How To Have Your Cake And Eat It Too: Calorie Restriction And Fasting Mimetics

Calorie Restriction Mimetics (CRMs) are compounds that can induce the same mechanisms as eating less, without having to actually eat less. R

In this, post we will discuss how to have your cake (food) and eat it too.. 

What Defines A CRM?

CRMs should: R

1. Mimic the metabolic, hormonal and physiological effects of CR
2. Don't significantly decrease long-term food intake
3. Activate stress–response pathways, as observed in CR, and protect against a variety of stressors
4. Reduce inflammation and autoimmunity. 

Mimicking CR/Fasting may improve:

1. Adaptability to Stress (CR acts on hormesis via NRF2) R R R
2. Autophagy (improve stem cells) R R R R
3. Body Fat Mass R R
4. Cardiovasuclar Function R R R 
5. Eyesight/Ocular Health R R
6. Healthspan R R
7. Immune Function R
8. Insulin Sensitivity R R
9. Kidney Function R
10. Leptin Sensitivity R
11. Lifespan R
12. Liver Function R
13. Memory (is Alzheimer's) R
14. Metabolism (may help with hypoxia) R R
15. Mitochondrial Function R
16. Muscle R
17. NAD levels R R
18. Neurogenesis R
19. Prevention of Cancer and Anti-tumor Efficacy (of chemotherapy) R R R R
20. Skin and Wound Healing R

Some CRM's can mimic exercise or even synergize well with exercise and improve muscle function. R R

Compared to the rest of the Japanese population, inhabitants of Okinawa who followed a low-calorie diet over a prolonged period of time show to have a longer lifespan and an increased healthspan. R

They eat a mildly caloric restricted diet (10-15%) and high consumption of foods that may mimic the biological effects of caloric restriction, including sweet potatoes, marine-based carotenoid-rich foods, and turmeric. R

These CRMs work on the mechanisms of calorie restriction.

Dietary/Mechanical Strategies (that aren't calorie restriction):

• Amino Acid Restriction R
• Avocado (Mannoheptulose) R
• Bariatric Surgery R
• Cinnamon (Methylhydroxychalones) R
• Coffee R
• Intermittent Fasting/Feeding R
• Olive Oil (Tyrosol) R
• Rosemary (Rosmarinic Acid) R
• Sesame (Sesamin) R
• Tomatoes (Tomatidine) R
• Turmeric (Curcumin) R

Supplements:

• Allantoin R
• Allulose R
• Ashwaganda (Withaferin A) R
• Astaxanthin R
• BCAAs (Leucine can increase mitochondrial mass in human muscle cells) R R
• Caffeic acid R
• Caffeine R
• Carnitine R
• Chitosan (Inhibiting Nutrient Absorption) R
• EGCG R R
• Fisetin R R
• Ginseng (Ginsenosides) R
• Glucosamine R
• Gymnema R
• Gynostemma (jiaogulan)
• Hesperidin R
• Kaempferol R
• Ketones R
• Kokum (Garcinia Indica) R
• Lactoferrin R
• Licorice (isoliquiritigenin) R 
• Lipoic Acid (weak) R
• Mannan Oligosaccharides (Inhibiting Nutrient Absorption) R
• MitoQ R
• NAC R
• Naringenin R
• Nicotinamide Riboside R
• Olestra R
• Polydatin R
• Quercetin R
• Resveratrol R
• Thundergod Vine (Celastrol) R
• Ursolic acid (ie holy basil, thyme, rosemary) R

Hormones:

• Adiponectin (binding to AdipoR1 and AdipoR2)
• Irisin R
• Leptin (possibly lower) R
• Melatonin R
• Meteorin-like R
• NPY R
• Resistin (lower levels) R

Drugs:

• Acarbose (Inhibiting Nutrient Absorption) R
• Allantoin R
• AICAR R
• Aspirin R
• Bezafibrate R
• Dapsone R
• Epitalon R
• Exanadin
• GW1516 R
• Hydroxycitrate (citric acid) R
• LY‐294002 R
• Metformin R R
• Olbetam (niacin derivative)
• Orlistat (Inhibiting Nutrient Absorption) R
• Oxaloacetic acid R
• Pioglitazone R
• Rapamycin R
• Rimonabant
• Rosiglitazone (modulation PPARs leptin/adiponectin)
• SARMs (some) R
• Sodium phenylbutyrate
• Spermidine R
• SRT1720 R
• Trichostatin A (TSA) R

Exercise Mimetics may go well with CRMs. 

Some Mechanisms / Pathways Of CR Mimetics

Working on these mechanisms may also help mimic CR:

• Increasing AMPK R R
• Increasing cAMP R
• Increasing ERRγ R
• Increasing FGF21 R R
• Increasing FOXO R
• Increasing HSF1 R
• Increasing LKB1 R
• Increasing NO -> HSP R
• Increasing NRF1 R
• Increasing NRF2 R
• Increasing NR3C4 R
• Increasing PNC-1 R
• Increasing PPARβ/δ R R
• Increasing PGC-1α R
• Increasing REV-ERBα R
• Increasing SIRTs (and other STACs, ie fisetin) R R
• Increasing SOD R
• Increasing UCP2 and UCP3 R
• Inhibiting ActRIIB R
• Inhibiting DPP-4
• Inhibiting Glycolysis R
• Inhibiting HDACs 1 and 2 R
• Inhibiting mTOR R R
• Inhibiting Myostatin R
• Reduces AGEs R
• Reduces FAO R
• Reduces GH R
• Reduces HMG-Co-A reductase R
• Reduces IGF1 R

Advanced:

• Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins (3 ways). R R
  1. The depletion of cytosolic AcCoA by interfering with its biosynthesis
  2. The inhibition of acetyltransferases, which are enzymes that transfer acetyl groups from AcCoA to other molecules, mostly leucine residues in cellular proteins
  3. The stimulation of deacetylases, which catalyze the removal of acetyl groups from leucine residues. 
• CRMs deplete regulatory T Cells from tumor bed and trigger an autophagy-dependent anticancer immune response. R
• In the liver, AdipoR1 activates the AMPK pathways and AdipoR2 activates PPARα pathways. R
• AMPK enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets such as PPARγ coactivator 1α (PGC-1α) and forkhead box O1 (FoxO1), and is regulated by adiponectin–adipoR1 system. R
• CR induces the function of the pyrazinamidase/nicotinamidase 1 (PNC-1) enzyme which deaminates and depletes nicotinamide. R