Q&A: How to Reduce Accelerated Glycation End-Products and Increase Healthspan

Excessive sugar consumption can have damaging effects on cognition, according to Christopher Bump, DC, MS, IFMCP, CNS, DABCN, who presented a session on accelerated glycation end-products (AGES) and neurodegenerative disorders at the recent Integrative Practitioner Digital Summit on aging and longevity. 

In the presentation, Bump, a functional medicine chiropractor and clinical nutritionist in Vernon, N.J., said high-sugar intake leads to the accumulation of AGES, which is a fundamental cause of neurodegenerative diseases associated with metabolic syndromes.

According to Bump, reducing AGES in patients can lower their risk for several diseases, prolonging their health span. To reduce or reverse AGES, Bump said, is a multilayered process involving dietary and lifestyle interventions, such as the ketogenic diet, exercise, increased dietary fiber to balance the gut microbiome, and supplements like magnesium, berberine, and black cumin.

We rounded up some of the questions submitted by audience members during the session, which Dr. Bump was kind enough to answer exclusively for our audience. Click here to learn more and register for the next edition of the Digital Summit. 

Q: Could you expand on the connection between sugar and peripheral neuropathy?

Bump: Excess glucose in the blood causes an increase in glycation end-products, which, as you learned, causes an increase in the stimulation of the receptor for AGEs (RAGE). This receptor is on all cell types, but in the peripheral, in the small capillary beds, the endothelial lining is very susceptible to the AGEs. 

Once the RAGE is triggered, an entire cascade of intracellular events takes place, including increased reactive species of oxygen, nitrogen, and sometimes sulphur, along with an associated increase in oxidative and nitrosative stress. This response damages the respiratory chain in the mitochondria, the cellular membranes, and the transmembrane signaling proteins. This leads to cellular damage, then vascular damage, which in turn affects the nerves due to inadequate nutrient supply. 

For more information on peripheral neuropathy and its relation to diabetes I suggest reading the National Institutes of Health Stat Pearls description.

Q: Does Stevia increase AGES?

Bump: Because Stevia is a diterpenoid glycoside derivative, it has no caloric value because there is no sugar of any kind. Therefore, it will not create AGES.

Q: What about allulose?

Bump: A very recent paper called, Allulose in human diet: the knowns and unknowns explores the current state of science on the potential health effects of allulose. I am not excited about allulose as it is a modified sugar our body doesn't recognize well. 

Q: Do other non-nutritive, non-plant-based sweeteners such as Saccharin impact the gut microbiome?

Bump: This is a wonderful question regarding non-nutritive sweeteners (NNS) and the gut microbiome. I recommend reading two current studies exploring the relation, which is inconclusive so far, but of course warrants a continued deeper dive.

The first study reviewed the history and current knowledge of NNS, as well as their impact on host physiology and the gut microbiome. 

The second study summarized results from pre-clinical and clinical investigations over the past ten years that focused on the single effects of the most commonly consumed NNS, including saccharin. 

Q: How long do you recommend patients to stay on the ketogenic diet?

Bump: Depending on how difficult or easy it is for a patient to adhere to a ketogenic diet is how long I recommend for them to stay in ketosis. My experience, which has become the routine Rx, is to get them into ketosis for four weeks or so, then back out and to then rotate back into ketosis on a regular basis. It depends on the patient's compliance, as most find going into ketosis a challenge. I often jump-start them with a five-day water fast to push them quickly into ketosis.

Q: Can you speak about hypoglycemia in patients? These are the folks that don't do well fasting, and blood sugar can be below 85. 

Bump: Hypoglycemia is not a disease state but merely a mismanagement of blood glucose. Individuals who are stressed out, eat on the run, consume lots of sugars and carbs or start their day with coffee and no proteins will push themselves into hypoglycemia.

I recommend to any individual in these categories to first avoid intermittent fasting until they are stable in their glucose regulation, and second, to begin their day with proteins, then a mid-morning snack with protein, and to repeat at lunch. Recall protein stimulates the hormone glucagon, which opposes insulin and facilitates fat for fuel. 

Q: What do you recommend for the duration of treatment for supplements to see changes and then also maintain those changes?

Bump: Three to six months for changes, assuming other lifestyle modifications are made as well. Monitoring for maintenance as needed. Depending on how compromised the patient is will determine how long.

Q: Is berberine safe to take long-term because of its antimicrobial effect? 

Bump: I cannot find any contraindication for using berberine long-term. However, I recommend pulsing any herbal every three months or so by taking patients off for three to four weeks.

Editor’s note: This Q&A was edited and condensed.