Glucose and the Stomach Flu—Starving a Fever

tl;dr: Sometimes grandmothers get it right.

So I got sick. For the first time in such a long time that I have trouble remembering the last time... That's been one of the biggest benefits of the Paleo diet, as the flu used to visit like clockwork.

This one was a stomach bug—it's apparently going around, from the symptoms I'd say it's viral.

The immediate sign of it was that the mere thought of food was enough to make me nauseous and dizzy. At which point I decided that instead of getting lunch I would leave the office and go home.

Later, in the evening, my daughter broke out some ice cream. That was appealing!

After eating a few bites I came down with a fever. Literally, in the middle of eating the bowl of ice cream I started getting chills. 99.5, not huge, but I hadn't had a fever prior to that moment.

A few hours later the fever went away.

Which got me to thinking: cause and effect?

The old saw is "feed a cold, starve a fever". Starvation, of course, leads to a ketogenic state. We have at least one instance of a guy improving a serious viral disease by going on a ketogenic diet (Henderson, 2014).

One of the ways your body disposes of excess carbs is by increasing the metabolic rate. Which is basically what a fever is. And the fact that your body can anticipate the effect of glucose on the metabolism is, as they say, well-established.

So was my two-hour fever after eating some ice cream my body's way of getting rid of the glucose, which it recognized was counter-productive?

I didn't eat anything else until the following evening, and nothing that was high-carb, and the fever didn't come back. But I also didn't try eating more ice cream (which had lost it's appeal after my body reacted to it; I wanted to get better, not conduct an experiment).

Of course the doctors will tell you (Fischetti, 2014) that you should eat when you have a fever, because your body needs calories. Oy vey... I'm going to stick with grandma's advice: you've got plenty of calories, losing a few pounds (I lost 5) won't kill you, and you should listen to your body. Nausea's about the clearest sign you're going to get...

OK, well that's a nice hypothesis, but it's based on an anecdote. Any support in the scientific literature?

"Specifically, they could suppress viral infection of cells by dismantling the V-ATPase through the lowering of glucose levels. In addition, they could inhibit infection by treating cells with chemical inhibitors of glycolysis, the initial pathway of glucose catabolism. Conversely, influenza viral infection of cells could be increased by giving cells more glucose than normal, the researchers report in the journal Virology [(Kohio, 2013)].

"The ease with which the researchers could dial viral infection down by controlling glucose levels and thus V-ATPase activity suggested a new strategy for throttling influenza viral infection. "Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection," say Adamson and Kohio."

"Turning Down Glucose Metabolism in Cells Slows Influenza Infection, Suggesting a New Strategy for Flu Therapy" (ASCB, 2013)

Figure 1 (Kohio, 2013)

A "new approach". Yeah, listen to grandma, that's radical. Now it's entirely possible that different virii work in different ways, but it does lend some support to the "starve a fever" argument, as starvation (aka ketogenesis) is the easiest way to suppress glucose metabolism!

There's also this, which might explain how virii can lead to cancer:

"Viruses and Metabolism: Alterations of Glucose and Glutamine Metabolism Mediated by Human Cytomegalovirus." (Yu, 2011)

Turns out the little buggers use glucose to make more virii, which is of interest, as they've been trying to figure out the relationship between this virus and cancer for decades:

"The Story of Human Cytomegalovirus and Cancer: Increasing Evidence and Open Questions" (Michaelis, 2009)

BTW, I managed to not follow ALL of the advice the doctor offered in the Scientific American article linked to above:

"Fact or Fiction?: Feed a Cold, Starve a Fever" (Fischetti, 2014)

I drank caffeine, despite this: "Caffeine enhances dehydration." That advice is just not correct (Zeratsky, 2023), unless you're not used to drinking caffeine. I drank a little vodka last night to settle my stomach, despite this: "Avoid caffeine and alcohol." I have no idea why that worked, but it certainly didn't make things worse, and it helped me sleep. Of course an alcoholic hot toddy is another old grandmother's cure. (I'd make mine minus the sugar, of course.)

The flu did not progress to a more serious case. After a few years of checking doctors' recommendations on many topics:

I've learned you're better off ignoring them on a lot of matters. Unless you have a traumatic injury. Especially when they've not read the literature, which is more often than you would expect.

P.S.

Apparently the relationship between glucose metabolism and influenza has been known since the 1950s:

"The relatively low toxicity in both experimental animals and humans of the potent glucose antimetabolite 2-deoxy-D-glucose suggested the feasibility of employing this compound in in vivo influenza virus infection. The present studies, undertaken in the intact chick embryo, demonstrate that the synthesis of influenza virus is markedly inhibited by 2-deoxy-D-glucose. Ancillary studies with in vitro systems show this inhibition to be reversible with glucose and therefore not related to permanent host cell damage." (Kilbourne, 1959)

And in diabetic mice in 1998:

"The extent of viral replication in the lungs was proportional to blood glucose levels in the mice at the time of infection, and the enhanced susceptibility of diabetic mice was reversed with insulin...."

Although (as I cautioned about above) it doesn't seem to work for all strains:

"...Growth of A/HKx31 (H3N2) virus was also enhanced in diabetic mice, whereas the highly virulent strain A/PR/8/34 (H1N1) showed no difference in virus yields in diabetic and nondiabetic mice..." (Reading, 1998)

So it's worth a shot, as it seems the worst thing that's going to happen is nothing. There don't seem to be any studies done on a ketogenic diet and influenza, however. That would be interesting.

Original post: May 14, 2014

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References

The American Society for Cell Biology. (2013, December 21). Turning Down Glucose Metabolism in Cells Slows Influenza Infection, Suggesting a New Strategy for Flu Therapy [Blog]. The American Society for Cell Biology. https://web.archive.org/web/20131221055018/http://www.ascb.org/ascbpost/index.php/component/k2/item/197-turning-down-glucose-metabolism-in-cells-slows-influenza-infection-suggesting-a-new-strategy-for-flu-therapy

Fischetti, M. (2014, January 3). Fact or Fiction?: Feed a Cold, Starve a Fever. Scientific American. https://www.scientificamerican.com/article/fact-or-fiction-feed-a-cold/

Henderson, G. (2014, March 13). The High-fat Hep C Diet: On Participating in a Phase III Trial of Sofosbuvir and GS-5816 for Hepatitis C [Blog]. The High-Fat Hep C Diet. https://hopefulgeranium.blogspot.com/2014/03/on-participating-in-phase-iii-trial-of.html

Kilbourne, E. D. (1959). Inhibition of Influenza Virus Multiplication with a Glucose Antimetabolite (2-deoxy-D-glucose). Nature, 183(4656), 271–272. https://doi.org/10.1038/183271b0

Kohio, H. P., & Adamson, A. L. (2013). Glycolytic Control of Vacuolar-Type Atpase Activity: A Mechanism to Regulate Influenza Viral Infection. Virology, 444(1), 301–309. https://doi.org/10.1016/j.virol.2013.06.026

Michaelis, M., Doerr, H. W., & Cinatl, J. (2009). The Story of Human Cytomegalovirus and Cancer: Increasing Evidence and Open Questions. Neoplasia (New York, N.Y.), 11(1), 1–9.

Reading, P. C., Allison, J., Crouch, E. C., & Anders, E. M. (1998). Increased Susceptibility of Diabetic Mice to Influenza Virus Infection: Compromise of Collectin-Mediated Host Defense of the Lung by Glucose? Journal of Virology, 72(8), 6884–6887. https://doi.org/10.1128/jvi.72.8.6884-6887.1998

Yu, Y., Clippinger, A. J., Pierciey, F. J., & Alwine, J. C. (2011). Viruses and Metabolism: Alterations of Glucose and Glutamine Metabolism Mediated by Human Cytomegalovirus. Advances in Virus Research, 80, 49–67. https://doi.org/10.1016/B978-0-12-385987-7.00003-8

Zeratsky, K. (2023, January 12). The Myth About Caffeine and Dehydration [Informational]. Mayo Clinic. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/caffeinated-drinks/faq-20057965