Metabolic Memory: How High Blood Sugar Affects Your Health Even After it's Gone

Did you know that your body “remembers” your blood sugar levels from five years ago?

Human bodies are living histories - if we could read the stories written in our own cells, we’d see our own lives reflected in our stress hormone levels, gut biome composition, and DNA methylation. While you’re getting on with your day, your cells are busy creating and re-creating your physical history from the last 20 (or 40, or 60, or 80) years you’ve spent on this planet!

One practically relevant aspect of this is metabolic memory*. To put it simply, if you ate a lot of junk and had a lot of blood sugar issues before finding Paleo, then the consequences of that diet are likely still following you around. Having high blood sugar causes long-term changes that stick around even after your blood sugar itself is fine.

*(Just to clarify, metabolic memory has nothing to do with the homeopathic concept of “molecular memory,” the idea that water “remembers” other things you mix with it.)

But here’s the good news: you’re in charge of writing the next chapter of your body’s history. It takes time and patience (you’re rewriting huge chunks of your cellular biology; it’s not a one-afternoon project), but if you want to make new physical “memories” of good blood sugar control, you’re the one in charge!

Metabolic memory: how blood sugar problems stick around

Metabolic memory was first discovered in people with type 1 diabetes. If patients had poor blood sugar control early in life, side effects like cardiovascular disease persisted even years after their blood sugar itself was fine. The longer patients had high blood sugar, the worse they did even after bringing their blood sugar down. Further studies found that this was also true for type 2 diabetes.

Very intensive early treatment starting from the very first stages of the disease can significantly reduce this effect, but a lot of people only realize they have a problem after they’ve already had uncontrolled blood sugar for a while.

How metabolic memory works

High blood sugar starts up a cycle of inflammation, oxidative stress, and epigenetic changes - then that cycle becomes self-sustaining.

This review names four ways that high blood sugar causes long-term metabolic changes that act like a physical “memory” of the blood sugar issues:

• High blood sugar causes oxidative stress (basically, inflammatory damage to your cells; antioxidants are good for you because they fight oxidative stress)
• High blood sugar increases production of AGEs (Advanced Glycation End-products)
• High blood sugar changes gene expression (epigenetics) - not your actual genetic code, but which genes are turned on or off.
• High blood sugar causes chronic inflammation, which is involved in every major “side effect” of diabetes, from vision problems to heart disease.

At a certain point, these secondary issues become self-perpetuating, which is how blood sugar spikes still have "echoes" in your biology long after the fact.

Effects of metabolic memory

Those four problems above (oxidative stress, AGE production, epigenetic changes, and inflammation) increase the risk of “high blood sugar symptoms,” even when the high blood sugar itself is gone.

For example, metabolic memory is one reason why even people with good blood sugar control can get diabetic retinopathy (vision loss or blindness caused by diabetes). Controlling blood sugar doesn’t prevent eye damage because it doesn’t reverse oxidative stress and epigenetic changes in the eye tissue.

Poor blood sugar control also changes biochemical pathways and DNA expression in the kidneys. This ultimately reduces uric acid clearance and increases inflammation. These effects stay - and keep damaging kidney health - even if blood sugar is controlled.

Finally, there’s heart disease. In this study of patients with type 2 diabetes, controlling blood sugar didn’t prevent death from heart disease even after 5.6 years. The researchers chalked this up to metabolic memory: even after controlling their blood sugar, the subjects still had heart problems thanks to the inflammation and oxidative stress left over from their previous blood sugar issues.

Rewriting metabolic memory

And now for the less depressing part of the program: studies exploring ways to rewrite the metabolic memories of high blood sugar into something better.

Antioxidants - if the timing is right

The authors of this paper stress that just downing antioxidant supplements isn’t super helpful in people who don’t also have their blood sugar under control. But the researchers did note that antioxidant treatment in conjunction with blood sugar control could be the answer.

That’s backed up by this clinical trial - in 36 people with diabetes, some got only insulin to normalize their blood sugar; others got insulin + vitamin C, an antioxidant. The vitamin C group did much better. Even after both groups had normal blood sugar, the insulin-only subjects still had damage to their blood vessels. The vitamin C group had much less damage, showing that vitamin C helps to reduce the metabolic memory effect.

This suggests that vegetables and fruits rich in vitamin C might be helpful for people recovering from metabolic problems. If you're low-carbing as part of your plan, vitamin C-rich vegetables like bell peppers are probably a better choice than citrus fruit.

Fasting or calorie restriction, maybe

Then there’s the question of calorie restriction.

In mice, even short-term calorie restriction (4 months at 60% of maintenance calories) created “good” metabolic memories - it reduced inflammation and improved glucose tolerance even after the mice went back to eating normally. This study (also in mice) found the same thing.

Is the same effect true for humans? On the one hand, you’re not a mouse. On the other hand, there’s quite a bit of evidence on the epigenetic and metabolic benefits of intermittent fasting, periodic longer fasts, and other forms of food restriction in humans, so it seems plausible.

Time and consistency

Finally, this paper suggested that subjects could make new metabolic memories after enough time with good blood sugar control - it just takes a really, really long time. Specifically, in that paper, subjects with type 1 diabetes took 10 years to heal from diabetic kidney disease after getting transplant pancreas (which allowed them to have normal blood sugar control).

The “so what?”

For people who don’t already have metabolic problems, this is why it’s ideal to prevent them before they happen - once you have blood sugar problems, they’re hard to heal.

For people coming to Paleo after years (or decades) of blood sugar issues, the research on metabolic memory suggests that you should take your own body’s history into account in setting up your plan. Out-of-the-box Paleo is specifically designed to address issues like oxidative stress, inflammation, and AGE formation, but research suggests that optional tweaks like intermittent fasting might be particularly helpful.

And finally, these studies really illustrate the time and patience necessary to make deep changes to your health - it’s a lifelong process, not something that’s over in 30 days or 15 pounds!