Blood glucose levels in birds are high yet HbA1c levels are low: Can vitamin C have anything to do with this?

Blood glucose levels in birds are often 2-4 times higher than those in mammals of comparable size. Yet birds often live 3 times longer than mammals of comparable size. This is paradoxical. High glucose levels are generally associated with accelerated senescence, but birds seem to age much slower than mammals. Several explanations have been proposed for this, one of which is related to the formation of advanced glycation endproducts (AGEs).

Glycation is a process whereby sugar molecules “stick” to protein or fat molecules, impairing their function. Glycation leads to the formation of AGEs, which seem to be associated with a host of diseases, including diabetes, and to be implicated in accelerated aging (or “ageing”, with British spelling).

The graphs below, from Beuchat & Chong (1998), show the glucose levels (at rest and prior to feeding) and HbA1c levels (percentage of glycated hemoglobin) in birds and mammals. HbA1c is a measure of the degree of glycation of hemoglobin, a protein found in red blood cells. As such HbA1c (given in percentages) is a good indicator of the rate of AGE formation within an animal’s body.

The glucose levels are measured in mmol/l; they should be multiplied by 18 to obtain the respective measures in mg/dl. For example, the 18 mmol/l glucose level for the Anna’s (a hummingbird species) is equivalent to 324 mg/dl. Even at that high level, well above the level of a diabetic human, the Anna’s hummingbird species has an HbA1c of less than 5, which is lower than that for most insulin sensitive humans.

How can that be?

There are a few possible reasons. Birds seem to have evolved better mechanisms to control cell permeability to glucose, allowing glucose to enter cells very selectively. Birds also seem to have a higher turnover of cells where glycation and thus AGE formation results. The lifespan of red blood cells in birds, for example, is only 50 to 70 percent that of mammals.

But one of the most interesting mechanisms is vitamin C synthesis. Not only is vitamin C a powerful antioxidant, but it also has the ability to reversibly bind to proteins at the sites where glycation would occur. That is, vitamin C has the potential to significantly reduce glycation. The vast majority of birds and mammals can synthesize vitamin C. Humans are an exception. They have to get it from their diet.

This may be one of the many reasons why isolated human groups with traditional diets high in fruits and starchy tubers, which lead to temporary blood glucose elevations, tend to have good health. Fruits and starchy tubers in general are good sources of vitamin C.

Grains and seeds are not.

References

Beuchat, C.A., & Chong, C.R. (1998). Hyperglycemia in hummingbirds and its consequences for hemoglobin glycation. Comparative Biochemistry and Physiology Part A, 120(3), 409–416.

Holmes D.J., Flückiger, R., & Austad, S.N. (2001). Comparative biology of aging in birds: An update. Experimental Gerontology, 36(4), 869-883.