From dementia to mental health and behavior effects, and what to do about it
By Austin Perlmutter, MD
To think, act and feel in any way, your brain requires access to large amounts of consistent energy. For most of us, that energy comes in the form of blood sugar (glucose) which is transported into the brain and used by our brain cells. While it’s been well known that very high and very low blood sugar levels can have acute and significant negative effects on brain function, research is now showing us that long-term blood sugar issues may also play a significant role in our mental and especially our cognitive state. In this article, we’re exploring how blood sugar influences brain health and practical strategies that speak to this science.
Despite a weight of only a few pounds, your brain uses up around 20-25% of your body’s blood sugar (double what a chimpanzee uses!) The brain can use other forms of fuel as energy, including ketones and lactate, but for most people this makes up a relatively small percentage of total brain energy. Our blood sugar levels go up and down throughout the day, typically rising after meals and then reaching a lower level after longer periods between meals. Blood sugar levels are often measured in milligrams per deciliter of blood (mg/dL.) Blood sugar levels are typically measured in labs after fasting, and a usual range for this metric is around the 70-100 mg/dL mark. When blood sugar is very high (e.g., over 300 mg/dL) or very low (e.g., less than 55 mg/dL), there is a much higher risk for having acute alterations in mental status and in the case of extremes, even coma.
A rapid development of very high or very low blood sugar levels and the resultant alterations in brain state is far more likely to occur in people with diabetes, although there are other causes. However, we’re now learning that long-term, more subtle changes in blood sugar may also have a significant effect on brain health and brain state. For example, simply having type 2 diabetes (which affects about 1 in 10 Americans) may translate into an over 50% increase in risk for developing Alzheimer’s disease, and a doubling of risk for being diagnosed with a mental health condition.
What about people who haven’t yet developed diabetes? In a telling 2023 publication, prediabetes (which impacts about 40% Americans and 50% after age 65) was found to significantly increase the chances of getting any type of dementia. Having prediabetes may also increase risk for depression, especially in younger people (based on the results of a 2024 meta-analysis). Shockingly, over 80% of people with prediabetes don’t know they have the condition.
How do blood sugar levels influence brain health?
There are many proposed pathways linking blood sugar alterations to brain health issues. At a very basic level, we can think about our brain’s constant need for regular access to glucose as key to our brain health, and anything that compromises that flow can lead to brain health issues. Hypoglycemia (abnormally low blood sugar) leads to an explicit lack of energy to power our neurons, and in animal data is shown to impair neurotransmitter signaling. Other pathways include generation of oxidative stress and damage to mitochondria.
On the opposite end of the spectrum, high blood sugar is linked to brain dysfunction through the direct toxicity of elevated glucose levels, as well as through problems with insulin signaling (this tends to accompany diabetes). Additionally, high blood sugar may lead to brain cell growth suppression and even death in the hippocampus (a part of the brain key to long-term memory) as well as elevated inflammation, vascular damage, impairment in the blood brain barrier, mitochondrial issues, increased oxidative stress, and problems with synapses.
Beyond these direct effects of high and low blood sugar on the brain, recent research suggests that too much variability in blood sugar may also act on many of the same pathways that contribute to brain issues, including inflammation and elevated oxidative stress. This means the brain risks related to blood sugar may not be all about peaks and valleys but rather how often and how quickly blood sugar goes up and down.
How do brain pathways influenced by blood sugar impact cognitive and mental health?
Of the many mechanisms tethering blood sugar issues to brain cells, almost all are believed to directly contribute to brain health issues like rapid brain aging, dementia and depression, as well as even impulsive behavior and violence. The implications here are profound: if alterations in healthy brain energy are being driven by a growing epidemic of blood sugar dysfunction and this activates unhealthy pathways linked to a range of brain diseases, we must see improved blood sugar balance as a top priority as a population.
What steps can be taken?
When it comes to blood sugar issues, it’s important to note the need for different approaches based on an individual’s biology, diagnoses and unique life circumstances. For those with diseases that require prescription medications or medical supervision, there is much more need for caution before making changes. With this said, it’s also key to note that we’ve moved away from an era where blood sugar issues are rare, and increasingly into a time where almost everyone would benefit from taking a closer look at their blood sugar regulation and the risk it poses to brain health.
5 of the best tools available at this time include:
Learn about your own biology. As described, most people with blood sugar issues don’t know they have them. An excellent way to gain insight into this system is to make sure you are getting your regularly indicated labs (including a fasting blood sugar and hemoglobin A1C (HbA1c)). Other labs to consider include a fasting insulin (which can give early insight about risk for diabetes). Beyond this, using a continuous glucose monitor (CGM) can be a helpful way to see how your blood sugar fluctuates with meals and other
Eat a balanced diet rich in fiber, phytochemicals, protein and healthy fat, and low in added sugars and refined carbohydrates. While many diets have been made popular, the best studied diets for brain health are the Mediterranean and its variants (e.g., the MIND diet). The combination of nutrients prioritized in these minimally processed diets have several beneficial effects on brain-related and blood sugar related pathways. These diets are also shown to be protective against blood sugar issues like the development of diabetes.
Prioritize regular exercise that includes weight training. Exercising has a number of well-established benefits on brain health and blood sugar control. While aerobic exercise is important, a number of recent publications have demonstrated that weight training our large muscle groups (think your legs!) can be especially beneficial for blood sugar management because exercising skeletal muscle pulls glucose out of circulation and into muscle.
Work on mitigating chronic stress. Though the pathways are somewhat complex, research indicates that chronic stress damages healthy blood sugar control and impairs healthy brain function. In diabetics, more work stress in particular related to higher blood sugar levels. Though stress can’t be completely removed, interventions like mindfulness, time in nature, breathwork and others can help to decrease the effects. Psychotherapy or other professional help is also a good consideration with those experiencing significant levels of ongoing stress.
Work to get 7-8 hours of sleep a night. Good sleep is about the most important thing we can give our bodies and our brains. Research suggests that those getting too many or two few hours of sleep a night are at higher risk for developing type 2 diabetes. Altered sleep patterns are also linked to risk for dementia. To improve sleep quality, work to create a consistent sleep routine and if still struggling, consider a professional sleep evaluation.