Episode 13 – What happens to fructose-fed monkeys?

Short summary: In episode 13 Gabor and I review a 2011 study looking at the metabolic consequences of rhesus monkeys being fed a grain-based diet supplemented with 500mL of fructose loaded Kool-Aid a day over a year.

Show notes:

  • The study: Fructose-Fed Rhesus Monkeys: A Nonhuman Primate Model of Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes (Bremer et al. 2001)
  • Gabor explains what is fructose, glucose and high-fructose corn syrup (HFCS)
  • Gabor explains the enzymatic means by which HFCS is made
  • Absorbed fructose is extracted by, held, and processed in the liver, with little fructose circulating in the blood stream or delivered to peripheral tissues“ – PMC
  • Absorbed glucose or that produced in the liver from fructose or other precursors is either metabolized in the liver or exported to the blood stream and further to extrahepatic tissues“ – PMC
  • We talk about what this study is and isn’t.
    • What it is: the study “permits comparative studies with humans and the direct linkage of genotype with phenotype (insulin deficient and hyperglycemic insulin sufficient and normoglycemic)” – Bremer et al. 2011
  • What it isn’t: “This study doesn’t tell us much about the lasting effects of low fat real food” – Gabor
    • Is it useful to interpret data about other low fat studies? “Those diets, including the rice and orange juice Kempner, are well below 10 % fat. I’m not a low fat diet proponent, but this study was not designed to assess the effect of macronutrients. The regular monkey chow just happens to be low fat” – Gabor
  • What about the lack of non-sweet drink control monkeys?
    • “This considered in the paper. Basically most monkeys not included in such trials (mostly females though) are free of MetSyn and diabetes” – Gabor
  • Why isn’t this study more widely known? Shouldn’t we be more confident about advice to reduce total fructose according to its findings?
    • “It’s explained away with other, less relevant studies, e.g. short human studies with poor control, rodent studies, etc” – Gabor
  • The animals showed a progressive decrease in fat oxidation throughout the study period
    • “Yes, but they were not eating more ‘calories’” – Gabor
  • The monkey’s body composition changed for the worse over the course of 12 months. This was not due to ‘overeating’, as the common misinterpretation suggests

Agenda

Fructose-Fed Rhesus Monkeys: A Nonhuman Primate Model of Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes (Bremer et al. [2011] https://www.ncbi.nlm.nih.gov/pubmed/21884510)

  • What is fructose? What’s HFCS? How’s it made?
    • Absorbed fructose is extracted by, held, and processed in the liver, with little fructose circulating in the blood stream or delivered to peripheral tissues“ – PMC
    • Absorbed glucose or that produced in the liver from fructose or other precursors is either metabolized in the liver or exported to the blood stream and further to extrahepatic tissues“ – PMC
  • Adiponectin + HMW adiponectin decreased whilst monkeys gained weight
    • “identification of adiponectin receptor agonists that bear promise as therapeutic insulin sensitizers” – Wiki
    • coronary artery diseasehas been found to be positively associated with high molecular weight adiponectin, but not with low molecular weight adiponectin” -Wiki
  • “this model permits comparative studies with humans and the direct linkage of genotype with phenotype (insulin deficient and hyperglycemic insulin sufficient and normoglycemic)” – study

Gabor

  • “This study doesn’t tell us much about the lasting effects of low fat real food”
  • “Those diets, including the rice and orange juice Kempner, are well below 10 % fat. I’m not a low fat diet proponent, but this study was not designed to assess the effect of macronutrients. The regular monkey chow just happens to be low fat”
  • “This [lack of non-sweet drink controls] is considered in the paper. Basically most monkeys not included in such trials (mostly females though) are free of MetSyn and diabetes”
    • [would these monkeys eat the same diet (apart from the Koolaid)?] “I don’t know. I guess it depends on the price of standardized chows”
  • [Pretty conclusive, good find but why oh why is compelling evidence such as this not gained any public attention/traction? It’s 6 years old!!] “It’s explained away with other, less relevant studies, e.g. short human studies with poor control, rodent studies, etc”
  • [the animals showed a progressive decrease in fat oxidation throughout the study period” “Yes, but they were not eating more ‘calories’”
    • [They used less energy too with time, got “fat and lazy” ?] “Exactly. Their body composition changed for the worse. A lot worse, but not due to ‘overeating’ as it’s commonly interpreted”

3 comments On Episode 13 – What happens to fructose-fed monkeys?

  • Hi Raphi and Gabor,

    Well done on the podcast! I really appreciate the two of you taking the time to do these podcasts, and I commend you on your analysis! Towards the end of the podcast, Gabor was theorizing on how fructose could contribute to adipocyte hypertrophy by blocking adipocyte differentiation. I understand adipocytes have GLUT 5 receptors and that in vitro studies have shown fructose has effects on adipocytes. However, I was wondering how much fructose is able to make it past the liver and reach adipocytes in vivo? I tried doing a quick literature search but have come up short so far. Maybe you have seen some literature on this before?

    • Hi Justin,

      thanks for the kind words, it’s really appreciated. I don’t know what’s the concentration range for fructose at the adipocyte in vivo. It’s also not clear how fructose exerts its effects, whether directly at the adipocyte or by recruiting additional factors from other tissues (e.g. liver).

      if i come across some data to answer your question i’ll share it here. please do the same 🙂

      • After quite a bit of looking, I found this paper “Fructose metabolism in humans – what isotopic tracer studies tell us”. It states “After 50–150 gm fructose ingestion, the peak of fructose concentration in plasma would be between 3–11 mg/dL.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533803/

        I think Gabor has seen this paper before because he said something similar when I asked him.

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