Poll

Have you tried the Niacinimide + matcha pre-pack?

Yes - followed it precisely: 100% effective (no POIS)
0 (0%)
Yes - followed it precisely: 90% effective (very mild POIS)
0 (0%)
Yes - followed it precisely: 50-90% effective or less
2 (66.7%)
Yes - followed it precisely: 0-50% effective (didn’t work)
0 (0%)
Yes - but didn’t follow precisely - leave comments on effectiveness
1 (33.3%)

Total Members Voted: 3

Author Topic: B3 + Matcha powder tea pre-pack method (still POIS free after 3 years)  (Read 38836 times)

Gino

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Hi all,

Good news - I'm 3-years [updated June 2024] into this method. Totally effective. It prevents all my POIS symptoms. Lucky to have a very good sex life:

Method: "pre-pack" taken only before sex/orgasm/'O':

- Vitamin B3 non-flush niacin (Dose: 1 x tablet of 500mg B3 nicotinamide (also known as niacinamide or non-flush niacin); Timing: 1-to-6 hours before sex; Source: https://www.chemistwarehouse.com.au/buy/21113/nature-s-own-vitamin-b3-500mg---vitamin-b---60-tablets)

PLUS

- Matcha powder tea (Dose: 1 x glass as per usual strength for your caffeine sensitivity; Timing: Immediately before sex); Source: https://www.t2tea.com/en/au/tea/100-organic-matcha-T110AI012.html)

Results:
- No POIS symptoms. This method prevents the triggering of POIS.
- Able to actively enjoy sex: a few times per week.
- Able to concentrate on complex mental tasks and play sport to high intensity levels immediately after sex and in the following days.

Important notes:
- Matcha tea is in fine powdered form. Served unfiltered in cold or hot water less than 80 Celsius (<175 F). Drink say 30 mins before O.
- This is a prevention rather than a post-O treatment. It does NOT work if taken after O.
- I avoid alcohol and meals in the hours before O.
- Watch this for info on matcha: https://www.youtube.com/watch?v=T8eml3DvncA

Additional notes about the method:
- Green/black tea and coffee were much less effective. Something about this matcha powder works differently.
- My diet: Strict gluten-free, mostly vegetarian and occasional seafood.
- When I forgot to use this pre-pack before sex I later experienced a nasal cold sore (I have had this before). This was quickly resolved with a dose of Famciclovir https://www.yourdiscountchemist.com.au/apo-famciclovir-500mg-tablets-3-famvir-generic.html
- Matcha powder tea contains much higher levels of L-theanine compared to green/black tea. This leads to a state of calm alertness, without jitters that caffeine from coffee creates.
- Therefore I assume it is the combination of matcha's caffeine and L-theanine (plus non-flush B3) that prevents the triggering of POIS.

Additional notes about my POIS:
- My usual full POIS symptoms were debilitating mental and physical types, including: immediate and continuous fatigue - mental, facial and body symptoms - all over muscle and joint tightness, weakness and aches, an all over feeling of inflammation similar to a cold or flu, chills and sweats, horrible mood swings such as agitation and anger, acute sensitivity to light, very poor decision making, short memory, inability to mentally process simple information or carry a conversation, inability to perform basic sequential tasks such as make cereal (e.g. I would often find myself putting away the spoon, bowl or milk before eating the cereal.. or pouring milk into the cereal box). These symptoms would usually last between 3-to-6 days at various intensities. My usual response was to just lie in bed in a dark room and avoid interaction with people.

 
« Last Edit: June 09, 2024, 04:56:51 AM by Gino »

Iwillbeatthis

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Re: B3 + Matcha tea with L-theanine
« Reply #1 on: March 14, 2021, 08:29:45 AM »
Nicotinamide slow release 1500mg also helps me but I haven't tried for POIS yet, have you tried having the matcha at the same time as the nicotinamide?

Iwillbeatthis

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Re: B3 + Matcha tea with L-theanine
« Reply #2 on: March 14, 2021, 08:32:15 AM »
Possible reason why Nicotinamide works

https://pubs.acs.org/doi/10.1021/acschemneuro.0c00628
This suggests that downregulating Sirt1 results in upregulated MAO-A (which is what you want). Slow release NAM (nicotinamide)  in doses of 1-2g should do that for you.
Additionally I suggest NAC slow release 1200mg to balance glutamate and reduce catecholamines"

Quantum

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Re: B3 + Matcha tea with L-theanine
« Reply #3 on: March 14, 2021, 09:08:02 AM »
Hi all,

Good news - I'm 2 months into this method and finding it to be very effective in preventing all usual symptoms and allowing for a very good sex life:

Method:
- Vitamin B3 (Dose: 1 x tablet of 500mg niacin nicotinamide; Timing: 2-to-6 hours before sex; Source: https://www.chemistwarehouse.com.au/buy/21113/nature-s-own-vitamin-b3-500mg---vitamin-b---60-tablets)
- Matcha tea (Dose: 1 x glass as per usual strength for your caffeine sensitivity; Timing: Immediately before sex); Source: https://www.t2tea.com/en/au/tea/100-organic-matcha-T110AI012.html)

Results:
- No POIS symptoms noticed immediately after sex nor in the following days.
- Able to actively enjoy sex. E.g. a few times within Mon-Fri and a few times during the weekend.
- Able to concentrate on complex mental tasks and play sport to high intensity levels immediately after sex and in the following days.

Important notes:
- The matcha tea I took includes amino acid L-theanine: "...The combo of caffeine and amino acid L-theanine in matcha buddy up to give you a slower release of energy. This means no caffeine jitters, and also means you can power on for longer."
- Must have B3 tablet and matcha tea before sex. It seems to be a prevention mechanism rather than a treatment. It doesn't work if taken after sex.
- I avoided alcohol and heavy meals in the hours before sex.

Additional notes:
- Daily tablet of Echinacea with Vitamin C. This in itself doesn't prevent POIS symptoms but I believe it reduced my symptoms in the past to a much lesser extent. https://www.chemistwarehouse.com.au/buy/57027/cenovis-echinacea,-garlic,-zinc-c---contains-vitamin-c---125-tablets
- Diet: Gluten free, mostly vegetarian and some seafood.
- In the last two months I experienced one nasal cold sore. This was quickly resolved with a dose of Famciclovir https://www.yourdiscountchemist.com.au/apo-famciclovir-500mg-tablets-3-famvir-generic.html
- I previously had some success with B3 and green tea [i.e. not the matcha type]. I found it unreliable and often needed to rest for hours after sex.
- Coffee or other teas were also unreliable regardless of dosage and usually resulted in jitters.
- My usual full POIS symptoms were mental and physical types, including: immediate and continuous fatigue - mental, facial and body symptoms - all over muscle and joint tightness, weakness and aches, an all over feeling of inflammation similar to a cold or flu, chills and sweats, horrible mood swings such as agitation and anger, acute sensitivity to light, very poor decision making, short memory, inability to mentally process simple information or carry a conversation, inability to perform basic sequential tasks such as make cereal (e.g. I would often find myself putting away the spoon, bowl or milk before eating the cereal.. or pouring milk into the cereal box). These symptoms would usually last between 3-to-6 days at various intensities. My usual response was to just lie in bed in a dark room and avoid interaction with people.

Notes for additional enjoyment:
- I've found that I can enjoy sex for up to 3 hours using this matcha tea + B3 method in combination with a desensitizing gel/spray (e.g. https://www.chemistwarehouse.com.au/buy/7920/stud-100-desensitizing-spray-for-men-12g. No POIS symptoms noticed regardless of duration of sexual activity.
- Cardiovascular stamina definitely improves sex duration and enjoyment. Routine high intensity exercises like running, gym workouts and competitive sports have really helped me out.

Hoping to report on continued effectiveness in the coming months.

Thanks, Gino, for the detailed description of your successful method!   I hope you will keep us updated with your long-term results, I will like to include your method in the POIS Type Charts if they last another month or so. 

The use of matcha/green tea is interesting.  Macha tea is more and more present on the market - even my daughter adds matcha powder regularly in her smoothies.   Green tea has been one of the first things I found to help against POIS, years ago.

Thanks for having detailed your diet change and other daily habits that may have contributed to your overall method success.

My own method is similar to yours in many ways:  https://poiscenter.com/forums/index.php?topic=2090.msg16604#msg16604

I am happy for you that you have found significant relief for your POIS!


You are 100% responsible for what you do with anything I post on this forum and of any consequence it could have for you.  Forum rule: ""Do not use POISCenter as a substitute for, or to give, medical advice" Read the remaining part at http://poiscenter.com/forums/index.php?topic=1.msg10259#msg10259

Gino

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Re: B3 + Matcha tea with L-theanine
« Reply #4 on: March 14, 2021, 10:03:22 PM »
Special shout outs to Quantum (for the B3 and empty stomach method) and Nanna1 (for recommending green tea instead of coffee when I tired the stack method).

Perhaps the matcha powder is important because its allows me to consume the full physical leaf rather than just the caffeine from a grren tea bag?

Apparently one quarter tea spoon of matcha powder is equivalent to a full teaspoon of tea or coffee.

I've been taking a quarter tea spoon with a quarter glass of boiling water. Stirring thoroughly. I consume the powder residual if it accumulates at the bottom of the glass.

It's been so easy to follow so far. I just take one B3 tablet in the afternoon and follow up with a matcha tea before any sexual activity.

If I'm not seeing my partner then I don't consume the B3 nor the matcha on that day. This is because of other's reports of the body adjusting to tolerate regular dosages of vitamins and caffiene.

Additional note: I currently consume a coffee in the morning and a diet coke with dinner. However these caffiene sources are not sufficient. So if I missed the matcha tea dose the symptoms present as usual. If I substituted matcha with coffee just before sex then I get a maybe 30% of symptom severity.

Gino

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Re: B3 + Matcha tea with L-theanine
« Reply #5 on: March 15, 2021, 03:22:56 AM »
Nicotinamide slow release 1500mg also helps me but I haven't tried for POIS yet, have you tried having the matcha at the same time as the nicotinamide?

Hi @Iwillbeatthis - yes I've tried them together in two ways:

1. As per my method, the B3 tablet (500 mg niacin nicotinamide) at least 2-hours before sex. Referring to nanna1's research, its peak effectiveness is at the 6 hour mark. Hence I take it in the afternoon if I'm likely to be sexually active in the evening.

2. I've tried the B3 tablet with matcha tea immediately before sex and it's not as effective as waiting 2-6 hours - I still experience some POIS symptoms. I will experiment with this to see if how bearable this scenario is because sometimes its not practical to take B3 so many hours in advance.

I hope that answered your question!

Gino

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Re: B3 + Matcha tea with L-theanine
« Reply #6 on: March 15, 2021, 03:28:52 AM »
Possible reason why Nicotinamide works

https://pubs.acs.org/doi/10.1021/acschemneuro.0c00628
This suggests that downregulating Sirt1 results in upregulated MAO-A (which is what you want). Slow release NAM (nicotinamide)  in doses of 1-2g should do that for you.
Additionally I suggest NAC slow release 1200mg to balance glutamate and reduce catecholamines"

Are you suggesting that B3 tablet can be substituted with "Slow release NAM (nicotinamide) in doses of 1-2g" because it has less harmful?

BoneBroth

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Re: B3 + Matcha tea with L-theanine
« Reply #7 on: March 15, 2021, 07:39:48 AM »
Does it help you from NE-POIS also? How do you take it then?


Iwillbeatthis

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Re: B3 + Matcha tea with L-theanine
« Reply #9 on: March 15, 2021, 08:03:01 AM »

Are you suggesting that B3 tablet can be substituted with "Slow release NAM (nicotinamide) in doses of 1-2g" because it has less harmful?

No it was just someone who suggested me that when I asked how to lower catecholamines with supplements. I actually want to try the normal version 500mg as the slow release doesn't work consistently and I have some issues with it.

Muon

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Re: B3 + Matcha tea with L-theanine
« Reply #10 on: March 15, 2021, 09:19:32 AM »
FYI, matcha also contains green tea catechins.

https://poiscenter.com/forums/index.php?topic=2301.msg38757#msg38757

I wonder if he affects CD38 dependent NAD+ pathways with nicotinamide. The tea could function as ROS scavenger.

Gino

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Re: B3 + Matcha tea with L-theanine
« Reply #11 on: March 15, 2021, 04:40:06 PM »
Does it help you from NE-POIS also? How do you take it then?

Hi BoneBroth. I fortunately don't experience NE so I've not had to think about this scenario. Maybe experiment in taking B3 with matcha tea at various hour ranges before usual sleep time to gauge what works?
« Last Edit: March 15, 2021, 10:00:33 PM by Gino »

Mushnikk

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Re: B3 + Matcha tea with L-theanine
« Reply #12 on: March 15, 2021, 05:48:04 PM »
The reasons behind this are possibly explained here in this thread if you search for niacin, coffeine and l-theanine: https://poiscenter.com/forums/index.php?topic=3151

drop247

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Re: B3 + Matcha tea with L-theanine
« Reply #13 on: March 19, 2021, 09:30:43 PM »
Perhaps it's time to re-examine POIS as a form of migraine. Recently I found that Niacin is used by migraine sufferers to abort a migraine before it really hits. Caffeine is also used as a remedy.

Other things that help are magnesium and taurine. It all sounds familiar.

Muon

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Re: B3 + Matcha tea with L-theanine
« Reply #14 on: March 20, 2021, 07:51:12 AM »
Perhaps it's time to re-examine POIS as a form of migraine.
You may want to take a look at Heather's case in the women's thread. We had similar discussions in the blood flow/vessel and endothelial related threads.

Muon

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Re: B3 + Matcha tea with L-theanine
« Reply #15 on: March 20, 2021, 10:28:00 AM »









ref

NO-->dopamine
https://poiscenter.com/forums/index.php?topic=3551.msg38085#msg38085

Na =nicotinic acid
NMN = Nicotinamide mononucleotide
NR = nicotinamide ribose
NAM = nicotinamide
NAD = Nicotinamide adenine dinucleotide NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD+ and NADH (H for hydrogen) respectively.
NADP+
NADPH is the reduced form of NADP+
« Last Edit: March 20, 2021, 11:49:42 AM by Muon »

Iwillbeatthis

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Re: B3 + Matcha tea with L-theanine
« Reply #16 on: March 20, 2021, 10:29:40 AM »
This combo really synergises well, I don't even feel the nicotinamide riboside much until I have the matcha tea. It seems the matcha effects are stronger when taken some hours after the nicotinamide riboside.

berlin1984

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Re: B3 + Matcha tea with L-theanine
« Reply #17 on: March 20, 2021, 03:33:52 PM »
This combo really synergises well, I don't even feel the nicotinamide riboside much until I have the matcha tea. It seems the matcha effects are stronger when taken some hours after the nicotinamide riboside.

For people reading here: nicotinamide riboside is a different form than the original poster mentioned, it's a more special thing than the B3 form mentioned.
Goes more into the NADH corner?
I wonder if there is a supplement containing all the B3 forms, if that makes any sense to get benefits in all parts of the cycle that Muon's graphic shows?


Perhaps it's time to re-examine POIS as a form of migraine.

Related:
https://en.wikipedia.org/wiki/Sexual_headache


Wolf berry

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Re: B3 + Matcha tea with L-theanine
« Reply #18 on: March 20, 2021, 09:59:41 PM »
Hi all,

Good news - I'm 2 months into this method and finding it to be very effective in preventing all usual symptoms and allowing for a very good sex life:

Method:
- Vitamin B3 (Dose: 1 x tablet of 500mg niacin nicotinamide; Timing: 2-to-6 hours before sex; Source: https://www.chemistwarehouse.com.au/buy/21113/nature-s-own-vitamin-b3-500mg---vitamin-b---60-tablets)
- Matcha tea (Dose: 1 x glass as per usual strength for your caffeine sensitivity; Timing: Immediately before sex); Source: https://www.t2tea.com/en/au/tea/100-organic-matcha-T110AI012.html)

Results:
- No POIS symptoms noticed immediately after sex nor in the following days.
- Able to actively enjoy sex. E.g. a few times within Mon-Fri and a few times during the weekend.
- Able to concentrate on complex mental tasks and play sport to high intensity levels immediately after sex and in the following days.

Important notes:
- The matcha tea I took includes amino acid L-theanine: "...The combo of caffeine and amino acid L-theanine in matcha buddy up to give you a slower release of energy. This means no caffeine jitters, and also means you can power on for longer."
- Must have B3 tablet and matcha tea before sex. It seems to be a prevention mechanism rather than a treatment. It doesn't work if taken after sex.
- I avoided alcohol and heavy meals in the hours before sex.

Additional notes:
- Daily tablet of Echinacea with Vitamin C. This in itself doesn't prevent POIS symptoms but I believe it reduced my symptoms in the past to a much lesser extent. https://www.chemistwarehouse.com.au/buy/57027/cenovis-echinacea,-garlic,-zinc-c---contains-vitamin-c---125-tablets
- Diet: Gluten free, mostly vegetarian and some seafood.
- In the last two months I experienced one nasal cold sore. This was quickly resolved with a dose of Famciclovir https://www.yourdiscountchemist.com.au/apo-famciclovir-500mg-tablets-3-famvir-generic.html
- I previously had some success with B3 and green tea [i.e. not the matcha type]. I found it unreliable and often needed to rest for hours after sex.
- Coffee or other teas were also unreliable regardless of dosage and usually resulted in jitters.
- My usual full POIS symptoms were mental and physical types, including: immediate and continuous fatigue - mental, facial and body symptoms - all over muscle and joint tightness, weakness and aches, an all over feeling of inflammation similar to a cold or flu, chills and sweats, horrible mood swings such as agitation and anger, acute sensitivity to light, very poor decision making, short memory, inability to mentally process simple information or carry a conversation, inability to perform basic sequential tasks such as make cereal (e.g. I would often find myself putting away the spoon, bowl or milk before eating the cereal.. or pouring milk into the cereal box). These symptoms would usually last between 3-to-6 days at various intensities. My usual response was to just lie in bed in a dark room and avoid interaction with people.

Notes for additional enjoyment:
- I've found that I can enjoy sex for up to 3 hours using this matcha tea + B3 method in combination with a desensitizing gel/spray (e.g. https://www.chemistwarehouse.com.au/buy/7920/stud-100-desensitizing-spray-for-men-12g. No POIS symptoms noticed regardless of duration of sexual activity.
- Cardiovascular stamina definitely improves sex duration and enjoyment. Routine high intensity exercises like running, gym workouts and competitive sports have really helped me out.

Hoping to report on continued effectiveness in the coming months.

The other alternative is to reduce histamine production using mast cell stabilisers. Histamine can also be produced by gut bacteria. If that's the problem then treating the bacteria may be the solution. Histamine can be overproduced by the body in conditions such as mastocytosis that I described earlier. In this theory niacin may help reduce the symptoms of histamine release on our cognitive functions by diverting a histamine release into our skin. Niacinamide may stabilise our mast cells.
Niacin and Niacinamide also increase levels of NAD which helps the body remove toxic metabolites of histamine and some other neurotransmitters. (called aldehydes).
GABA has a calming effect on our brains and helps us deal with excess histamine. Testosterone and steroids which reduce inflammation would help reduce the effects of an orgasm.
Methionine and various methyl donors like L-methionine, TMG and SAMe would reduce the amount of histamine over time. To do this they require b vitamins.
It's more complicated than that but there are long posts elsewhere on the forum describing the ideas. There are people who have made huge improvement in dealing with chronic fatigue syndrome by just adding NADH and/or D-Ribose. I hadn't thought of myself as chronically fatigued until I started taking NADH and D-Ribose and realised that there were lots of active things that I used to do that I had stopped because I felt tired. This is not normal for someone in their mid 30s. If you feel tired, don't want to go out etc. that's not normal and it's gotta be put right!

It wasn't always that way but this illness became worse since my late 20s and I think that has a lot to do with a decrease in hormone production and fatigue.

I think the reason why TRT works as a treatment is that POIS is actually something our body is continually fighting, which leads to inflammation and "cortisol steal". Untreated POIS would therefore naturally lower testosterone levels.  It may be viral or it may be just a genetic inefficiency but the end result is that we end up being in an "allergic" state. This does not mean that I think anyone is allergic to sperm. It's is 100% known that histamine is released during an orgasm anyway. The allergist I spoke to said she already had women patients with some allergic reactions following orgasm it's just that they're not that severe (but some suffer headaches, some get rashes, signs of nasal allergy etc.). She told me that  you don't need an allergy to sperm to produce histamine during an orgasm. A simple google confirms this.

It is also understood that the H3 histamine receptor will inhibit both histamine and the release of other neurotransmitters in the brain
This is why novel drugs like http://en.wikipedia.org/wiki/Ciproxifan are being produced that threat attention disorders &/ dementia via the H3 receptor.

It has been suggested that testosterone may inhibit the allergic reactions in men so increased testosterone may lower histaminergic reactions but the occasional orgasm related rash or flush in some men does happen. What if POIS is just that but ramped up because we have too much circulating histamine ANYWAY?

The Raising ATP and lowering Histamine path is not a quick fix by any stretch of the imagination. It's giving the body a chance to recover and assisting the body's natural healing processes by giving the cells the thing they most need to heal (energy).

Also, some interesting information and theories at http://orthomolecular.org/library/jom/1985/pdf/1985-v14n03-p162.pdf

So from reading all this I have the following ideas.
- Increasing methylation seems a very good idea but should probably be supported by b3 (or NADH) to assist in the clearing the aldehyde produced when NMH is deanimated. This should reduce POIS symptoms.
- The main cognitive symptoms may be the result of histamine causing rate limiting on neurotransmitters required for alertness via the H3 receptor action.
There is a medicinal plant called Mangosteen which may reduce PGE2 and histamine
http://www.ncbi.nlm.nih.gov/pubmed/12230104
Information on quercetin and it's anti-histamine and mast cell stabilising properties is here
http://www.bioxtract.com/plant-based-actives/quercetin/index.html

As I said before though, niacinamide stabilises mast cells, should reduce mean levels of histamine and improves aldehyde clearance by supporting a reaction with ALDH. There are lots of reasons for the POIS sufferer to consider taking niacinamide if you're not taking NADH or supplementary b3 already. I'd suggest that if you can rule out a fungal infection with your doctor then add the NADH and some D-Ribose every day. Both of those increase energy, decrease fatigue and assist a range of chemical reactions in the body.

It seems to be the most effective of the b3 forms for me anyway. A small amount (just a few mg) seems to go a huge way. Yeah, I think that we should all consider taking niacin or niacinamide daily rather than just on days where we're planning an O. This may yield a bigger long term improvement than just taking niacin on O days. Birkmayer's studies show that NADH can boost the immune system so perhaps it by itself is capable of fighting off a nasty infection but I'm not taking that chance right now. Also, there's no point in chucking down NADH after a lot of garlic as it increases stomach acid and effectively destroys the NADH. As we know, niacin promotes prostaglandin release. The flush may mitigate some PGE2 formation. Non-flush niacinamide wouldn't do this but it would tackle the underlying acetaldehyde problem better at higher dosages. Another great thing about niacinamide. If any of us do thing we have an overrun of fungus in our digestive system (candida, I'm not convinced but it does build up alcohol & acetaldehyde in people with a properly diagnosed infection...) then niacinamide is great for killing the stuff :) - Take b3 every day. niacinamide may be best to avoid daily itching (there are other reasons). Also, it may help with the cravings if you've cut down smoking to take niacinamide every day. The idea is that the problem behind POIS would exist in our bodies every day and we'd need supplementary b3 to assist us.
If you can afford it then skip the niacin and try 10mg of NADH every day. I can afford it so I'm going to continue with 10mg of ENADA NADH every day.
(Note, the ENADA stuff is coated such that it is absorbed in your colon, otherwise it's just burned in your stomach acid and it would be of no benefit). Why does niacin work?
Simply, Niacin and Niacinamide are used to make NAD which is a coenzyme used by the body to turn acetaldehyde's into non-toxic substances.
These are combined with acetaldehyde dehydrogenase to make acetaldehyde into safe acetic acid (vinegar). Some researchers have shown that supplementary niacinamide (or precursors) or indeed its related metabolised enzyme (NADH) can improve the efficiency of acetaldehyde clearance in people who have a genetic problem producing "correct" acetaldehyde dehydrogenase (the enzyme that breaks the nasty stuff down)
Why might niacin not be working for me?
You may not be taking enough. If POIS is related to aldehyde poisoning then it is an ongoing problem that is only exacerbated by the chemical cascade following an O. The problem would always exist and you'd need to take niacin or niacinamide every single day. Quantities of at least 200mg / day of niacin depending on age and the severity of POIS, at least until symptoms improve. Niacinamide may be a better option as it can be bought in time release form.

aswinpras06

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Re: B3 + Matcha tea with L-theanine
« Reply #19 on: March 20, 2021, 10:23:06 PM »
Mast cell stabilizing property of theanne and catechin when added to caffeine

https://aacijournal.biomedcentral.com/articles/10.1186/s13223-020-00502-5#citeas