No replies to this topic

[tunt01]

Kroemer G, e. (2018). Carbotoxicity-Noxious Effects of Carbohydrates. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 6 November 2018, from https://www.ncbi.nlm.../?term=30340032

 

Kroemer G1, López-Otín C2, Madeo F3, de Cabo R4.

 

Modern nutrition is often characterized by the excessive intake of different types of carbohydrates ranging from digestible polysaccharides to refined sugars that collectively mediate noxious effects on human health, a phenomenon that we refer to as "carbotoxicity." Epidemiological and experimental evidence combined with clinical intervention trials underscore the negative impact of excessive carbohydrate uptake, as well as the beneficial effects of reducing carbs in the diet. We discuss the molecular, cellular, and neuroendocrine mechanisms that link exaggerated carbohydrate intake to disease and accelerated aging as we outline dietary and pharmacologic strategies to combat carbotoxicity.

 

 

 

MOA:

 

• GLYCOLYSIS:
  • the first steps of glycolysis are under feedback regulation inhibiting excessive glucose utilization,
• FRUCTOSE catabolism is unrestrained
  • allowing for limitless utilization of fructose carbons for gluconeogenesis, lactate production, acetyl-CoA synthesis, and consequent lipogenesis (Lim et al., 2010). Hence, fructose is highly lipogenic
  • magnified with saturated fat intake

 

 

KETOGENIC DIET

 

 

PHARMACOLOGICAL OPTIONS

 

ACARBOSE

• inhibits alpha-glucosidase an enzyme that reduces the breakdown of complex carbs
• acarbose effectiveness linked to shift in microbiome (Gu et al 2017)
• legumes contain natural inhibitors alpha-glucosidase and alpha-amylase

 

 

GLIFOZINS

• inhibits sodium/glucose cotransporter 2 (SGLT2)
  • prevents recover of glucose from kidney (ends up being urinated out)
  • dapaglifozin is anti-hypertensive, anti-diabetic

 

D-GLUCOSAMINE

• glycolysis inhibitor
• MOA (?)

 

METFORMIN

• Inhibits mitochondrial isoform of GDPH
  • GDPH catalyzes conversion of of G3P to DHAP
    • inhibition blocks gluconeogenesis
  • GDPH KO mice re-capitulate the effects of metformin
  • Metformin is not a Complex I inhibitor, so much as it is actually a GDPH inhibitor that localizes in the liver (see Madiraju, Shulman, et al 2014, 2018)

 

"tempting to speculate that metformin inhibits the accumulation of AGEs due to its capacity to inhibit GPDH and hence to deplete DHAP as well as methylglyoxal, an effect that has been observed in diabetic patients (Beisswenger et al., 1999). However, metformin has also been shown to increase the expression and activity of the enzyme that detoxifies methylglyoxal, which is glyoxalase 1 (Glo1) (Kender et al., 2014)"

 

Edited by tunt01, 06 November 2018 - 05:05 PM.