g + Resveratrol 50mg Twice Daily vs. Placebo

  • OGTT and 60 min glucose and insulin concentration
  • Reduced insulin resistance by 33%
  • Significant improvement and insulin/glucose dynamics

* Lipps J, Hagan S, Clark M, Davis D, Stone L, Survant L, et al.: Resveratrol synergy in pre-diabetes. Diabetes 2013;62: Poster 78-LB

Weight Loss – Fat Oxidation – Insulin Sensitivity

Synergy with GLP-1s

Semaglutide, Tirzepatide, Liraglutide
Studies show 15% reduction in body weight when semaglutide was accompanied by caloric restriction and exercise. Using an exercise mimetic like LeuSynergy is foundational in weight loss and metabolic health outcomes.

Insulin Independent Pathways for Glucose Disposal

GLP-1
Increase in GLUT4 expression by activating AMPK

SIRT-1
Increase in GLUT4 expression through SIRT1 deacetylation of PGC-1a

Improved Fat Oxidation

GLP-1
Direct effects on hepatocytes by activating genes involved in beta-oxidation of fatty acids

SIRT-1
Activation of PGC-1a and PPAR resulting in an increase in fatty acid oxidation and oxidative phosphorylationn

Oxidative Stress and Pancreatic Beta Cell Protection

GLP-1

Reduced oxidative stress in pancreatic islets. Increases B-cell mass by regulating cell kinetics and suppressing oxidative and ER stress, and amerlioration of glucolipotoxicity.

SIRT-1

SIRT-1 deacetylation and inhibition of NF-kB protecting beta cells from oxidative stress and inflammatory cytokines.

References

  1. Zemel MB. Modulation of Energy Sensing by Leucine Synergy with Natural Sirtuin Activators: Effects on Health Span. J Med Food. 2020 Nov;23(11):1129-1135. doi: 10.1089/jmf.2020.0105. Epub 2020 Aug 4. PMID: 32758058.
  2. Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013;123(7):2764-2772. doi:10.1172/JCI67227
  3. Lan F, Weikel KA, Cacicedo JM, Ido Y. Resveratrol-Induced AMP-Activated Protein Kinase Activation Is Cell-Type Dependent: Lessons from Basic Research for Clinical Application. Nutrients. 2017 Jul 14;9(7):751. doi:10.3390/nu9070751. PMID: 28708087; PMCID: PMC5537865.
  4. Kitada M, Ogura Y, Monno I, Koya D. Sirtuins and Type 2 Diabetes: Role in Inflammation, Oxidative Stress, and Mitochondrial Function. Front Endocrinol (Lausanne). 2019;10:187. Published 2019 Mar 27. doi:10.3389/fen-do.2019.00187
  5. Iside C, Scafuro M, Nebbioso A, Altucci L. SIRT1 Activation by Natural Phytochemicals: An Overview. Front Pharmacol. 2020;11:1225. Published 2020 Aug 7. doi:10.3389/fphar.2020.012