Healthy Aging: Supporting Healthy Blood Sugar

Supporting Healthy Blood Sugar to Preserve Overall Health

By Chris D. Meletis, ND

This is the fourth part in a series of articles addressing the most common health concerns as we age. Previous parts have discussed cardiovascular disease and weight loss. In this installment I will discuss blood sugar, the destructive effect impaired blood sugar has on many aspects of health and natural support for blood sugar maintenance.

We are constantly consuming foods that can lead us on a direct path to type 2 diabetes. Sugar is omnipresent not only in desserts but also within commonly eaten foods including breads, barbecue sauce, chocolate milk, fruit juices, salad dressings, mustard and ketchup and tomato sauce. Furthermore, these same blood-sugar-disrupting foods are often loaded with destructive compounds known as Advanced Glycation End Products (AGEs).

Blood Sugar, AGES and RAGES

AGEs are formed by the attachment of sugars onto biological proteins or lipids, a process known as glycation. When a sugar links with a protein molecule a harmful process called cross-linking occurs in the body, which causes proteins and lipids to become less elastic and less degradable by enzymes. Cross-linking begins with the Maillard reaction. Anyone who has toasted a slice of bread is familiar with this reaction. When the protein and the carbohydrates in the bread are exposed to heat they turn brown as a result of the chemical reaction that occurred between the proteins and carbohydrates during cooking. The same process occurs in the body, and the final result of this reaction is AGEs.

AGEs accumulate over time, and AGE formation and accumulation is greatly accelerated with high levels of circulating sugars and oxidative stress.¹ AGEs signal through two receptors, one of which is anti-inflammatory (AGER1) and the other is proinflammatory (RAGE). Expression of AGER1 protects against oxidative stress and acute vascular injury. However, over expression of RAGE causes a number of destructive effects.²

Hyperglycemia (high blood sugar) produces reactive oxygen species, which in turn increase RAGE expression.³ This link between AGES and blood sugar is further evidenced by the fact that glycosylated hemoglobin (HbA1c), an example of an AGE, is used as a measurement of blood sugar control in diabetics. Indeed, the fact that red blood cells have a lifespan of approximately 120 days allows for a quantified measurement of glycation damage over a well defined period of time, which can be extrapolated for prognostic long term consequences of uncontrolled blood sugars.

There are important reasons why everyone should be concerned with both AGE accumulation and blood sugar support. High blood sugar, insulin resistance and the excessive number of AGEs that form during hyperglycemia are all linked to numerous health concerns.

Cardiovascular Health

Scientists have found that persistent hyperglycemia is an independent predictor of outcome in acute myocardial infarctions (heart attacks). In a prospective study of heart attack patients, frequent blood glucose measurements were obtained to investigate the relationship between glucose and the occurrence of major adverse cardiac events at 30 days’ follow-up. When the researchers analyzed the data, persistent hyperglycemia emerged as a significant independent predictor of heart attacks.⁴

A similar study in animals demonstrated how high blood sugar can increase AGEs, thereby destroying the health of blood vessels and triggering a decline in cardiovascular health. The study simulated the effects of frequent and excessive sugar intake for a prolonged period on the blood glucose level. The rodents were divided into four groups: 1) a group raised with glucose-enriched feed, 2) a group with ordinary feed, 3) a group with the glucose-enriched feed and special drinking water supplemented with the antidiabetic compound aminoguanidine, and 4) a group with ordinary feed and the aminoguanidine drinking water. After 6 months, the animals’ microvasculature (small blood vessels) was examined. The results indicated that the animals fed the glucose-enriched diet had significantly higher AGEs, smaller arterial microvessels and larger vascular lesion indices, leading the researchers to conclude that microvascular aging was clearly noticed in the group of animals with high glucose.⁵

Both AGEs derived from the diet and AGEs produced in the body can have disastrous effects on heart health. An in vitro study using blood platelets from human volunteers showed that AGEs strongly activate platelets and the activation of platelets is associated with the development of cardiovascular diseases.⁶ The results of this study led the researchers to conclude that concentrations of AGEs that occur in vivo after a meal or a drink can activate platelets’ stickiness and this “points to signaling mechanisms for food AGEs that could favor the precipitation of acute postprandial [post-meal] ischemic events.”

AGEs are linked to negative effects in everyone, but AGEs tend to be most destructive in people with impaired glucose metabolism or type 2 diabetes. One study showed that in individuals who fell into these two categories, the receptor for AGEs (RAGE) was associated with increased blood pressure and arterial stiffness whereas in subjects with normal glucose metabolism these negative effects associated with RAGE were not found.⁷

High blood sugar is also a significant component of the metabolic syndrome, a cluster of abnormalities that also includes hypertension and obesity.

Depression and Cognitive Decline

Diabetes is accompanied by hormonal and neurochemical changes that can be associated with anxiety and depression. High blood sugar and insulin resistance have been linked to depression in numerous studies. In a new study of 1,732 young adults aged between 26 and 36 years, researchers found a positive association between depressive disorder and insulin resistance and the association appeared to be mediated partially by waist circumference.⁸

In another study, depression was associated with duration of diabetes and control of diabetes as measured by fasting blood glucose levels and glucose levels after meals.⁹

Diabetes also is linked to cognitive decline. Blood sugar imbalances impair neurogenesis, the development of new brain cells, and this decline in neurogenesis is linked to the increased number of AGEs that form in diabetics. The antidiabetic compound aminoguanidine has been shown to reduce AGEs while at the same time slowing the impaired neurogenesis that occurs with excessive AGE formation, further establishing the link between brain health and blood sugar.¹⁰

Receptors for AGEs also have been linked to increased accumulation in amyloid-beta peptide (Abeta), the protein linked to Alzheimer’s disease.¹¹

GI Health and Rheumatoid Arthritis

Higher levels of the AGE known as pentosidine are associated with both complications of diabetes and worsening of rheumatoid arthritis. Furthermore, researchers have found that pentosidine expression was up-regulated in the inflamed tissue of inflammatory bowel disease.¹² The urinary pentosidine level correlated with the activity of ulcerative colitis, leading the researchers to suggest that this AGE “may be a marker for disease activity in ulcerative colitis.”

Blood Sugar’s Link to Mutagenic Concerns

Insulin and glucose stimulate cell proliferation and inhibit apoptosis (the programmed cell death by which the body kills abnormal cells) and may therefore influence cancer mortality. Researchers evaluating data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994) found that for every 50 mg/dl increase in plasma glucose, there was a 22 percent increased risk of overall cancer mortality. Insulin resistance was associated with a 41 percent increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin-resistant individuals, specifically among those with lower levels of physical activity.¹³

According to the study authors, “In conclusion, hyperglycemia and insulin resistance may be ‘high-risk’ conditions for cancer mortality. Managing these conditions may be effective cancer control tools.”

In another study, scientists found a particularly strong link between markers of insulin resistance and death from colorectal cancer.¹⁴

Danger in the Diet

Virtually every food that raises blood sugar also either contains AGEs or triggers an increased production of AGEs in the body by inducing hyperglycemia. Additionally, AGEs are produced when food undergoes high heat/prolonged cooking. Deep-fried foods, such as French fries, fried fish and shrimp, fried chicken, etc. are high in AGEs as are well-done meats (including typical fast-food burgers), overly-crisp bacon and burnt toast. A diet high in pre-formed AGEs can seriously elevate blood levels of various inflammatory mediators, including C-reactive protein, tumor necrosis factor-alpha, and vascular cell adhesion molecule.^15-16 A low-AGE diet can lower these inflammatory bio-chemicals.^15-16

According to one group of researchers, “The data support a role for AGEs in the development of renal lesions in aging mice and reveal that AGEs in the diet are very important contributors to renal and cardiovascular lesions.”²

Animal studies also have shown that the reduction of AGE levels by drugs or by decreased intake of AGEs in the diet reduces chronic kidney disease and cardiovascular disease, indicating controlling AGEs can have a significant impact on health.²

Natural Blood Sugar and AGE Control

Because hyperglycemia and the production of AGEs are intertwined I often have my patients who are interested in blood sugar maintenance engage in a regimen that supports both healthy blood sugar levels and reduced levels of AGEs.

Blood sugar support can be achieved by taking a combination of bitter melon, N-acetyl cysteine, goat’s rue, cinnamon, vanadium, quercetin, vitamin C, vitamin E and B6 (all found in GluControl™). Components of bitter melon (Momordica charantia) extract appear to have structural similarities to animal insulin.¹⁷ Bitter melon has reduced blood glucose and lipids in both normal and diabetic animals, protected beta cells, enhanced insulin sensitivity and reduced oxidative stress.^18-19 Vitamins C and E as well as N-acetyl cysteine are especially important to reduce oxidative stress in patients with blood sugar concerns and impaired glucose tolerance.²⁰ This is important because there is a strong link between free radicals and insulin resistance.²¹ N-acetyl-cysteine also improved insulin sensitivity in women with polycystic ovary syndrome.²²

Goat’s rue (Galega officinalis) is important for long-lasting blood sugar maintenance and it causes an increase in carbohydrate tolerance. In one study, goat’s rue extract lowered the blood sugar of diabetic rats by 32 percent.²³ Goat’s rue extract also has supported healthy blood sugar levels in humans.²⁴

Cinnamon is another botanical important for blood sugar control. In humans, cinnamon has improved insulin sensitivity. The improvements were lost after the subjects stopped taking the cinnamon supplements.²⁵

Vandium (vanadyl sulfate) is an important blood-sugar supporting mineral²⁶ while quercetin has been shown to maintain healthy levels of insulin in obese rats.²⁷

For control of AGEs, I have my patients use a mixture of L-carnosine, N-acetyl cysteine, benfotiamine (a fat-soluble form of vitamin B1), guava (Psidium guajava L.), yerba maté (llex paraguariensis) and (R)-lipoic acid (all found in AGEBlock®). Carnosine exhibits antioxidant properties as well as the ability to prevent the formation of AGEs.^28-29 Carnosine inhibits protein modification induced by methylgloxal, a metabolite implicated in AGE formation.³⁰ Methylglyoxal (MG) (pyruvaldehyde) is an endogenous metabolite present in increased concentrations in diabetics and implicated in formation of AGEs and secondary diabetic complications.

The antioxidants N-acetyl cysteine and lipoic acid have been shown to decrease cell death induced by AGEs.³¹ In addition, numerous studies indicate that lipoic acid reduces oxidative stress and prevents the formation AGEs.^32-33 One study found that the combination of benfotiamine plus lipoic acid completely normalized increased AGE formation in type 1 diabetic subjects.³⁴

The botanicals guava and yerba maté also inhibit glycation. Studies have shown that guava extract significantly inhibits low density lipoprotein (LDL) glycation in a dose-dependent manner.³⁵ Yerba maté has been shown to exert significant dose-dependent inhibition of AGE formation.³⁶

Conclusion

High blood sugar and the excessive number of AGEs produced when the body is in a hyperglycemic state are linked to a number of health conditions including cardiovascular disease, depression, cognitive decline, inflammatory bowel disease, rheumatoid arthritis and various forms of cancer. A variety of botanicals, vitamins and nutrients can help maintain healthy blood sugar levels and reduce the number of AGEs produced in the body, preserving optimal health.

References

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