Your diet is by far the biggest contributor to AGEs. Under normal circumstances, your body has mechanisms to eliminate these harmful AGE compounds, such as specific antioxidants and enzymatic pathways. (3, 4) However, these pathways can be overwhelmed when you consume too many foods containing or promoting the production of AGEs. They can accumulate in your body in large numbers over time and cause devastating, and even toxic effects via oxidative stress (5) and inflammation. (6) Hence the name glycotoxic for this subtype; the brain is literally poisoned by excessive amounts of sugar.
GLYCOTOXIC
SUBTYPE OF ALZHEIMER’S DISEASE
I teach my patients that there are two things that are absolutely critical to understand about Alzheimer’s disease:
1. Your DNA does not determine your destiny—your gene expression can be turned on and off.
2. There is a mountain of research showing that your risk of Alzheimer’s disease and dementia can be drastically reduced by your lifestyle choices.
If you understand those two key points, then you know that Alzheimer’s is not a disease that you need to be afraid of. Maybe you know you have genetic risk or watched a loved one suffer from this personality and memory-robbing disease. Or maybe you are having symptoms of cognitive decline right now… not focusing or thinking as well as you used to, or experiencing memory issues or brain fog.
Cognitive decline is not just another sign of aging. It’s a sign that something is wrong. But more importantly, it’s a sign that there is something that we can work to fix.
While these lifestyle questions show that you may be more at risk for the glycotoxic subtype of Alzheimer’s, we recommend that you look deeper into what your unique set of risks is.
When you can pinpoint your areas of weakness, it gives you a blueprint for preserving your future…. memories, personality, and all!
Your future is worth it.
8 SIGNS OF GLYCOTOXIC
Poor Short
Term Memory
Difficulty learning new things and storing new memories and information.
Better Long
Term Memory
No problems recalling memories from when you were younger.
Brain
Volume Loss
Measurable loss in the hippocampus region of the brain.
ApoE
Genetic Risk
One copy of ApoE4 gives you a 30% chance of getting AD. Two copies give you a 50% chance.
Elevated
Glucose Levels
Elevated fasting and average (hemoglobin) glucose.
Elevated
Insulin
Levels
Elevated insulin levels can be an early warning sign.
Elevated
Triglyceride Levels
Fats from excess calories (especially simple carbs).
Elevated
Inflammatory Markers
AGEs can produce significant inflammation.
The glycotoxic subtype of Alzheimer’s disease (AD) consists of many elements of the inflammatory and atrophic subtypes. However, it is unique in that the damage to the brain is specifically due to elevated levels of blood sugar (glucose) and insulin.
SUGAR:
Insulin Resistance
When glucose levels in the blood remain elevated, and your body increases insulin more and more to try to get the excess sugar out of the blood and inside the cells (neurons and glial cells), you can actually develop insulin resistance in the brain. This is a problem because insulin is an important growth factor for nerve cells. If neurons can’t utilize insulin efficiently, it impairs their ability to grow, as well as to make and retain important connection networks with other neurons. (1) Since insulin resistance is a major contributing factor in the development of diabetes, many people have termed Alzheimer’s disease “Type 3 Diabetes”.
HIGH-TEMP COOKING:
Advanced Glycation End Products (AGEs)
There are harmful compounds that are produced when certain foods are cooked at high temperatures, such as during grilling, frying, or broiling. It creates a caramelization process (think of the beautiful dark brown grill lines on your favorite cut of meat or the flame-broiled caramelized top of that delicious creme brulee). These caramelized compounds have been termed advanced glycation end products or AGEs. AGEs are formed inside our bodies as well when certain proteins or fats combine with excess sugar in the bloodstream. This process of sugar sticking to another compound, cell or tissue in the body is called glycation. (2)
SUGAR TOXICITY:
Brain Poisoning
GLYCOTOXIC ALZHEIMER’S DISEASE
SIGNS & SYMPTOMS
The glycotoxic subtype of AD, like the inflammatory subtype, most often begins with the loss of ability to store new information and new memories, and also a harder time learning new things. Interestingly, long-term memory is not lost, especially in the earlier stages of the disease process. This means that people can recall sometimes minute details of events that happened 30, 40, or even 50 years ago, but may not be able to remember their conversation from five minutes ago. They also, like people suffering from the inflammatory subtype, initially retain their ability to speak, perform mathematical calculations, spell, and write.
The symptoms not only result from atrophy of the memory centers of the brain (especially the hippocampus) but also because support for brain synapses (where one nerve connects to another) has dried up. This means that the ability to pass along signals from one area of the brain to another, or from the brain to different parts of the body, is compromised. This process develops slowly and often the symptoms aren’t recognized by the patient, so he/she will frequently protest that nothing is wrong.
GENETICS FACTORS
Since the glycotoxic subtype is an overlap of the inflammatory and atrophic subtypes, it is also more commonly associated with the higher risk ApoE4 gene, whether homozygous (two copies) or heterozygous (single copy). We each receive two copies of the ApoE gene (one from each parent), and the possibilities are ApoE2, 3, or 4. It is most common for people to inherit two copies of the ApoE3 gene, which carries with it just a 9% risk of developing Alzheimer’s disease. In contrast, having a single copy of the ApoE4, which is seen in about 25% of Americans, increases one’s genetic risk to 30%. Having two copies of ApoE4, seen in a little over 2% of the population, carries a much higher risk.
U.S. population, increases the risk to greater than 50%. People who inherit two copies of the ApoE4 gene typically begin experiencing symptoms at a younger age, with their onset typically in their late forties or fifties. With just one copy of this gene, the onset is about a decade later. With no ApoE4 gene, the onset is more often in their upper sixties or seventies.
LAB INDICATIONS
Different subtypes can’t always easily be distinguished by lab testing, but there are some unique findings in the glycotoxic subtype that are worth mentioning. As you might expect, the most common lab findings in this subtype include an elevated fasting glucose (>90 mg/dL) and average glucose, aka hemoglobin A1C (>5.6%). Elevated insulin levels are frequently seen, and can sometimes arise as an earlier warning sign before significant glucose elevations show up on the labs. Fasting insulin levels >9 uIU/mL or c-peptide (provides some idea of a longer-term, more average insulin) levels ≥2 ng/mL should be addressed.
Elevated triglyceride levels (>90 mg/dL) often go hand in hand with elevated sugar and insulin levels, as triglycerides are fats that are produced when excess calories, and particularly excess simple carbs, are consumed. As we discussed above, the AGEs can produce significant inflammation, so frequently elevated inflammatory markers are seen, including c-reactive protein (CRP) levels >1 mg/L. Target levels for these nutrients and hormones aren’t always the levels shown as normal by different lab companies. Discuss them with a practitioner trained in optimizing and personalizing these lab findings.
There has been a vast increase in sugar intake in the last 100 years. In fact, many populations are eating an average of 4 times more than the recommended amount of sugar! The dramatically rising rates of Alzheimer’s disease are due in large part to this poisoning of our brains.
Dr. Scott Noorda, D.O. IFMCP
Founder Of The Brainlift Program
REFERENCES
Bredesen, D. (2017). The End of Alzheimer’s: The first program to prevent and reverse cognitive decline. Penguin. p. 104.
Schmidt, A. M., Hori, O., Brett, J., Yan, S. D., Wautier, J. L., & Stern, D. (1994). Cellular receptors for advanced glycation end products. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 14(10), 1521-1528.
Wu, X., & Monnier, V. M. (2003). Enzymatic deglycation of proteins. Archives of Biochemistry and Biophysics, 419(1), 16-24.
Conner, J. R., Beisswenger, P. J., & Szwergold, B. S. (2005). Some clues as to the regulation, expression, function, and distribution of fructosamine‐3‐kinase and fructosamine‐3‐kinase‐related protein. Annals of the New York Academy of Sciences, 1043(1), 824-836.
Yamagishi, S. I., Maeda, S., Matsui, T., Ueda, S., Fukami, K., & Okuda, S. (2012). Role of advanced glycation end products (AGEs) and oxidative stress in vascular complications in diabetes. Biochimica et Biophysica Acta (BBA) – General Subjects, 1820(5), 663-671.
Hong, Y., Shen, C., Yin, Q., Sun, M., Ma, Y., & Liu, X. (2016). Effects of RAGE-specific inhibitor FPS-ZM1 on amyloid-β metabolism and AGEs-induced inflammation and oxidative stress in rat hippocampus. Neurochemical Research, 41(5), 1192-1199.