Melatonin to Stay Asleep Longer: Protocol & Pre-registered Analyses

Summary

I’m trying to sleep longer, but am waking up too early in the morning. I’m going to test if melatonin can help me sleep longer. Based on suggestions solicited from the ACX open thread, I’m going to try a 30 day, blinded, randomized trial of 0.3 & 3 mg melatonin, both regular and extended release. If I see anything promising from this initial test, I’ll repeat the trial with the best condition to confirm and get a better measure of effect size.

Details

Purpose

To determine if taking melatonin supplements in the evening extends the duration of my time asleep and subjective fatigue given a consistent bedtime.
To determine if taking melatonin supplement and/or sleeping longer affects subjective fatigue, blood glucose, heart rate variability, or pulse

Background

Over the past 5 weeks, I’ve been making an effort to get more sleep. I’ve been able to hit an average time asleep of ~7h and, qualitatively, I’ve been feeling a lot less tired and have been able to concentrate better in the afternoons.

I’d like to see if sleeping even longer will result in further improvement. However, over the last week I’ve noticed that I’ve been waking up earlier and earlier (before my morning alarm). I stay in bed (eyes closed) until the alarm, but can’t go back to sleep.

Based on my data so far, there’s no clear correlation with time I fell asleep or total time asleep. Might be a correlation with heart rate variability, but I need more data to be sure.

I’d like to test some interventions to sleep longer. I already exercise in the evenings and for as long as I’m willing to do (~30 min. high intensity, 5-10 min. stretching), my last meal is 4h before going to bed, and my CGM does not show a consistent rise in blood sugar before waking up.

Given that, my next thought was to try melatonin. It’s typically used to control when you go to sleep, but it last long enough in the bloodstream that it might impact time asleep as well. Based on suggestions solicited from the ACX open thread, I’m going to try a 30 day, blinded, randomized trial of 0.3 & 3 mg melatonin, both regular and extended release. If I see anything promising from this initial test, I’ll repeat the trial with the best condition to confirm and get a better measure of effect size.

Methods

Materials

Melatonin (I couldn’t find a single supplier for all types):
- 0.3 mg – Nootropics Depot Melatonin Capsules
- 3 mg – Nature Made Melatonin
- 0.3 mg, extended release – Life Extension Melatonin 6 Hour Time Released
- 3 mg, extended release – Douglas Laboratories Melatonin PR
Gel Capsules: XPRS Nutra Size 000 Empty Capsules (Red/Black)

Blinding

Melatonin was placed in opaque, size 000 gel capsules (6 per type).
Dosages were randomly assigned to days using the excel random number generator and placed into a coded pill container by a second person (not me).
Data will be unblinded after the completion of the experiment.

Procedure

At 9pm, I will take that days gel capsule with minimal water.
At 9:30pm, I will turn lights off and attempt to go to sleep.
I will record:
- If I wake up during the night
- Subjective tiredness (1-3 scale) upon arising and at 3p
- If any other unusual events occur

Measurements

Sleep, HRV, & pulse: Apple Watch Series 5 + Autosleep app
Glucose: Dexcom G6 CGM
Blood pressure (weekly): Omron 10

Analysis

Sleep time, wake time, total time asleep, number of times waking up before alarm, fasting blood glucose, time of morning blood glucose rise, pulse, and HRV will be plotted vs. dose and release type.
p-values will be calculated for each comparison and corrected for multiple-comparison
Additional exploratory analysis may be done based on the data, but will be noted as such

Data Processing & Visualization

Data was exported from Autosleep, reformatted using a custom python script, and visualized using Tableau. Wake times were corrected manually using contemporaneous notes (see measurements, above).

Data

All data will be posted after it is unblinded.

Results & Discussion

Results will be posted and discussed after the data is unblinded and analyzed.

Conclusions & Next Experiments

Conclusions & next experiments will be posted after the data is unblinded and analyzed.

– QD

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Please Critique my Experiment Design: Self-Experiment to Sleep Longer

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Summary: I’m trying to sleep longer, but am waking up too early in the morning. I’d like to test some interventions to sleep longer (including melatonin) and am looking for advice.

Based on my data so far, there’s no clear correlation with time I fell asleep or total time asleep. Might be a correlation with heart rate variability, but I need more data to be sure.

The only thought I had was to try melatonin. It’s typically used to control when you go to sleep, but it last long enough in the bloodstream that it might impact time asleep as well.

Plan:

Self-blinded study using melatonin placed inside placebo capsules
Concentrations: 0, 0.3, 3 mg (random assignment)
Duration: 4 weeks

Questions:

Anyone else have the same problem? What has worked for you to sleep later?
Any other suggestions for interventions to try?
Any comments or critiques on the melatonin experimental design?
- Is random assignment by day sufficient or do I need to block by a longer time period, use washout days, etc.?

– QD

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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

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).

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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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.

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.

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).

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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