Two 2022 papers from a clinical trial investigating dietary AGEs’ effects in middle-age people:

“A 4-week diet low or high in AGEs has no effect on insulin sensitivity, secretion, or clearance; vascular function; or overall inflammation in abdominally obese but healthy individuals. These findings require validation in large prospective cohort studies and in populations with established disease such as diabetes and kidney failure.

Our broad array of null findings are not in agreement with those of previous animal and human studies. In mice, baked chow diets high in AGEs led to impaired insulin secretion, insulin resistance and T2DM, and arterial stiffness.

However, usage of baked chow diets may have led to other effects than solely increasing dietary AGEs, such as decreased vitamin bioavailability and increased acrylamide formation. Additionally, AGE levels in baked chow may be higher than those in human food.

The present study has several potential limitations. Most importantly, because of the relatively short intervention duration of 4 weeks, we are unable to draw conclusions on longer-term effects of a diet low or high in AGEs.”

https://insight.jci.org/articles/view/156950 “A 4-week high-AGE diet does not impair glucose metabolism and vascular function in obese individuals”

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A second paper investigated the trial’s gut microbiota changes:

“A 4-week diet low or high in AGEs has a limited impact on gut microbial composition of abdominally obese humans, paralleling its previously observed limited biological consequences. In contrast, habitual intake of dicarbonyls, reactive precursors of AGEs, was associated with both lower and higher abundances of several genera.

We cannot exclude the possibility that increased intake of dicarbonyls in the high-AGE group influenced our results. Although we observed very limited effects of intervention diets on our outcomes overall, there was an increase in plasma adiponectin after high- compared to low-AGE diet.

Potentially, this was a result of increased intake of dicarbonyls rather than AGEs. Interestingly, most associations between habitual intake of dicarbonyls and genera abundance were not shared between individual dicarbonyls, suggesting unique relationships.

Limitations of our trial:

• A 4-week diet may be too short to result in changes in the gut microbial composition;
• Analysis of 16S rRNA instead of metagenomics sequencing;
• Focus on markers based on relative abundance instead of absolute abundance;
• It is possible that any beneficial effects of the low-AGE diet on insulin sensitivity were counteracted by less favorable effects on the gut microbiota, ultimately leading to no change in insulin sensitivity after the low- versus the high-AGE diet;
• We did not measure short and branched chain fatty acids, which could have provided more insight into biological relevance of these associations as well as changes in genera abundance after the low- and high-AGE diets;
• Regarding estimations of habitual dicarbonyl intake, FFQs may be prone to recall bias, and no FFQ so far has been validated for estimating dicarbonyl intake; and
• Low- and high-AGE diets were not matched for their glycemic load and index, and these factors may influence endogenous formation of AGEs.”

https://www.mdpi.com/1422-0067/23/10/5328/htm “A 4-Week Diet Low or High in Advanced Glycation Endproducts Has Limited Impact on Gut Microbial Composition in Abdominally Obese Individuals: The deAGEing Trial”

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Some previous curations explored topics related to these papers:

• All about AGEs stated: “AGEs and their precursors cannot be grouped together. Specific, individual information is required for a proper evaluation.”
• Resistant starch therapy stated: “Microbiome sequencing data are compositional, meaning that gene amplicon read counts do not necessarily reflect bacterial absolute abundances. Instead, read counts are typically normalized to sum to 100%. For this reason, relative abundances of smaller keystone communities (e.g. primary degraders) may increase, but appear to decrease simply because cross-feeders increase in relative abundance to a greater extent. These limitations illustrate the necessity of sufficiently powering RS interventions where microbiome composition is the primary endpoint, collecting critical baseline data and employing appropriate statistical techniques.”
• Rodent studies mentioned in Caloric restriction’s epigenetic effects and Effects of advanced glycation end products on quality of life and lifespan relied on AGEs in baked chow diets for their findings; and
• Nano-sulforaphane vs. barbecue chemicals stated: “Women at the early stage of pregnancy should avoid barbecue.”

Happy Independence Day!