Paper in Cell Metabolism:

Fatty Acid Metabolites Combine with Reduced β Oxidation to Activate Th17 Inflammation in Human Type 2 Diabetes

It’s long been known that both “lipotoxicity” and “glucotoxicity” are associated with inflammation leading to diabetes. But it wasn’t clear which, when, and how, resulting in different factions battling for supremacy. The science of this controversy is now beginning to come into focus.

A paper two weeks ago from Softic et al. in Cell Metabolism demonstrates that fructose inhibits mitochondrial beta-oxidation through alteration of specific mitrochondrial proteins, conversely glucose stimulates it. Thus dietary sugar is more metabolically problematic than dietary starch; a finding that our group corroborated in obese children.

This paper from Nicholas et al. also in Cell Metabolism, demonstrates that because of that mitochondrial dysfunction, fatty-acylcarnitine, which should be beta-oxidized, can power the production of TH17 cytokines that in part drive that inflammation. Furthermore, one must remember that some of that fatty acid production can be derived via de novo lipogenesis using fructose as a substrate.

This paper, combined with Softic, helps bridge the gap to show that, at the molecular level, it appears to be the combination of both fat and fructose at the mitochondria that drives the inflammatory process.

The Societal Math of Processed Food (U.S.)

The food industry grosses 1.46 Trillion / yr
-657 billion is gross profit

Health care costs in the U.S. total $3.5 trillion / yr
-75% of which is chronic metabolic disease
-75% of which is preventable

Thus, $1.9 trillion / yr is wasted.

We lose triple what the food industry makes.

This is unsustainable, and explains why Medicare will be broke by 2026, and neither “Obamacare” or “Trumpcare” or “Medicare for All” can fix it (and not the NHS either).

This paper is huge. One of the arguments the food industry advances is that sugar consumption has gone down while obesity has gone up, so it can’t be sugar. This paper uses a complex statistical analysis to show that US obesity is a function of both current sugar consumption and an derivative of the sugar consumed by the previous generation going forward. In other words, it’s the economic equivalent of “epigenetics”. This is yet another nail in the coffin (as if we needed any more nails)!

U.S. obesity as delayed effect of excess sugar

https://www.sciencedirect.com/science/article/pii/S1570677X19301364

“The majority of observational studies addressing synthetic or non-nutritive sweeteners (NNS) consumption show an association with metabolic dysregulation.”

Beyond food intake, numerous studies have shown…

animals consuming synthetic sweeteners exhibit weight gain
Feijó et al., 2013
Swithers and Davidson, 2008
Swithers et al., 2010
Swithers et al., 2013

impaired glucose homeostasis
Suez et al., 2014
Swithers et al., 2012

weaker caloric compensation
Swithers et al., 2010

synthetic sweeteners act through the microbiome
Suez et al., 2014

reduced validity of “sweetness” to predict caloric content
Swithers et al., 2010

significant correlation between NNS consumption and weight gain in an 80,000 participants study
Stellman and Garfinkel, 1988

Other independent studies confirmed these associations, with synthetically sweetened beverage consumption being associated with a much higher incidence of metabolic syndrome (odds ratio ∼1.93) when compared to non-users
Fowler et al., 2008
Lutsey et al., 2008

and NNS consumption has been identified as a significant risk factor for metabolic disease

in children
Blum et al., 2005

in middle-aged adults
Dhingra et al., 2007

and in the elderly
Fowler et al., 2015

One study showed that NNS consumers exhibit reduced weight gain
Schulze et al., 2004

however, these participants showed increased risk for developing diabetes in an 8-year follow-up.

Furthermore, human intervention studies have also shown that ingestion of NNS could

enhance appetite
Blundell and Hill, 1986
Rogers and Blundell, 1989

promote hunger
Tordoff and Alleva, 1990

and increase food consumption
Lavin et al., 1997
Rogers and Blundell, 1989
Tordoff and Friedman, 1989a

resulting in impaired glucose tolerance
Pepino et al., 2013
Suez et al., 2014

However, other studies have reported no major effect or weight loss as a result of consuming NNSs
De La Hunty et al., 2006
de Ruyter et al., 2012
Raben et al., 200

The overall impact of NNS on metabolic health remains controversial.

“Despite inclusion in thousands of products, and consumption by billions of people, the molecular effects of ingesting synthetically sweetened food are not well understood. Moreover, there is conflicting evidence from both human and animal studies as to whether or not synthetic sweeteners interact with overall physiology or regulation of energy homeostasis.”

Excerpts from: Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response

All the studies referenced here are cited and hyperlinked in the article.