Hello friend,

“Why on earth would you search for a drug to reduce glucose?”, you may ask.

Well, well, well, young disciple…
The reason is very simple and yet very, very complex:
to justify eating ice-cream, for the sake of science.
For that, young warlock, is the purpose of life. Anyway..

“So, what’s Berberine then?” Berberine is a plant-extract that has been shown in both human and animal trials to be as effective as pharmaceuticals for treating type-II diabetes. Unfortunately, all the clinical trials I could find only showed how it reduced biomarkers of diabetes, such as fasting blood glucose and HbA1c, but none showed the actual trend after ingesting a meal. This, you may have guessed is important on the days you want to have the upsides of pizza, with none of the downsides.

So I decided to try it home instead. The result? It exceeded my expectations.

How the experiment went

• Every day at the same time I took 150g of cooked rice (that is about 45g of carbohydrates).

• To measure my glucose, I used a continuous glucose monitoring (CGM) and analyzed my data using glyco in Python.

• Most trials use a dose of 0.5g of Berberine, 3 times a day. Instead I took a dose of 2g in one meal. Go big or go home, right?

• I either took the Berberine or a placebo (used Berberine-500 from Thorne Research). And I either took them 15min before or right after a meal. I sat down for 2hours after the meal, and avoided exercise and food before the rice meal.

Results: how Berberine exceeded my expectations

As you can see in Fig. 1, you don’t need statistics to see how big of an impact it has on glucose. When taken 15min before the meal, Berberine largely reduced my peak glucose, but also the area under the curve of glucose. The effect was so large I could guess that I did not have placebo that time.

This should not be surprising given the large body of evidence supporting Berberine, including mechanistic evidence about how it indirectly activates AMPK [Brusq et Al. 2006]. But seeing it in real-time using the CGM left me stunned. I looked at the data, looked back at the empty bowl, looked back at the data, I could not believe it.

I have to admit, however, that I stopped the experiment early. While the original plan was to do this for 10 days, ingesting 150g of rice made both my heart-rate and blood pressure go up.

For this reason, I was worried the effect might have been due to something else (you never know ¯\_(ツ)_/¯). So I tried again, this time with a snack bar that has about 15g of carbohydrates. And once again, the drug did the job (Fig. 2 below).

As skeptical as I was at the beginning of this experiment, these results were not only convincing, but impressive.
I am now officially a Ber-believer. Yes, yes, I just made that up.

Discussion: Why I don’t use Berberine daily

After seeing the dramatic effect on glucose, I still do not to use it everyday. Instead, I would probably use it when exposed to high amounts of glucose in parties or other uncontrolled high-carb high-GI scenarios.

Other than the extra 2$/meal it would cost, there are two more reasons why I would not use Berberine everyday:

1. When I take Berberine, my glucose drops (Fig. 3 below). This drop is so abrupt that I feel tired afterwards. This feeling was worse when consumed in a fasted state.

2. In the world of supplements, there is no such a thing as a free lunch, and the risks of taking a supplement must always be weighed against the risk of not taking it. And in this scenario, I think staying relatively low-carb is a better strategy.

3. Don’t try using Berberine as a powder in ice-cream. The taste is not worth it (and believe me, my taste is as stoic as it gets) and it will turn your teeth yellow (unless that’s the style you’re going for).

For those of you who skip directly to the end of this article

Here’s the summary: Berberine largely reduced my glucose levels after a high-carb meal. It is now an essential supplement in my ice-cream emergency cupboard, but I would rather avoid it in regular days and just stick to lowering carbohydrates in general.

Thank you for reading, if you liked this post, please give it some claps, it’s easy but it would mean a lot to me.

Hi,
I’m Ismail and I have a confession to make…
I take sauna baths… a lot of sauna baths.
Some days, I also have a sensor stuck to my left arm.
Other days I prick my fingers.

What do these things have in common?
Well, apart from them sounding like a form of self-torture, they’re also a form of self-experimentation with the same goal in mind: keeping blood sugar levels under control.

But why care about glucose?
To keep it short, if you want to perform better physically and mentally or just want to feel great, regulating blood glucose is among the 20% of things to focus on that give you the 80% of the outcome. For example, a study published in the Diabetes Care Journal found that during acute hypoglycemia (low blood glucose): speed of information processing, working memory and some aspects of attention were impaired. On the other hand, during hyperglycemia (high blood glucose) the subjects were significantly more dysphoric, had reduced energetic arousal, and had an increase in both sadness and anxiety. So, if we truly care either about feeling good, limiting negative feelings and increasing both mental and physical performance managing glucose swings seems to be not just impactful but necessary.

So who’s this post for?
I strongly believe that the protocols mentioned in this post are worth a closer look as upgrades in the toolbox of a lot of people, from elite athletes to those of us who want to perform better, or just feel better, during most days.
It could also be useful if you want to perform beyond your current level. For example, improving glucose variability can help athletes break through their endurance threshold (a lot of which would dramatically call the “wall”) by enabling them to use less glycogen from the muscles.

The goal of this post is to go through strategies that go beyond just diet, sleep and exercise to do that.

A word of caution:

Heat can be seriously dangerous
I am not a doctor nor an expert of any kind so please don’t be dumb and consult with a health care professional before doing anything described in this post (full disclaimer at the bottom of the page).
This post will talk about the benefits of sauna bathing, it is good to know beforehand that heat can be seriously dangerous and people can die from excessive heat. Sauna use during pregnancy may carry some health risks to a developing fetus. Please take the disclaimer at the bottom of this page seriously.

Why go beyond diet sleep and exercise?

You just cannot beat diet, sleep and exercise.
Although the goal of this post is to go through uncommon methods for controlling blood glucose levels, we cannot do better than: eating well, sleeping well, and exercising regularly.

While it is clear how diet and exercise can impact glucose. Sleep still seems a little underrated. In my own case, a lack of sleep (especially for extended periods of time) seems to correlate with high morning blood glucose. Just like the example in the picture below, this seems to hold even when my diet is all under control:

Running a controlled experiment on this would not be a good idea, but this result is far from surprising. In a study that investigated the effect of sleep debt on metabolic and endocrine functions there was a clear consistent impairment of how the participants tolerate glucose when they were in sleep debt (the rate at which sugar was cleared, after injection, was about 40% slower in sleep-debt than in the sleep-recovery).

But what if we keep those above variables (meaning sleep, diet and exercise) under control and you want to go a step further? Even if those last variables are the 20% that give you the 80% of the outcome. Our goal here is to go beyond that and reach the final 99%.
Plus, some days you just want to have cake, other days you just have to wake up earlier. What can you do then to feel good and manage the day? How can you have your cake and eat it too?

So let’s get started. And feel free to tell me which tools you use in the comments.

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1) Take a sauna

In general, heat is uncomfortable. After all, cooling fans disappear from supermarkets during hot seasons and people take refuge in air conditioned shops.

That said, it appears that increasing your core temperature for short bursts is good for general health. More than just aiding with glucose control, heat stress can also drastically aid performance, increase muscular hypertrophy, endurance and cognition.

When it comes to saunas I might be a little biased. I usually take enough saunas during the week to get comments such as: watch out, you’ll end up like a dry sponge at some point.
At some point though, I tried wearing a continuous glucose monitor during sauna sessions. I noticed the following:
 — my glucose levels seem to rise during the sauna usage.
 — after the session is done my glucose levels stabilize to a lower value than they were before.

Note that it is possible that this spike is caused by a problem in the sensor’s measurement due to the heat or dehydration. Even if that were true, the levels of glucose seem to stabilize to a lower level than usual. A study on dry saunas, published in the British Medical Journal, showed that: taking a sauna accelerated the uptake of insulin (a hormone that regulates glucose). This uptake, also favors skeletal muscle, which gives an explanation to the raise in hypertrophy with the use of saunas. A study on mice suggests that the reason muscle tissue is favored, instead of adipose tissue (or fat), is caused by an increase in the expression of a type of transporter known as GLUT-4 (responsible for transporting glucose from the blood into skeletal muscle). This is also possibly one of the reasons why heat acclimation has been shown to reduce the usage of muscle glycogen by about 40% to 50%, in addition to the increased flow of blood to the muscles.

Once again, saunas and heat exposure come with risks. Please read the disclaimer at the end of this article.

How to implement this:
—Most days when possible because saunas are awesome.
—In the morning after a night of non-optimal sleep
— After having had a large meal, waiting two hours or more to avoid going there with a full stomach.

2) Go for a walk, use a standing desk

As simple as the title suggests, especially after having a meal with my co-workers I would usually:

• Go for a walk.

• Use a standing desk.

I wish I had a treadmill desk so I could do both in the same time.

Note that this is not just about reducing glucose through the energy demands from standing or walking. It’s about keeping those levels stable. For example, in an office-based study published in the journal of Occupational and Environmental Medicine, working in a standing position seems to reduce spike in blood glucose by about 43% (compared to sitting for the same amount of time).

That said, some days I do sit for a long time either because I am focused on something, because I am on a meeting or just because I straight out do not want to. The key here is making sure those days are the exception not the rule.

How to implement this:
—Going for a walk after lunch at work, or after dinner.
—Using a standing desk during the day, when possible.

3) Eating bitter plants, herbs and spices

Of all the previous advice this one is probably the easiest. And the reason is because it tastes good. Before meals, including things such as: cinnamon, apple cider vinegar, lemon juice, or bitter melon can also be a way to keep stable levels of glucose. And if it is still early enough, green tea before or after meals can also increase insulin sensitivity and the uptake of glucose into the cells. That said, I have not done any controlled experiment to verify if these actually have an impact on how my glucose levels fluctuate.

But here’s the thing: there is enough evidence to support those compounds and they’re tasty anyway!

Ceylon Cinnamon, for example, is not only tasty but also seems to increase insulin sensitivity, and getting more glucose from the blood into cells. The other good news is, taking about 2 teaspoons a day would be enough you and do not need to ingest a whole cup or go through the cinnamon challenge to get those benefits. For example, In a randomized controlled trial, healthy individuals supplemented with either 5g of cinnamon or 5g of placebo. Consuming just 5g of cinnamon seems to reduce total plasma glucose responses to glucose with effects lasting up to twelve hours. A meta analysis shows that cinnamon also improves fasting blood glucose, total cholesterol, triglycerides and other biomarkers. So no need to wait for pumpkin spice season to use cinnamon.

Another plant extract that is worth mentioning is Berberine. When it comes to reducing blood glucose, a large number of studies suggests that the usage of berberine rivals oral hypoglycemic drugs such as Metformin in its effectiveness. Berberine seems to indirectly activate an enzyme known as AMPK while inhibiting PTP1B. As a result, this would increase the uptake of both carbs and fats into cells from the blood. However, I have not used Berberine myself because I am still skeptical about how it works on the molecular level and because most of the evidence comes from studies targeting individuals with type 2 diabetes. Please note that Berberine is known to inhibit the activity of certain enzymes which can lead to a host of drug interactions and that high doses can cause cramping and running pants.

I’ll personally stick with my Cinnamon on this one.

How to implement this:
—Adding bitters with food or before having a meal.
—Drinking green tea if it’s not late yet.

4 ) Using exercise throughout the day

By this I mean:

• exercising in a fasted state, before having any food.

• Taking small exercise breaks throughout the whole day instead of one hour of exercise (usually referred to as greasing the groove).

A study on the effects of fasted exercise (exercising before breakfast) suggests that exercising in a fasted state is better than exercising in a fed state in improving the tolerance to glucose and insulin sensitivity, in addition to facilitating muscle adaptations.

On the other hand, taking small exercise breaks during the day not only allows you to become proficient at certain movements (such as pull-ups, squats or dead-lifts), it also keeps your metabolism elevated throughout the day and frees you from the need of setting time for structured workouts.

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Important Disclaimer:
This post is for informational purposes only.
The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. You must consult with a health-care practitioner, before undertaking any of the exercises, habits, protocols, techniques or otherwise described herein.
This blog does not constitute the practice of medicine or any other professional health care services, including providing medical advice. The use of information on this post is at the user’s own risk. The author expressly disclaims responsibility for any adverse effects that may result from the use or application of the information contained herein.

Control blood glucose with these uncommon ways was originally published in Biohacker Blog on Medium, where people are continuing the conversation by highlighting and responding to this story.

Time for another experiment. And this time it’s about sleep.

I have been using oral GABA to go faster to sleep. But I wasn’t sure it really helped. This is because the days I used GABA were days when I had trouble getting to sleep anyway, which made it hard to tell if GABA had any effect. So I decided to run an experiment and compare it to placebo.

After this experiment, I stopped using GABA as a supplement, and you will understand why in the results.

The form of GABA naturally present in the brain, Gamma-Aminobutyric Acid, is well established as an amino acid that supports in reducing stress, and enhancing sleep. But, using GABA as a supplement is not the same. Several human clinical trials have been conducted, results regarding the role of natural and/or biosynthetic oral GABA intake on stress and sleep seem to be mixed.

Summary of the results: GABA did not meet my expectations

I was expecting increased deep sleep, and total sleep, with GABA, but that did not seem to be the case. The results were:
➜ Less deep sleep compared to placebo, as measured by the Oura ring.
➜ Faster sleep compared to placebo, as measured by the Oura ring.
➜ Subjective feelings of drowsiness compared to placebo.

Note that the experiment is too small to truly make any conclusions on the statistical significance of the results.
That is why I stopped taking GABA for the purpose of enhancing sleep, but I still think there is potential for the use of GABA as a supplement for other purposes or in a different form than the existing supplements.

PS: if you’re interested in self-experimentation or want to get updates about the experiments I’m running feel free to join my mailing list here: https://ismail.bio/subscribe

Method: How I took the GABA supplement

How much GABA I took and how much time did it take to get a result.

• Which GABA supplement I took: Thorne’s PharmaGABA-100 supplement
  (note that this also contains: Calcium Laurate, Hypromellose Capsule, Magnesium Citrate and Microcrystalline Cellulose)

• How much GABA: 2 capsules with 100mg of GABA each (200mg in total).

• Placebo: I used acacia fiber as placebo. 2 x capsules on Placebo days.

• Blinding: I had a friend place the Placebo pills and GABA pills in similar jars, label them as A and B, and keep which one is A and which one is B under the jars (in a way that I could not see them). And for some extra “double blinding”, I did not check the meaning of A and B until I was done with the analysis. When this was done, I replaced the values in the visualisations below (GABA ended up being A, and Placebo being B).

• Timing: I took GABA 15min before going to bed.

Results

Before discussing the main results, it is good to note that there was no difference in bedtime and total sleep time in both experiments. The main results were that on days I used GABA, my deep sleep seems to be lower while it still seemed like I went faster to sleep.

Lower deep sleep with GABA supplementation

The first result that surprised me was that my deep sleep seemed lower with GABA intake. This goes contrary to a lot of the research that claims that GABA supplementation increases deep non-rem sleep. However as discussed in a systematic review [Hepsomali et al. 2020] the GABA supplementation studies fail to show any beneficial effect of GABA intake other than sleep latency (if at all).

The graphs here do not show statistical significance, but they give a better idea of how much difference there was between GABA and placebo.

Interpretation: why GABA may reduce deep sleep

I suspect this is due to the fact that after taking in GABA only increases plasma levels of GABA the first couple of minutes and then causes lower levels than the original baseline.

• ~30 minutes after supplementation: rapid increase of plasma GABA concentration. This may be responsible for the reduction in sleep latency.

• ~60 minutes after supplementation: a rapid decrease of plasma GABA concentration which may explain a lowering of deep sleep.

Faster to sleep with GABA

On the upside, I was getting faster to sleep with GABA. While as you can see there is an outlier value where it shows much longer, but even when this outlier is taken away (figure in the middle) it still seems that I slept faster with GABA.

This is consistent with my subjective feeling, with existing research and with the interpretation above.

Would I sacrifice deep sleep over faster sleep? It feels tempting, but most of the time I would prefer not to do that. Especially when there are other alternatives.

Possible confounding factors

Other things may have interfered with this self-experiment.

It is possible that my sleep on a weekend day is different from the rest of the weekdays. This experiment was only 12 days long, so we should check how the weekends and weekdays were split between GABA days and Placebo days.

As you can see, weekends consisted mostly of Placebo days, whereas weekdays consisted mostly of GABA days. It is possible that the results we saw earlier were impacted by that. In other words, that my deep sleep seemed longer during a Placebo day just because it was a weekend.

Without doing any complex statistics, the relationship between deep sleep and weekend/weekdays did not seem as high as the relationship between GABA and Placebo.

As I mentioned earlier, the following variables did not seem to differ : bedtime, wake-up time had no difference, neither did total time in bed. I also compared subjective measures of exercise intensity as these can also have an effect, but there was no major difference.

Conclusion

In this case both my gut feeling and the emotionless data agreed, and I stopped taking GABA.

This shows the benefit of experimenting yourself and not basing everything on existing research. What works for most people, does not work for a few people, and you may be part of the few people. Remember that this does not mean no one would benefit from GABA supplementation. If anything, there probably are a lot of people who would.

This experiment could be improved if it lasts about 28 days and if we design it to take into account all the possible confounding factors (exercise, weekends etc.).

If you have done any statistics in the past, you will know that this visual analysis is not enough to make any conclusions. But if you have done any self-experimentation, you would also understand that there is a sweet spot between what is statistically relevant and keeping your sanity.