Around the world, people are searching online for Agmatine stacks and how to use this powerful neurotransmitter supplement together with Kratom. In this article, we look into how to use Agmatine to help with Kratom tolerance, as well as some of the other top Agmatine stacks.
Agmatine itself is often used in pre-workout stacks to boost energy levels and physical performance. It is also effective at reducing stress, supporting a healthy mood, and has neuroprotective and cardioprotective benefits too. It’s one of our favourite health-promoting supplements and may also help to support healthy cognition and memory.
What is Kratom?
Kratom (Mitragyna speciosa) is a tropical plant that is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea. It has been used in traditional medicine in Southeast Asia for centuries.[1]
At low serving sizes, Kratom is said to have energizing and alertness-enhancing effects, while larger servings are used for calming, relaxation, and pain relief.
Although Kratom is beneficial to most people who use it, it can cause problems if it is misused. When taken in excess, Kratom stimulates receptors in the brain called opioid receptors. These receptors are also the targets for certain pain-relief medications as well as a number of illicit substances.[2]
As with all compounds that stimulate opioid receptors, too much Kratom can cause respiratory depression (slow, shallow breathing). When combined with alcohol or other sedatives, this can be very dangerous to your health. A number of deaths have been linked to Kratom, but almost always when combined with alcohol or opioid medication.[3]
Daily use of Kratom can cause tolerance to build fairly quickly. This means that a larger serving is required to experience the same effects as before. Naturally, this comes with a greater risk of adverse effects. Furthermore, once tolerance has developed, if you stop using Kratom right away, you may be in for a nasty, and dangerous surprise – known as Kratom withdrawal.[4]
Why Take Agmatine with Kratom?
Although there is not yet any research published on the combination of Agmatine and Kratom, animal studies and anecdotal reports from the internet indicate a positive relationship.
In one study, researchers examined the effects of Kratom on dependence and tolerance to morphine, in mice. The results showed that Agmatine not only blocked the development of tolerance but also increased the pain-relief effects by a factor of 3.[5]
Clearly, this is a very interesting relationship that might even extend to other pain-relief substances (including Kratom). However, more research is needed to properly understand these effects and how they might work in humans.
In one online forum, a Kratom user posted his experience combining with Agmatine:
“…1.5g now achieves the same effect as 3g for me and is perhaps still too much. All I did was add agmatine. It’s got a long half-life of what I think might be 10 hours where it exerts its actual effect on NMDA receptors…”[6]
On another forum, a user posted a similar experience:
“Twice today I tried 500 mg of agmatine sulfate 30 min before burning kratom… With the NGSMD it made it more uplifting with slightly more enjoyment. This evening with the RHB I am feeling quite content and have a feeling of well-being… Agmatine is supposed to reduce tolerance and I think it just may.”[7]
There appears to be at least a moderate positive relationship between the two, with Agmatine improving the effects of Kratom, reducing the required amount to feel desirable effects, and thereby decreasing the risk of developing tolerance.
Other Agmatine Supplement Stacks:
Apart from Agmatine with Kratom, people also search for other supplement stacks to synergize this great substance. We’ve listed a few of our favourites below:
1. Agmatine with Creatine
Creatine is one of the best-researched supplements in the world. It is known to help with energy levels and to boost physical performance during exercise.[8]
Creatine is a high-energy compound produced in the human body as phosphocreatine. This compound releases energy in cells to protect against stress. Creatine has additional protective effects on the brain, heart, liver, and bones. It may help to improve muscle gain for bodybuilders, and helps muscles to retain water.[9]
The combination of Agmatine and creatine is great for anyone looking for a high-performance pre-workout supplement stack. Both these supplements are known for their energy-boosting effects and their ability to support healthy exercise performance and cognition.
However, there is one thing to remember – creatine and Agmatine have opposite effects on NMDA receptors in the brain (see: How Agmatine Works). According to the supplement’s information page, Examine.com, these two supplements shouldn’t be taken at the same time if it’s the cognitive effects that you’re after.
However, taking them together is still effective for muscle building and athletic performance. You could also split the servings – i.e. Agmatine in the morning, creatine in the evening.
| Agmatine Sulfate | Creatine Phosphate |
| + Supports physical energy levels | + Improves physical energy levels and exercise performance |
| + Helps to reduce sensations of pain | + Supports muscle gain |
| + Promotes a healthy mood | + Reduces fatigue |
2. Agmatine with Caffeine
Caffeine is arguably the most important energizing substance known to man, simply because of its prevalence around the world. An estimated 80% of Americans start their day with a cup of coffee.
By the way – have you heard about combining Caffeine with L-Theanine? Check out our blog post on this great supplement stack here: Caffeine with Theanine.
In one animal study, researchers examined the effects of combining Agmatine with caffeine. They found that Agmatine blocked some of the locomotor-stimulant like effects of caffeine, in male mice (but not in female mice).[10]
This combination hasn’t been studied in humans, but there is some anecdotal evidence that Agmatine may increase the energizing effects of Caffeine.[11] It’s a supplement stack that’s definitely worth trying. In terms of biochemical effects, both Agmatine[12] and caffeine[13] work as antagonists of NMDA receptors, which strengthens the argument for a synergistic relationship.
| Agmatine Sulfate | Caffeine |
| + Supports healthy cognition | + Improves energy levels and wakefulness |
| + Helps to support healthy blood pressure | + Boosts mood |
| + Reduces feelings of stress | – Can cause mild anxiety |
3. Agmatine with L-Citrulline / L-Arginine
In the human body, Agmatine is synthesized from L-Arginine, an amino acid which, itself, is synthesized from L-Citrulline. These amino acids are typically included in protein shakes, often used by athletes or bodybuilders.
L-Arginine is a conditionally essential amino acid. It is important for maintaining healthy blood flow by directly stimulating nitric oxide production in the body. It is sometimes used as a dietary supplement to support exercise performance but unfortunately does not have very good absorption into the bloodstream.[14]
L-Citrulline is an amino acid sometimes used as a sports performance and cardiovascular health supplement. Studies have shown that Citrulline reduces fatigue and improves exercise performance, and may boost physical power output. It has better absorption and efficacy than L-Arginine supplements.[15]
According to Examine.com, Agmatine does not go well with either L-Citrulline or with L-Arginine. The reason is that L-Citrulline and L-Arginine compete with Agmatine at some brain receptor sites, and can diminish its beneficial effects.[16]
As a result, it is actually better to not take Agmatine supplements with protein-rich foods (and especially not a protein shake) because these often contain L-Arginine or Citrulline.
However, if you were to take Agmatine as a pre-workout, and waited at least 1 hour before using an amino acid supplement, it would be unlikely for these interactions to occur.
| Agmatine Sulfate | L-Arginine | L-Citrulline |
| Synthesized from L-Arginine | Synthesized from L-Citrulline | Essential amino acid |
| + Reduces sensations of pain | + Supports a healthy circulatory system | + Reduces fatigue |
| + Reduces feelings of stress | + Mildly improves blood flow | + Reduces muscle soreness |
| + Energizing effects | – Ineffective uptake into blood stream | + Boosts nitric oxide production |
How to Take Agmatine Sulfate
Agmatine is a white to off-white powder with a bitter taste and a sulfur-like smell. It is soluble in water and is best taken orally in a liquid beverage of your choice. Use a micro-scoop to measure the correct serving size. Alternatively, you can use the ‘toss and wash’ method.
Agmatine’s recommended serving size is between 600 – 1200 mg, taken once or twice daily. It is not recommended to exceed a daily serving size of 2400 mg (2.4 grams).
It is best taken in the morning, or around 15 – 30 minutes before exercising. It can be used as pre-workout or added to a pre-workout mix. It has good absorption and the effects are usually felt within 15 – 30 minutes.
If you’re taking Agmatine with other supplements, it is recommended to use a smaller serving size, as it may potentiate (increase) the effects of a number of other substances. This is especially true for Kratom and other relaxing or stress-relief supplements.
DO NOT TAKE AGMATINE ALONGSIDE ANY MEDICATION. It has not been studied fully in humans and may cause dangerous interactions.
Medical Disclaimer
Not intended to treat, diagnose, or cure any disease or ailment. Use with CAUTION.
References:
[1] Fluyau, D., & Revadigar, N. (2017). Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom. Frontiers in psychiatry, 8, 62.
[2] White, C.M. (2017). Pharmacologic and clinical assessment of kratom. Am J Health Syst Pharm. 2018 Mar 1;75(5):261-267. Review.
[3] US Food and Drug Administration. (2018). Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s scientific evidence on the presence of opioid compounds in kratom, underscoring its potential for abuse. Fga.gov [online] Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm595622.htm
[4] Singh, D., Müller, C.P., Vicknasingam, B.K. (2014). Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend, 1;139:132-7.
[5] Li, J., Li, X., Pei, G., Qin, B.Y. (1999). Effects of agmatine on tolerance to and substance dependence on morphine in mice. Zhongguo Yao Li Xue Bao.
[6] Agmatine sulfate is amazing for tolerance. (2017). Reddit.com [online]. Available at: https://www.reddit.com/r/kratom/comments/7lck4q/agmatine_sulfate_is_amazing_for_tolerance/
[7] Agmatine Sulfate. (2015). Ilovekratom.org [online]. Available at: http://www.ilovekratom.com/kratom-forum/kratom-discussion/2748-agmatine-sulfate
[8] Kamel, P. (2018). Creatine. Examine.com [online] Available at: https://examine.com/supplements/creatine/
[9] Bemben, M.G., Lamont, H.S. (2005). Creatine supplementation and exercise performance: recent findings. Sports Med, 35(2):107-25.
[10] Uzbay, T., Kose, A., Kayir, H., Ulusoy, G., Celik, T. (2010). Sex-related effects of agmatine on caffeine-induced locomotor activity in Swiss Webster mice. Eur J Pharmacol, 25;630(1-3):69-73.
[11] Is agmatine good with caffeine? (2016). Reddit.com [online] Available at: https://www.reddit.com/r/Nootropics/comments/595u8z/is_agmatine_good_with_caffeine/
[12] Yang, X.C., Reis, D.J. (1999). Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther. 288(2):544-9.
[13] Diler, A.S., Ziylan, Z.Y., Üzüm, G. (2013). N-methyl-D-aspartate Receptors Are Involved in Caffeine-Induced Facilitation on Memory Retention of Passive Avoidance Learning in Rats. Journal of Caffeine Research, 3:4, 169-174
[14] Kamel, P. (2018). Arginine. Examine.com [online] Available at: https://examine.com/supplements/arginine/
[15] Kamel, P. (2018). Citrulline. Examine.com [online] Available at: https://examine.com/supplements/citrulline/
[16] Kamel, P. (2018). Agmatine. Examine.com [online] Available at: https://examine.com/supplements/agmatine/
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