EB. 138: How Low-Carb Diets Worsen AGE Formation (and What to Do Instead)

Nov 5, 2025

The discussion highlights how glucose and insulin actually help reduce glycation, contradicting common beliefs about low-carb diets. It reveals that ketogenic diets may elevate harmful substances, leading to increased AGE formation. The role of autophagy in clearing AGEs is explored, but it's emphasized that merely boosting it isn't enough. Practical advice includes optimizing metabolism, managing oxidative stress, and using specific nutrients to support detoxification. The episode redefines the relationship between dietary carbohydrates and glycation risks.

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INSIGHT

Glyoxalase Needs Glutathione To Prevent Dicarbonyls

The glyoxalase system detoxifies methylglyoxal and depends on glutathione availability.
Oxidative stress depletes glutathione and impairs glyoxalase activity, increasing dicarbonyl accumulation.

INSIGHT

Glucose And Insulin Support Glycation Detox

Carbohydrates and insulin support glyoxalase by increasing glutathione and enzyme expression.
Glucose fuels the pentose phosphate pathway to regenerate NADPH and reduced glutathione.

INSIGHT

AGES Already Activate Cleanup Pathways

AGEs themselves trigger autophagy and UPS activation via ROS signaling.
Chronic AGE accumulation often reflects overwhelmed clearance, not lack of autophagy signaling.

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In this episode we discuss:

How glucose and insulin decrease glycation
Why ketogenic diets can be worse than high-carb diets when it comes to AGE formation
How autophagy helps to clear AGEs, but increasing autophagy is not the answer
The true primary drivers of AGE accumulation
The best diet and supplements for minimizing glycation

Check out the Energy Balance Solution program here: https://www.jayfeldmanwellness.com/solution/

Click here to check out the show notes:
https://www.jayfeldmanwellness.com/eb-138-low-carb-diets-increase-glycation-and-what-to-do-instead/

Timestamps:

0:00 – intro

0:57 – how glycation products are detoxified and cleared from the body

4:03 – glycation detoxification is impaired by oxidative stress and inflammation, as seen in type 2 diabetes

7:56 – the benefits of carbohydrates for the detoxification of glycation products

10:42 – the benefits of insulin for the detoxification of glycation products

12:45 – how AGEs are cleared

14:36 – increasing autophagy via hormesis is not the answer for clearing AGEs

19:09 – autophagy can drive disease

20:50 – ATP protects against oxidative stress and allows for proper autophagy when needed

24:37 – impaired mitochondrial along with fatty acid oxidation impairs autophagy and increases oxidative stress

26:54 – carbohydrates do NOT inhibit autophagy

29:18 – adequate thyroid hormone supports proper autophagy

30:15 – adequate ATP and mitochondrial function is needed for the UPS (ubiquitin proteasome system)

32:56 – do high-carb diets actually impair metabolism and insulin sensitivity

35:26 – is fructose really worse for blood sugar regulation and glycation?

37:16 – are low-carb or ketogenic diets the solution to reduce glycation?

40:32 – increased glycation and oxidative stress on ketogenic diets

44:09 –low-carb diets don’t prevent glucose exposure

47:56 – there are still considerable insulin and glucose excursions on low-carb diets

50:06 – gluconeogenesis leads to same glycolytic intermediates as glucose metabolism

51:52 –the main driver of AGE formation and impaired AGE clearance

53:40 – the role of vitamin B1 (thiamine) and mitochondrial energy production in decreasing AGEs

56:27 –endotoxin as a driver of glycation and increased AGE production

58:12 – hypothyroidism as a driver of glycation and AGE accumulation

59:37 – dietary solutions for reducing glycation and AGEs

1:03:33 – how to support the glyoxalase pathway to support the detoxification of glycation products

1:05:56 – avoid calorie restriction, low-carb diets, fasting, resveratrol, cold exposure, excess exercise, and iron overload to decrease glycation and AGEs

1:07:33 – iron as a double-edged sword for oxidative stress