Monday, October 11, 2010

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.

22 comments:

Jenny said...

I doubt the vitamin C is the explanation. Many of the other animals listed also synthesize Vitamin C. And every large study of humans to date has found negative outcomes associated with Vitamin C supplementation.

Red blood cell turnover would explain the the low A1c handily. Humans with longer lived red blood cells will see higher A1cs at identical blood sugar levels as people with shorter lived cells and people with anemia see very low A1cs even when they have blood sugars high enough to give them severe diabetic complications--which are not prevented by low A1c.

The very high energy consumption of birds probably explains why they have high blood sugars as a bird who runs out of glucose in mid-flight is going to be a dead bird.

john said...

Ned,

In this (http://onlinelibrary.wiley.com/doi/10.1002/pros.20683/pdf) example, mice on the ketogenic diet had the highest blood glucose levels (which even increased throughout the study) yet the lowest tumor growth. Note the insulin was the lowest though.

Jenny,

I think birds mostly use fat, even during flight. Here is one example: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B73GK-485998J-JH&_user=10&_coverDate=08%2F01%2F1970&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=4d31f0c1a50ab7828d872e7b531f2220&searchtype=a

David Isaak said...

"And every large study of humans to date has found negative outcomes associated with Vitamin C supplementation."

Every large study conducted with Vitamin C has been poorly designed and has generally used tiny amounts of Vitamin C in single doses. Since the half-life of Vitamin C in the body is 30 minutes, a single daily dose, even many many times the RDA, is not going to show the same results that Pauling projected.

I put zero credibility in the large-scale studies of Vitamin C.

Your point about red blood cell turnover, however, is a good one.

Anonymous said...

Sounds too simple and great points from Jenny. But Pauling asked a very good question, why do vitually all animals synthesize all that vitamin C it's difficult to believe there is no benefit .

Vitamin C is the explaination for something animals.

Anya said...

Ned,

Intresting, I think there is more to this then meets the eye. Vitamin C is only 4 small enzyme steps away from glucose. Did you know that supplementing with vitamine C lowers blood sugar levels ?
Also, zero to very low carb diets can lead to scurvy (except when eating your meat raw and including offal) ?

Maybe our human desire for carbs is nothing more then a quest for vitamin C and/or it's building blocks ?


There are theories that atherosclerosis, heart attack, and stroke are nothing more then chronic low grade scurvy caused by chronic high blood sugar.

For more info search for Glucose-Ascorbate Antagonism (GAA) theory by Dr John Ely

Ned Kock said...

Hi Jenny.

Vitamin C has been shown to have a number of positive effects, most disease prevention-related, including some not very obvious ones. For example, it seems to increase the capacity of the endothelium to release tissue plasminogen activator (t-PA) in overweight and obese folks.

Ned Kock said...

Hi john.

Interesting. Mice have higher glucose levels than humans, an lower A1c. They produce vitamin C.

Bats, on the other hand, don't produce vitamin C. Members of the primate suborder (clade) Haplorrhini ("dry-nosed" primates) don't produce vitamin C either. That includes humans.

Hummingbirds display a range of odd and fascinating metabolic swings:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325055/?report=abstract&tool=pmcentrez

Ned Kock said...

Hi David.

Pauling seems to have been a big fan of vitamin C, lysine and niacin as treatments for high Lp(a). Of the three, niacin (in megadoses) is the one with the most success, I believe.

Ned Kock said...

Hi Anon.

There is a theory that Lp(a) was evolved as, oddly enough, a substitute for vitamin C in the animals that don't synthesize it (e.g., the Haplorrhini):

http://www.pnas.org/content/87/16/6204.full.pdf+html

Pauling is the co-developer of this theory. He also argues that when vitamin C levels are elevated, Lp(a) levels go down. I don't think that has been demonstrated in humans though.

Ned Kock said...
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Ned Kock said...
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Ned Kock said...

Hi Anya.

THAT is an interesting theory!

By the way, this randomized trial with humans shows that short-term vitamin C supplementation significantly decreases resistin levels.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865087/?report=abstract&tool=pmcentrez

Elevated resistin levels seem to interfere with the role of insulin in reducing blood sugar levels. So the study supports the effect you mentioned. It is an indirect effect.

Life is not that simple!

Ned Kock said...

Vitamin C production in animals seems to be quite high, so we may have a similar situation to that of vitamin D here (a LOT is produced from sunlight, much more than is available through the SAD).

For instance, an average goat will produce more than 6 g per day. The Gov RDA is 60 mg. That is 100 times less vitamin C than a goat produces. And a goat weighs much less than a human.

There is something wrong with this picture ...

john said...

But, a vitamin C intake that high (proportional to a goat's production) using real foods is near impossible. I think vitamin C supplement trials have pretty mixed results.

David Isaak said...

"I think vitamin C supplement trials have pretty mixed results."

Boy, that's the truth. And also have such mixed approaches that mixed results would be expected.

On the other hand, no decent study has ever shown much of a downside to megadosing Vitamin C (and not for lack of trying), so this is an area where one can feel free to self-experiment.

Erik said...

There's an interesting thread over at Mind and Muscle on Vitamin C. Pretty compelling stuff:

http://www.mindandmuscle.net/forum/index.php?showtopic=12967

Erik said...

Further, animals already produce large amounts of Vitamin C, but they produce even more when sick.

Vit. C bowel tolerance in humans increases with illness, possibly suggesting an increased demand for it in the body.

Ned Kock said...

"But, a vitamin C intake that high (proportional to a goat's production) using real foods is near impossible."

I agree. But given the large disparity, and the fact the vitamin C is essential for human health, it is possible that the ideal daily intake is a lot higher than the Gov RDA.

One can easily get 200 mg from fruits and vegetables. Maybe an intake in the 200-1000 mg range would be natural. It may not fix major health problems, but may help prevent them.

Megadosing may lead to benefits under certain circumstances.

Ned Kock said...

Hi Erik, thanks.

Ned Kock said...

I was looking for a table showing the vitamin C production of various animals, including birds. Couldn't find it on one single source, just bits and pieces here and there.

It seems that those animals that produce the most vitamin C per unit of weight are the ones with the biggest glucose-A1c gap. This lends some support to the hypothesis that vitamin C reduces glycation.

Some numbers are available from this interesting paper by Sardi, who claims that vitamin C can increase longevity in humans:

http://www.lewrockwell.com/orig/sardi9.html

Also, in case you don't know and would like to know, the plant food with one of the highest known concentrations of vitamin C is a fruit called acerola. According to this wiki, it has 1.6 g of vitamin C per 100 g of fruit:

http://en.wikipedia.org/wiki/Acerola

Ned Kock said...

Just came across this study, almost by chance:

http://care.diabetesjournals.org/content/23/6/726.short

Of relevance:

"CONCLUSIONS: An inverse association was found between plasma vitamin C and HbA1c. Dietary measures to increase plasma vitamin C may be an important public health strategy for reducing the prevalence of diabetes."

Ned Kock said...

As it turns out, there seems to be another fruit that beats acerola in terms of vitamin C content. It is the Kakadu plum:

http://en.wikipedia.org/wiki/Kakadu_plum

Apparently it has been part of the traditional diet of the Australian Aborigines for thousands of years. Its reported vitamin C content is a whopping 3-5 g per 100 g of fruit!