Seeing Strange Effects of MSG on Blood Sugar; Anyone have an Idea What’s Going on?

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This is an update on my experiments measuring the effect of dietary supplements and low-carb foods on blood sugar.

Summary

  • A couple weeks ago, I posted an initial test of MSG on my blood glucose. Surprisingly, I saw a significant increase in the rate of rise, peak, and iAuC of my blood glucose. 
  • That was a single experiment, though, so I over the last two weeks I repeated the experiment and also tested the effect in combination with insulin.
  • The results were very consistent, with 10g MSG causing a 30 mg/dL (2x) increase in peak blood glucose over 2h. This was 3x higher than the rise observed from MSG alone.
  • Surprisingly, when I tried the same experiment, but with my standard insulin dose, the MSG had virtually no effect (there was an ~10 mg/dL drop in the first couple hours, but this was followed by a rise to the same peak and is within normal day-to-day variation). 
  • I was really surprised by these results, particularly the fact that MSG has such a drastically different effect when taken with vs. without insulin. I’m really not sure what to make of that. The only two hypotheses I can think of are:
    • MSG inhibits endogenous insulin production (leading to the higher blood glucose rise), but does not impact insulin sensitivity (and therefore doesn’t impact blood glucose in the presence of injected insulin).
    • MSG promotes gluconeogenesis when insulin concentration is low, but not when it’s higher.
  • I’m not sure how to test these hypotheses with what I have available (blood glucose meter). 

Does anyone have other hypotheses as to what might be going on or how to test it? I’m also looking for anyone who might be interested in helping me test this effect. There’s a huge range of variables here (amino acid type, quantity, protein/carb/fat ratio of the meal, whether the person has diabetes and what type). 

If you have any ideas or would like to help out, please let me know.

As always, if you have any comments, suggestions, ideas for new experiments, or want to participate, please let me know in the comments or send a PM via the contact form or to quantifieddiabetes_at_gmail.com.

Planned Experiments:

  • Baseline:
    • Glucose re-test
    • Fasting re-test
  • Low-carb foods:
    • Ketochow: Complete
    • Carbquick: Started
    • Eggs
  • Supplements:
    • Vinegar
    • MSG: this post

Preliminary Results: MSG

Figure 1.  Change in blood glucose vs. time for Ketochow + butter (blue), with MSG (orange), with my standard dose of insulin (brown), with insulin & MSG (red), and MSG alone (green).
Figure 2.  Peak blood glucose for Ketochow + butter (blue), with MSG (orange), with my standard dose of insulin (brown), with insulin & MSG (red), and MSG alone (green).
Figure 3.  iAuC for Ketochow + butter (blue), with MSG (orange), with my standard dose of insulin (brown), with insulin & MSG (red), and MSG alone (green).

Ingredient Background

Ketochow is a low-carb meal-replacement that is designed to have all the macro- and micro-nutrients you need to stay healthy. I have it for breakfast and lunch most days. It’s extremely convenient and surprisingly good. 

Butter is a solid fat source. I use it with my ketochow meals as it doesn’t mix with the powder until melted, giving the mixture excellent shelf-life.

Monosodium glutamate (MSG), is the sodium salt of glutamic acid (an amino acid). It’s primarily used in cooking as a umami flavor enhancer. It’s also been reported to reduce blood glucose when ingested along with a meal (references here). Most of the reported studies were done with high carbohydrate meals and on non-diabetics, so I was interested to test its effect with low carbohydrate meals for myself.


Procedure

Meals were prepared by mixing the specified quantities chocolate ketochow, butter, and enough hot water to reach a total volume of ~12 oz. MSG was dissolved in ~250 mL of water. Insulin was injected 20 min. prior to the meal. Blood sugar every 30 min for ~270 min. 

Quantities:

  • Control meals (labeled “ketochow + butter” or “+insulin” in graphs:
    • 54g chocolate ketochow, 28g butter
    • 54g chocolate ketochow, 56g butter
    • 54g chocolate ketochow, 56g butter
    • 54g chocolate ketochow, 56g butter, 2.25 units of Novolog insulin
  • Experimental meals (labeled “+MSG” or “+insulin, +MSG” in graphs:
    • 54g chocolate ketochow, 28g butter, 10g MSG
    • 54g chocolate ketochow, 56g butter, 10g MSG
    • 54g chocolate ketochow, 56g butter, 2.25 units of Novolog insulin, 10g MSG
  • MSG control (labeled “MSG” in graphs:
    • 10g MSG

Results

In a previous post, I reported that consumption of MSG significantly increased the rate of rise, peak, and iAuC of my blood glucose. This was really surprising, as the reported literature indicate that MSG reduces blood glucose when ingested with a meal (references here), though all studies I found were done high carbohydrate meals and on non-diabetics.

That was a single experiment, though, so I over the last two weeks I repeated the experiment and also tested the effect in combination with insulin. The results of these experiments are showing in Figures 1-3. The replicates of the previous experiments were extremely consistent: Ketochow + butter causes a consistent rise of ~30 mg/dL over ~2h, while the same meal with 10g MSG resulted in a rise of 60 mg/dL in the same time period. This is a 2x increase. 

As a control, I tested consumption of 10g MSG with no accompanying meal. This resulted in a rise of ~10 mg/dL over ~2h, only 30% of the increase caused by consuming MSG with a meal. This indicates a synergistic effect of consumption of MSG with a meal.

As a second test, I tried consuming MSG with my normal meal and insulin dose. Surprisingly, in this case the MSG had virtually no effect (there was an ~10 mg/dL drop in the first couple hours, but this was followed by a rise to the same peak and is within normal day-to-day variation). 


Discussion and Next Steps

I was really surprised by these results, particularly the fact that MSG has such a drastically different effect when taken with vs. without insulin. I’m really not sure what to make of that. The only two hypotheses I can think of are:

  • MSG inhibits endogenous insulin production (leading to the higher blood glucose rise), but does not impact insulin sensitivity (and therefore doesn’t impact blood glucose in the presence of injected insulin).
  • MSG promotes gluconeogenesis when insulin concentration is low, but not when it’s higher.

I’m not sure how to test these hypotheses with what I have available (blood glucose meter). 

Does anyone have other hypotheses as to what might be going on or how to test it? I’m also looking for anyone who might be interested in helping me test this effect. There’s a huge range of variables here (amino acid type, quantity, protein/carb/fat ratio of the meal, whether the person has diabetes and what type). If you have any ideas or would like to help out, please let me know.

While waiting to see what others think, I’m going to test the bounds of the effect. I took a huge amount of MSG, far more than is used in cooking. I’m going to evaluate smaller quantities as well as alternate amino acids to better understand the effect.


– QD


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October Blood Glucose Stats & Upcoming Experiments

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I’m about a week late on this, but here’s an update on my monthly blood glucose stats. As before, I’ll be looking at average blood glucose, coefficient of variation, and time in range

Here’s the data broken out by month:

Figure 1. Average blood glucose (blue) & coefficient of variation (orange) by month.
Figure 2. Time-in-range vs. month.
Figure 3. Time-in-range vs. month, excluding “in-range.”

No improvement vs. August. However, I had two bad sensors in September, which resulted in periodic large mismatches between my CGM and fingerstick meter. I don’t have the data to quantify the impact, but I suspect that that was responsible for a substantial fraction of the Low and High time. A quick look at the first 1.5 weeks in October shows that I’m on trend for a meaningful drop in Low (currently 3%) with no change in average glucose (still 90 mg/dL). We’ll see if it holds up.

Planned Experiments:

  • Baseline:
    • Glucose re-test
    • Fasting re-test
  • Low-carb foods:
    • Carbquick
    • Eggs
  • Supplements:
    • Vinegar
    • MSG: Preliminary tests here. I tried again, but this time while taking insulin, and saw no effect. I’m going to repeat the original test and then other variations to try to figure out what’s going on.

As always, if you have any comments, suggestions, ideas for new experiments, or want to participate, please let me know in the comments or send a PM via the contact form or to quantifieddiabetes_at_gmail.com.


– QD


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Effect of Dietary Supplements & Low Carb Foods: Ketochow, Butter, & MSG

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This post is an update on my experiments measuring the effect of dietary supplements and low-carb foods on blood sugar. This is going to be an on-going exploration. Rather than wait for complete sets of data (which would take a long time), I’m going to post each weeks worth of data as I collect it in the hopes of soliciting feedback to guide later experiments.

As always, if you have any comments, suggestions, ideas for new experiments, or want to participate, please let me know in the comments or send a PM via the contact form or to quantifieddiabetes_at_gmail.com.

Planned Experiments

  • Baseline:
    • Glucose re-test
    • Fasting re-test
  • Low-carb foods:
    • Ketochow: This post
    • Carbquick
    • Eggs
  • Supplements:
    • Vinegar
    • MSG: Started 10/2

Preliminary Results: Ketochow, Butter, & MSG

Figure 1.  Change in blood glucose vs. time for Ketochow by itself (blue) and with 28g butter (orange), 73g butter (light blue), and 28g butter + 10g MSG (red).
Figure 2.  Peak blood glucose for Ketochow by itself (blue) and with 28g butter (orange), 73g butter (light blue), and 28g butter + 10g MSG (red).
Figure 3.  iAuC for Ketochow by itself (blue) and with 28g butter (orange), 73g butter (light blue), and 28g butter + 10g MSG (red).

Ingredient Background

Ketochow is a low-carb meal-replacement that is designed to have all the macro- and micro-nutrients you need to stay healthy. I have it for breakfast and lunch most days. It’s extremely convenient and surprisingly good. I prepare 16 meals at a time and keep them in the fridge. When it’s time for a meal, I just add hot water, mix, and wait for my insulin to kick in; about 1 min. total prep. time (all-in). It also comes in 18 different flavors, so I can rotate through the ones I like and not get bored. I’ve been using Ketochow for years, so I’ve got my insulin dose pretty well tuned for it. However, following a Reddit post by Chris Bair, the owner of Ketochow on its Glycemic Index, I decided to do a detailed test of its impact on my blood sugar.

Butter is a solid fat source. I use it with my ketochow meals as it doesn’t mix with the powder until melted, giving the mixture excellent shelf-life.

Monosodium glutamate (MSG), is the sodium salt of glutamic acid (an amino acid). It’s primarily used in cooking as a umami flavor enhancer. It’s also been reported to reduce blood glucose when ingested along with a meal (references here). Most of the reported studies were done with high carbohydrate meals and on non-diabetics, so I was interested to test its effect with low carbohydrate meals for myself.


Procedure

I consumed 1.1 servings of the chocolate ketochow (54g, my normal amount) and the specified quantities of butter and MSG mixed with hot water to a total volume of ~12 oz. I then monitored my blood sugar every 30 min for ~270 min. 


Results

As shown in Figure 1, plain Ketochow shows a slow rise of ~40 mg/dL over ~2h. As discussed previously, this is similar to whey protein (the primary caloric ingredient in Ketochow is an 80:20 mix of casein & whey protein) and pretty much what you’d expect from the nutrition label and the amount of insulin I use to cover the meal.

Much more interesting is the impact of butter and MSG. The addition of butter significantly slowed the rise in blood glucose and gave an ~25% reduction in peak blood glucose and 30% reduction in iAuC. Interestingly, increasing the amount of butter from 28 to 73g did not increase the effect, though that was only a single experiment and I need to repeat it to confirm.

For MSG, in contrast to the reported literature, it significantly increased the rate of rise, peak, and iAuC of my blood glucose. This was a single experiment and I haven’t yet done the proper controls (e.g. MSG by itself), but the magnitude of the effect was much larger than I would expect from the amount of amino acid consumed, suggesting it is real. Going forward, I’m going to test MSG by itself, smaller quantities, and also combined with glucose instead of protein fat (more similar to the literature. 


Interim Thoughts and Next Steps

From this preliminary data, it looks like there are meaningful effects of combining macronutrients as well as supplements. Given that, I’m going to stick with this line of experiments. I also like this approach of posting interim data as I collect it, then writing up a more detailed report & analysis once there’s enough data to merit it.

As always, please let me know if you have any thoughts or suggestions.


– QD


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My Next Studies: Effects of Dietary Supplements & Low-carb Foods

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I’ve got my medication re-tuned and my blood sugar is much more stable, so I can start doing more interesting experiments.

Measuring the effect of different macronutrients and low-carb ingredients was really informative. In particular, I’m both fascinated and very disturbed at the huge variation in blood glucose impact of fibers that are listed identically on nutrition labels.

I’d like to continue these kind of experiments, but they were very time consuming and the frequent extended fasts were disruptive to my normal routine. To get around that, I’m going to focus on foods & supplements where I’m looking for relatively binary outcomes (i.e. large effects) and therefore can accept the larger uncertainty associated with not fasting and lower numbers of replicates.

With all that, my plan is to test the effects of popular dietary supplements and low-carb foods to see if claims about them really hold up. To avoid wasting a lot of time chasing after BS fads, I’m going to focus on supplements & foods that are either reasonably supported in the academic literature or otherwise appear to have solid data backing them up. 

Lastly, it’s widely believed that the relative blood sugar impact of foods varies from person-to-person. If you’re interested in helping me to quantify that, let me know in the comments or send a via the contact form or to quantifieddiabetes_at_gmail.com. 

Planned Experiments:

  • Baseline:
    • Glucose re-test:
    • Fasting re-test
  • Low-carb foods:
    • Ketochow: Started 9/26
    • Carbquick
    • Eggs
  • Supplements:
    • Vinegar
    • MSG

If you have any suggestions for supplements or foods to add, please let me know in the comments or send a PM via the contact form or to quantifieddiabetes_at_gmail.com.

Preliminary Results: Ketochow

I don’t want to go a week without posting any data, so here’s some preliminary results from my Ketochow experiments.

Figure 1.  Change in blood glucose vs. time for glucose (blue), whey protein (orange), and Ketochow (brown).

Ketochow is a low-carb meal-replacement that is designed to have all the macro- and micro-nutrients you need to stay healthy. I have it for breakfast and lunch most days. It’s extremely convenient and surprisingly good. I prepare 16 meals at a time and keep them in the fridge. When it’s time for a meal, I just add hot water, mix, and wait for my insulin to kick in; about 1 min. total prep. time (all-in). It also comes in 18 different flavors, so I can rotate through the ones I like and not get bored. 

I’ve been using Ketochow for years, so I’ve got my insulin dose pretty well tuned for it. However, I’ve never actually measured  it’s BG impact directly. A couple days ago, Chris Bair, the owner of Ketochow posted to Reddit about the Glycemic Index for Ketochow. You can’t do a standard glycemic index test, though, as that requires measuring the impact of an amount containing 50g of digestible carbohydrate. For Salted Caramel, that would 62 servings or 2.75 kilograms of Ketochow, which would be impossible to eat.

That said, while the blood sugar rise from carbs should be near zero, the protein should have a small effect due to gluconeogenesis. Since have Ketochow twice a day, I figured I should test it. Towards that end, I consumed 1.1 servings of the chocolate ketochow (54g, my normal amount) mixed with hot water to a total volume of ~12 oz. I then monitored my blood sugar every 15 min for ~270 min.

I’m going to run additional tests with other flavors and with fat sources added, but you can see the preliminary results in Figure 1. The Ketochow was comparable to a similar mass of whey protein, but with a slightly faster rise. This is consistent with the bulk of the macros coming from protein and dietary fiber. 

All-in-all, pretty much what you’d expect from the nutrition label and the fact that I need such a small amount of insulin to cover the meal. Someone without diabetes would almost certainly not be able to observe and blood sugar impact at all.


– QD


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Does Vitamin C Really Cause False Blood Glucose Readings? Not at an Amount I can Eat.

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Disclaimer: This experiment was only done on one person (myself) and is not fully randomized, placebo controlled, or blinded. Please take all conclusions with the appropriate skepticism.


Summary

Vitamin C is reported to falsely raise blood glucose readings in both fingerstick and continuous glucometers. I wanted to know if this was something that I (and others) should be concerned about, but all the reports I found were for intravenous vitamin C and I couldn’t get any data from the CGM companies. 

To get an answer, I tested it myself, monitoring blood glucose after ingesting 2-6g of vitamin C, 20-60 the FDA recommended daily amount (but known to be safe). I did not observe any consistent or sustained increase in blood glucose, so I conclude that ingested vitamin C has no measurable impact on my blood glucose measurements at any practical quantity.


Details

Background

When I first tried out the FreeStyle Libre CGM, I read through the manual and noticed an unusual warning:

“Taking ascorbic acid (vitamin C) while wearing the Sensor may falsely raise Sensor glucose readings. Taking salicylic acid (used in some pain relievers such as aspirin and some skin care products) may slightly lower Sensor glucose readings. The level of inaccuracy depends on the amount of the interfering substance active in the body.”

Vitamin C is an essential nutrient and present in tons of foods and most multivitamins. If it falsely raises glucose readings, that’s a huge flaw in the device.

I tried contacting Abbot, who confirmed that vitamin C can cause erroneously high glucose readings, but couldn’t point me to any studies or say how strong the effect was. I also contacted Dexcom and there support rep. said that “Vitamin C was not contraindicated for Dexcom CGMs,” but again couldn’t point me to any studies or say if they had or hadn’t run any tests.

Having failed at getting useful info directly from the CGM companies, I turned to the published literature. I found a number of reports of Vitamin C leading to high blood glucose readings (1, 23, 4, 5; not exhaustive, there are many more). From these, I learned the following:

  • All reports in scientific or medical journals were for patients taking intravenous vitamin C.
  • Vitamin C can be oxidized by glucose oxidase and glucose dehydrogenase, the enzymes used to detect glucose in most portable glucometers, including most fingerstick meters and both the FreeStyle Libre and Dexcom CGMs
  • The increase in reported blood glucose can be extremely large; in one case a women read 343 mg/dL on standard glucometer, while a blood test showed her actual blood glucose as 49 mg/dL.
  • The blood levels of vitamin C in these reports were extremely high, 1,000 – 5,000 µmol/L. This is much higher than the 100-200 µmol/L observed with regular oral vitamins.
  • There’s only one anecdotal report on a diabetes forum of someone who saw high CGM readings after taking oral vitamin C, with numerous comments from people claiming that they do not see this.

Given all this, it seemed unlikely that regular consumption of vitamin C would significantly affect blood glucose readings, but I was left with two questions:

  • Was there any measurable effect of ingested vitamin C, even if small?
  • Would mega-doses of vitamin C have a significant effect?
    • mega-doses of vitamin C were advocated by Linus Pauling (nobel prize winner in chemistry). His theory has since been debunked, but is unfortunately still used by many people.

Since I couldn’t find any direct studies of the effect of ingested vitamin C, I decided to do my own experiment. 


Purpose

To quantify the effect of ingestion of vitamin C in blood glucose readings from Dexcom G6 and Freestyle Libre CGMs.


Design/Methods

Procedure. At selected times of day, 2, 4, or 6g of vitamin C was ingested and blood glucose monitored using a continuous glucose monitor.

Measurements. Blood glucose was measured using a Dexcom G6 CGM and FreeStyle Libre 14 day CGM.

Data Processing & Visualization. Data was visualized using Tableau.

Medication. I took my normal morning, evening, and meal medications


Data

set1, set2


Results & Discussion

Figure 1. Blood Glucose vs. time for each of four vitamin C ingestion experiments. Color represents data from Dexcom G6 (blue) and FreeStyle Libre (orange)

According to the NIH, the recommended amount of vitamin C is 65-90 mg/day and the tolerable upper limit is 2,000 mg/day. However, studies have shown no serious adverse effects at much higher amounts and >10,000 mg/day is prescribed for treatment of certain cancers with no ill effects. Given that information, I tested ingestion of 2,000, 4,000, and 6,000 mg of vitamin C. 

As can be seen in Figure 1, there was no significant rise in measured blood glucose in any of the four experiments that could be attributed to vitamin C intake. While here were transient increases in measured blood glucose in the first three measurements, they were not consistent in time or magnitude. In addition, all the reports of increases from intravenous vitamin C indicated that the effect was of long-duration (such that measured blood glucose was still elevated well after the patient arrived at the hospital or clinic). 

Based on this data and the fact that typical vitamin C consumption is much less than what I took in these experiments, I conclude that ingested vitamin C has no measurable impact on blood glucose measurements at any practical quantity.


Final Thoughts & Next Experiments

This was a very satisfying experiment. Pretty quick, answered a question I wasn’t able to find in the literature or from the CGM companies (though they probably knew the answer), and results were very clear. 

Next up:

  • Re-tune basal and bolus (meal) insulin doses
    • My routine has changed a lot due to working from home, changing doctors, and changing medication (due to insurance requirements). Plus, I was able to get a Dexcom G6 CGM, which is showing accuracy comparable to my blood glucose meter. Blood sugars are still good, but I think I can get them better.
    • This is going pretty well. As I expected, I had my basal:bolus ratio off. I’m steadily getting it corrected and it’s making my blood sugar a lot more stable.
  • Re-measure blood sugar impact of glucose and insulin; compare to previous data
    • While working from home, I’ve gained some weight (and hopefully muscle). This has resulted in a change in my insulin sensitivity. Not huge, but I need to remeasure to have an accurate baseline for future experiments.
  • Test the effect of some dietary supplements that have been reported to affect blood sugar in the literature, but where data insufficient or contradictory
    • Glutamate (reported to reduce post-prandial glucose, but magnitude and timing vary widely)
    • Others tbd. 

As always, if you have any questions, comments, suggestions, or are interested in joining in future experiments, please let me know in the comments or send a PM via the contact form or to quantifieddiabetes_at_gmail.com.


– QD


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