Re: Jeff Nippard- "Sugar Myth Busted" Video

Hey everyone,   A kind twitter user just asked me for my thoughts on this video:  https://www.youtube.com/watch?v=9JrT84PeTgw By Jeff Nippard.     (Before I continue just want to say I don't intend to encourage any contempt for Jeff himself, I have enjoyed some of his other videos and he seems like he genuinely wants to help people. Just pointing out that his stance on this particular topic is drastically lacking in information.)   

The video basically points out a couple studies for and against Sugar consumption leading to increased weight gain, then wraps it up with "Correlation does not equals causation"

What I would have liked to see is him addressing some of the physiological reactions to the consumption of sugar (fructose). Or, at least, one of these: 

Fructose enhances weight gain by
■Lowering energy expenditure
-Fructose is the only carbohydrate that depletes energy in the cell before it makes energy.  In the mitochondria, all nutrients produce energy in the form of ATP- the "energy currency" that we use to drive all our biological processes. There is a measurable fall in ATP in a human when delivered fructose intravenously and orally (via soft drink). [Fructose gets metabolized by an enzyme called fructokinase and that phosphorylates fructose to fructose-1-phosphate and in that process, ATP gets consumed.] 

-Having less ATP by itself should be alarming for us, but this drastic drop in ATP acts as, as Prof. Richard Johnson puts it, a "mayday signal" in the cell. This causes inflammation, oxidative stress and an arrest in protein synthesis. (Particularly bad if you want to gain muscle)
Relevant snippet from John Yudkin's "Pure, White and deadly" [pg 139]: "One of the unexpected effects that we found when putting sugar into the diet was that it interferes with the body's use of protein in the diet. We first noticed this when we fed our rats a diet that was low, but usually adequate, in protein. When fed on our normal diet with starch the rats grew perfectly well, but when we replaced the starch with sugar their growth was retarded. Looking more closely at the reason for this, we found that the sugar interfered with the body's use of protein, so that the rats lost protein instead of accumulating it as they should when growing." (I'm curious to know if Jeff got the chance to read the book)

■Stimulating insulin resistance
-During fructose metabolism, insulin receptor IRS-1 is serine phosphorylated, and serine IRS-1 is inactive. This insulin receptor being inactive means insulin can't do its job, contributing to insulin resistance. 

■Directly enhancing propensity for fat generation
-Fructose metabolism stimulates the production of Xylulose-5-Phosphate, which stimulates PP2A which activates ChREBP which then activates the three de novo lipogenesis ("new fat making") enzymes- ACL, ACC, FAS. 

-An increase in activity of another enzyme, "pyruvate kinase," which is important in the production of fat in the body from a variety of diet derived substances, is taken as measure of the fat forming activity of the liver. Rats given sucrose showed, after ten days, five times as much of this enzyme activity compared to rats without sucrose. 

-Through the action of AMP deaminase, fructose metabolism creates uric acid. This leads to several problems - gout and hypertension being two, increased fat production being another. This study (titled "Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress") in the Journal of Biological Chemistry found that if you put uric acid on liver cells, they will begin to produce fat. The way this works is: uric acid induces oxidative stress in the cells’ mitochondria. This specifically inhibits an enzyme called Aconitase in the citric acid cycle, leading a build up of citrate. (Citrate being a substance that stimulates fat production.) Uric acid also inhibits another enzyme required for the burning of fatty acids, leading to less ridding of fat and less ATP being produced. 

■Altering gut microbiome -I've read about this in a couple different studies and books. Pretty sure David Perlmutter's grain brain discusses fructose's effects on the gut microbiome.  Haven't gotten past the paywall, but this study seems to explore it: "Evidence is presented suggesting these sugar compounds, particularly fructose, condition the microbiota, resulting in acquisition of a westernized microbiome with altered metabolic capacity." Maybe you came across something during research for your microbiome vid?

■Makes people eat more
-Sucrose is addicting similar to the way a drug is addicting. Snippet from study Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake:  "Four components of addiction are analyzed. “Bingeing”, “withdrawal”, “craving” and cross-sensitization are each given operational definitions and demonstrated behaviorally with sugar bingeing as the reinforcer. These behaviors are then related to neurochemical changes in the brain that also occur with addictive drugs. Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin mRNA expression and dopamine and acetylcholine release in the nucleus accumbens. The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent. This may translate to some human conditions as suggested by the literature on eating disorders and obesity."

-Inhibits leptin signaling, making you "think" you're hungrier than you should be. As per "Toward a unifying hypothesis of metabolic syndrome." Fructose induces substrate-dependent phosphate depletion, which increases uric acid and contributes to hypertension through inhibition of endothelial nitric oxide synthase and reduction of NO; DNL and dyslipidemia; hepatic lipid droplet formation and steatosis; muscle IR; JNK-1 activation, contributing to hepatic IR, which promotes hyperinsulinemia and influences substrate deposition into fat; and CNS hyperinsulinemia, which antagonizes central leptin signaling and promotes continued energy intake. "

-I've also read that alterations to the microbiome enhances sugar/refined carbohydrate cravings (Need to dig around for something properly explaining this)

●Two relevant talks: 
Robert Lustig's Sugar: The Bitter Truth |Richard Johnson' Sugar and its Role in Driving Obesity and Fatty Liver
●Relevant Books:
Robert Lustig "Fat Chance" | Richard Johnson "The Fat Switch" | Gary Taubes "The Case Against Sugar" | John Yudkin "Pure, White and Deadly"