Wikipedia is a poor source of information on advanced glycation end products (AGEs)

A link to Wikipedia is usually on the first page of search results. The Wikipedia post on AGEs lacks the evidence that a reader may infer from its text.

For example, the second paragraph of the AGEs post, Dietary Sources, contained the following text and references:

  1. “However, only low molecular weight AGEs are absorbed through diet, and vegetarians have been found to have higher concentrations of overall AGEs compared to non-vegetarians. [4]
  2. Therefore it is unclear whether dietary AGEs contribute to disease and aging, or whether only endogenous AGEs (those produced in the body) matter. [5]
  3. This does not free diet from potentially negatively influencing AGE, but implicates dietary AGE may be less important than other aspects of diet that lead to elevated blood sugar levels and formation of AGEs. [4] [5]”

[4] https://www.sciencedirect.com/science/article/pii/S0278691513004444 “Advanced glycation end products in food and their effects on health” (not freely available) 2013 Denmark.

Please note on this linked page that a German researcher took the time to correct one bias of the Danish reviewers, citing evidence from his studies that:

“The deleterious effects of food-derived AGEs in subjects with type 2 diabetes mellitus are proven.”

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257625 “Dietary Advanced Glycation End Products and Aging” 2010 US.


Both of these references were reviews.

Unlike study researchers, reviewers aren’t bound to demonstrate evidence from tested hypotheses. Reviewers are free to:

  • Express their beliefs as facts;
  • Over/under emphasize study limitations; and
  • Disregard and misrepresent evidence as they see fit.

Reviewers also aren’t obligated to make post-publication corrections for their errors and distortions. For example, the Danes didn’t correct their review with any findings the German researcher presented.

As such, reviews can’t be cited for reliable evidence.


A sample of other problems with each of the Wikipedia sentences:

1. “However, only low molecular weight AGEs are absorbed through diet, and vegetarians have been found to have higher concentrations of overall AGEs compared to non-vegetarians. [4]”

The first part of sentence 1 came from the review’s abstract:

“Only LMW AGEs..may be absorbed from the gut and contribute to the body burden of AGEs.”

But the reviewers didn’t support their abstract’s statement with direct evidence from any study!

2. “Therefore it is unclear whether dietary AGEs contribute to disease and aging, or whether only endogenous AGEs (those produced in the body) matter. [5]”

The “therefore” of sentence 2 was misplaced. Sentence 1 didn’t attempt to explain whether “dietary AGEs contribute to disease and aging” or “only endogenous AGEs matter.”

Since sentence 2 wasn’t a consequence of sentence 1, the Wikipedia contributor(s) needed to support sentence 2 with evidence. Citing an “unclear” 2010 reference [5] ignored dozens of studies that provided better clarity.

3. “This does not free diet from potentially negatively influencing AGE, but implicates dietary AGE may be less important than other aspects of diet that lead to elevated blood sugar levels and formation of AGEs. [4] [5]”

Wikipedia contributors tend to cite irrelevant references rather than get flagged with “citation needed.” The value judgment of sentence 3 was an example of this intentionally misleading masquerade.

“Dietary AGE may be less important..” wasn’t unequivocally supported by studies referenced in either review, and didn’t represent an authoritative body of evidence. Contrast those weasel words with:

“The deleterious effects of food-derived AGEs in subjects with type 2 diabetes mellitus are proven.”

Good job, Wikipedia contributors! You used lower-quality reviews to promote misunderstandings that DETRACTED from science.


Wikipedia’s premise is that since the group knows more about any subject than does any individual, everyone is entitled to contribute. The results are usually incoherent narratives that often substitute opinions for evidence.

The second paragraph of the Exogenous section of the Wikipedia glycation post provided an example:

  • Assertions of the first and third sentences needed citations. Did the contributor(s) think these would be unexamined?
  • Someone contributed a cancer reference as the fourth sentence, although it had little to do with the preceding sentences.
  • The fifth sentence was informative on exogenous glycations and AGEs. An editor would have removed “recently” and “recent” though, because the cited source was dated 2005.
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Disease and advanced glycation end products (AGEs)

This 2015 French/US review focused on chronic kidney disease, appropriate for its publication in the Journal of the American Society of Nephrology:

“Advanced glycation end products (AGEs) are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. Humans are exposed to exogenous sources of AGE (diet and cigarette smoke) and endogenous sources of AGE when the organism is exposed to high levels of glucose, such as in diabetes.

Accumulation of AGEs in patients with CKD has been shown to result from inflammation, oxidative stress, and diet. AGEs are proinflammatory and pro-oxidative compounds that play a role in the high prevalence of endothelial dysfunction and subsequent cardiovascular disease in patients with CKD.

In view of the many harmful effects of AGEs on cell function, it is essential to develop strategies designed to counteract their effects. AGEs are generated during the thermal processing and storage of foods. Dietary restriction is an effective, feasible, and economic method to reduce the levels of toxic AGEs and possibly, the associated cardiovascular mortality.”


I came across the AGE subject in the usual Internet way. 🙂 While reading the comments on Josh Mitteldorf’s blog post Money in Aging Research, Part I, Dr. Alan Green mentioned Dr. Helen Vlassara’s work on the subject. A DuckDuckGo search led to her 31,708 citations the first day I checked. That number increases every day.

Another read on the subject is her 2016 book Dr. Vlassara’s AGE-Less Diet: How a Chemical in the Foods We Eat Promotes Disease, Obesity, and Aging and the Steps We Can Take to Stop It. A practical guide is her 2017 book The AGE Food Guide: A Quick Reference to Foods and the AGEs They Contain.

https://www.researchgate.net/publication/281281887_Uremic_Toxicity_of_Advanced_Glycation_End_Products_in_CKD “Uremic Toxicity of Advanced Glycation End Products in CKD” (registration required)

A better method of measuring neurogenesis

One of the references cited in Linking adult neurogenesis to Alzheimer’s disease was https://www.nature.com/articles/s41591-019-0375-9 “Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease” (not freely available).

This 2019 Spanish human study used improved techniques to find:

“Adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry. Direct evidence of AHN in humans has remained elusive. Determining whether new neurons are continuously incorporated into the human dentate gyrus (DG) during physiological and pathological aging is a crucial question with outstanding therapeutic potential.

By combining human brain samples obtained under tightly controlled conditions and state-of-the-art tissue processing methods, we identified thousands of immature neurons in the DG of neurologically healthy human subjects up to the ninth decade of life. These neurons exhibited variable degrees of maturation along differentiation stages of AHN. In sharp contrast, the number and maturation of these neurons progressively declined as AD advanced.

These results demonstrate the persistence of AHN during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in AD that might be amenable to novel therapeutic strategies.”


The control group was 13 neurologically healthy deceased people aged 43 to 87. The AD group was 45 deceased people, distributed among the six Braak stages of the pathology, aged 52 to 97.

Linking adult neurogenesis to Alzheimer’s disease

This 2019 Spanish human study compared DNA methylation, chromatin and histone modifications in the hippocampus of deceased Alzheimer’s disease patients with controls:

“A significant percentage of the differentially methylated genes were related to neural development and neurogenesis. It was astounding that other biological, cellular, and molecular processes generally associated with neurodegeneration such as apoptosis, autophagy, inflammation, oxidative stress, and mitochondrial or lysosomal dysfunction were not overrepresented.

The results of the present study point to neurogenesis-related genes as targets of epigenetic changes in the hippocampus affected by AD. These methylation changes might be built throughout life due to external and internal cues and would represent an example of epigenetic interaction between environmental and genetic factors in developing AD.

As an alternative explanation, these epigenetic marks might also represent the trace of DNA methylation alterations induced during early developmental stages of the hippocampus, which would remain as a fingerprint in the larger proportion of hippocampal neurons that are not exchanged. This second hypothesis would link AD to early life stages, in concordance with recent studies that revealed abnormal p-tau deposits (pre-tangles) in brains of young individuals under 30, suggesting AD pathology would start earlier in life than it was previously thought. The influence of the genetic risk for AD has also been postulated to begin in early life, and other AD risk factors may be influenced by in utero environment.”


The study cited references to adult neurogenesis:

“Though strongly related to brain development, neurogenesis is also maintained in the adult human brain, mainly in two distinct areas, i.e., the subventricular zone and the subgranular zone of the dentate gyrus in the hippocampus. There is substantial neurogenesis throughout life in the human hippocampus as it is estimated that up to one third of human hippocampal neurons are subject to constant turnover.

Adult neurogenesis is linked to hippocampal-dependent learning and memory tasks and is reduced during aging. Recent evidence suggests that adult neurogenesis is altered in the neurodegenerative process of AD, but it is still controversial with some authors reporting increased neurogenesis, whereas others show reduced neurogenesis. In the human hippocampus, a sharp drop in adult neurogenesis has been observed in subjects with AD.”

One of the study’s limitations was its control group:

“There was a significant difference in age between controls [12, ages 50.7 ± 21.5] and AD patients [26, ages 81.2 ± 12.1], being the latter group older than the former group. Although we adjusted for age in the statistical differential methylation analysis, the accuracy of this correction may be limited as there is little overlap in the age ranges of both groups.”

https://clinicalepigeneticsjournal.biomedcentral.com/track/pdf/10.1186/s13148-019-0672-7 “DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis”

OCD and neural plasticity

This 2019 New York rodent study investigated multiple avenues to uncover mechanisms of obsessive-compulsive disorder:

“Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum) may be causally linked. Numerous genetic and environmental factors may reduce striatum sensitivity and lead to maladaptive overcompensation, potentially accounting for a significant proportion of cases of pathological OCD-like behaviors.

Our results indicate that both the development and reversal of OCD-like behaviors involve neuroplasticity resulting in circuitry changes in BLA-DLS and possibly elsewhere.”


The researchers explored two genetic models of OCD, showed why these insufficiently explained observed phenomena, then followed up with epigenetic investigations. They demonstrated how and the degree to which histone modifications and DNA methylation regulated both the development and reversal of OCD symptoms.

The researchers also carelessly cited thirteen papers outside the specific areas of the study to support one statement in the lead paragraph:

“Novel studies propose that modulations in gene expression influenced by environmental factors, are connected to mental health disorders.”

Only one of the thirteen citations was more recent than 2011, and none of them were high-quality studies.

https://www.nature.com/articles/s41598-019-45325-6.pdf “Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism”

Transgenerational diseases caused by great-grandmother DDT exposure

This 2019 rodent study from the labs of Dr. Michael Skinner at Washington State University found:

“The exposure of a gestating female during fetal gonadal sex determination to DDT can promote the epigenetic transgenerational inheritance of obesity and disease.

Transgenerational pathologies (F3 generation) of late puberty, obesity, testis, prostate, and multiple disease were observed in the DDT lineage males. Obesity, ovarian, kidney, and multiple disease transgenerational pathologies (F3 generation) were observed in the DDT lineage females.

Epigenetic biomarkers or diagnostics provide preliminary evidence for preconception diagnosis of increased susceptibility to transgenerational disease in offspring.”


For those of us who thought DDT was discontinued:

“DDT was banned in the USA in 1973, but it is still recommended by the World Health Organization for indoor residual spray. India is by far the largest consumer of DDT worldwide.

India has experienced a 5-fold increase of type II diabetes over the last three decades with a predisposition to obesity already present at birth in much of the population. Although a large number of factors may contribute to this increased incidence of obesity, the potential contribution of ancestral toxicant exposures in the induction of obesity susceptibility requires further investigation.”

Where are the human studies of this subject? Why aren’t follow-on generations’ diseases traced to the likely sources?

How many F3 great-grandchildren of women exposed to DDT during pregnancy are alive today? Millions, tens of millions?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536675 “Sperm epimutation biomarkers of obesity and pathologies following DDT induced epigenetic transgenerational inheritance of disease”

Infant DNA methylation and caregiving

This 2019 US human study attempted to replicate findings of animal studies that associated caregiver behavior with infant DNA methylation of the glucocorticoid receptor gene:

“Greater levels of maternal responsiveness and appropriate touch were related to less DNA methylation of specific regions in NR3c1 exon 1F, but only for females. There was no association with maternal responsiveness and appropriate touch or DNA methylation of NR3c1 exon 1F on prestress cortisol or cortisol reactivity. Our results are discussed in relation to programming models that implicate maternal care as an important factor in programing infant stress reactivity.”


The study had many undisclosed and a few disclosed limitations, one of which was:

“Our free-play session, while consistent with the length of free-play sessions in other studies, was short (5 min). It is unclear whether a longer length of time would have yielded significant different maternal responsiveness and appropriate touch data.”

The final sentence showed the study’s purpose was other than discovering factual evidence:

“Following replication of this work, it could ultimately be used in conjunction with early intervention, or home-visiting programs, to measure the strength of the intervention effect at the epigenetic level.”

https://onlinelibrary.wiley.com/doi/full/10.1002/imhj.21789 “DNA methylation of NR3c1 in infancy: Associations between maternal caregiving and infant sex” (not freely available)