GABA - An Effective Sleep Aid W/ GH Boosting Effects that Works Within 30 Minutes - Only 100 mg Pre-Bed Will Suffice

GABA - An Effective Sleep Aid W/ GH Boosting Effects that Works Within 30 Minutes - Only 100 mg Pre-Bed Will Suffice

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Spinach and beans, two good sources of dietary GABA - 42 µg/g in spinach, 25 µg/g in beans (Oh. 2003)

You may remember my previous article about GABA and the accompanying discussion I had with my friend Carl Lanore on Super Human Radio in 2013 (learn more); and if you do, you will probably also remember that I have mentioned that some people have a paradoxical reaction to GABA.

Instead of getting tired, they get wired. Whether that's related to the likewise previously discussed effects on glucose management and a potential stress response to hypo-glycemia is not clear and I have to admit: The latest GABA study does not provide an answer to this question either.

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What Yamatsu's study does provide, however, is very good evidence that γ-aminobutyric acid (GABA) acts as a potent sleep aid in the average Japanese... about as average as the ten subjects (average age: 37.7±11.5, age range: 24-57, 6 male subjects and 4 female subjects), who were suspected to have small sleep disorders but were not patients, that participated in this study.

Yamatsu et al. used a randomized, single-blind, placebo-controlled, crossover-design, according to which the ten subjects were randomly divided into two groups of five people each (group 1 and group 2). The main study consisted of two intake periods (1 week each) and a wash out period (1 week) between the intake periods. During the first intake period, subjects in groups 1 and 2 took GABA and the placebo, respectively, 30 min before going to bed everyday for a week. During the second intake period, the treatments were exchanged between groups (i.e. subjects in group 1 and group 2 took the placebo and GABA, respectively).

GABA content of selected uncooked foods (Yamatsu. 2016).

"For two consecutive nights three days prior to each intake period, the subjects went to bed wearing the EEG instrument for adaptation. On the night prior to each intake period, EEG recordings were obtained while the subject was sleeping to serve as the baseline data. EEGs were also collected on the last night of the intake periods. On days that EEGs were recorded, alcohol and drugs, such as cold medicine and hypnotics, were prohibited. In addition, food and drinks, such as coffee, tea, and other items that might affect natural sleep, were also prohibited 2 h before going to bed. Subjects were requested to maintain constant lifestyle patterns regarding their eating habits, exercise, daily work, and so on throughout the study" (Yamatsu. 2016). 

On the day following the EEG measurement, subjects evaluated their sleep with respect to ease of falling asleep, feelings upon awakening, and satisfaction with sleep by using visual analog scores (VAS). Subjects gave high scores if they felt positive effects from the test samples. In addition to VAS,  Pittsburgh Sleep Quality Index (PSQI | Burysee. 1989) was used to evaluate the sleep quality of each subject.

Serum GABA levels over time (Yamatsu. 2016).

How do we know 30 minutes before bed if optimal? In a follow up study, the researchers  were given 100 mL of water with 200 mg of GABA (more for the dose-response (2) vs. the sleep study (1) study), in order to determine the exact plasma GABA kinetics over 60 minutes. What they found is the data in the figure on the left that clearly indicates that the GABA levels and thus probably its effects peak after 30 minutes. Whether this means that your sleep will be the deepest or most recuperative with this timing cannot be guaranteed, though.

And this evaluation yielded quite interesting results: Oral administration of 100 mg of GABA significantly shortened sleep latency by 5.0 min (p=0.020, Fig. 1A, left). The mean value of sleep latency of subjects before GABA administration was approximately 10 min, and their sleep latency after GABA administration was reduced by half.

Figure 1: EEG data and subjective data from the VAS and PSQI test (Yamatsu. 2016). 

The scientists also point out that although there was no significant difference, deep non-REM sleep latency was also shortened in GABA group by 4.1 min (Fig. 1B) and elaborate:

"These results indicate that GABA may help people fall asleep quickly and easily. In other words, GABA exhibited its effect during the early stage of sleep. Besides shortening sleep latency, GABA significantly increased total non-REM sleep time by 2.2% (p=0.040, Fig. 1E). This is favorable because non-REM sleep is a deeper sleep and is thought to rest both the brain and the body. In particular, the time from falling asleep to the first REM sleep, which was in the early stage of sleep and consisted of light and deep non-REM sleep, was longer in the GABA group compared to the placebo (data not shown). This also indicated that GABA was effective, especially during the early stage of sleep" (Yamatsu. 2016). 

The results of sleep evaluation by VAS questionnaires and PSQI are shown in Fig. 1 on the right hand side: Every item of VAS and PSQI was improved in GABA group. For the scientists, that's sufficient evidence that "subjects in the present study felt certain effects after use of GABA".

Now that's cool, but what is even more important than the subjects felt any effect is that their "feelings upon awakening were significantly improved" (p=0.025, Fig. 1A, right | Yamatsu. 2016). This is important, because some drugs used for sleep treatments are so strong that people will feel drowsy and tired on the next morning, in spite of sleeping more than usual. Compared to these drugs, i.e. benzos and co, GABA is thus not just safer and over-the-counter available, it will also leave you less winded on the next AM. Unfortunately, it is questionable, whether GABA strong enough for people with severe sleep disorders - personally, I doubt that.

GABA Supplementation Shown to Improve Glucose Management - Even in Healthy Subjects, There's a Significant Reduction in Glycated Albumin Levels After Only 7 Days on 3x2g GABA per Day | learn more

Bottom line: In view of the previously discussed beneficial effects on growth hormone and glucose management, GABA is an interesting supplement for anyone. Its ability to shorten sleep latency and increase the total non-rapid eye movement (non-REM) sleep time, however makes it even more attractive for people with mild sleep disturbances and people who love to mess with their biorhythm to fine-tune it even further.

From the slightly sarcastic tone in the last sentence of the previous paragraph, you may already have concluded that I am not going to suggest everyone should supplement GABA: no long-term data, no real need... so you better only consider it, if you have sleep issues | Comment!

References:

• Buysse, Daniel J., et al. "The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research." Psychiatry research 28.2 (1989): 193-213.
• Oh, Suk-Heung, Yeon-Jong Moon, and Chan-Ho Oh. "γ-Aminobutyric acid (GABA) content of selected uncooked foods." Preventive Nutrition and Food Science 8.1 (2003): 75-78.
• Yamatsu, Atsushi, et al. "Effect of oral γ-aminobutyric acid (GABA) administration on sleep and its absorption in humans." Food Science and Biotechnology 25.2 (2016): 547-551.

GABA Supplementation Improves Glucose Management - Even in Healthy Subjects | Significant Reduction in Glycated Albumin Levels After Only 7 Days on 3x2g GABA per Day

GABA Supplementation Improves Glucose Management - Even in Healthy Subjects | Significant Reduction in Glycated Albumin Levels After Only 7 Days on 3x2g GABA per Day

anti-diabetes beta cells blood glucose diabetes gaba gamma aminobutyric acid glucagon glucose management health insulin lose fat

No acute changes in blood glucose, but extreme changes in insulin levels. How can this trigger a reduction in glycated albumin - How's that possible? 

You've read about gamma aminobutyric acid (GABA) at the SuppVersity before. While most people think of it mainly as a calming agent, though, SuppVersity readers know that it has the remarkable ability to heal the insulin producing β-cell in rodents by stimulating their replication, protecting them against apoptosis, and attenuating insulitis (Soltani. 2011; Tian. 2013; Prud'homme. 2014; Purwana. 2014). And while these favorable effects were first observed in mice, researchers are quite sure that they are valid in humans, too- that's also because said effects have been confirmed only recently by Tian et al. (2014) and Purwana et al. (2014) in vitro as well as in xenotransplanted human islets.

Learn more about the effects of GABA & co at the SuppVersity

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If you know that, the observations researchers from the Fudan University in Shanghai report in their latest study probably won't come as a surprise. In their investigation into the  pharmacokinetics and pharmacodynamics of GABA in healthy volunteers, the researchers found that the chronic provision of 2g of GABA three times per day triggers a highly significant decrease in glycated albumin (GA) levels, the intermediate measure of blood glucose control (in-between acute blood glucose measurements and HbA1c | Roohk. 2008), within only 7 days.

Figure 1: Acute glucose (top) and insulin (bottom) response after single and repeated administration of 2g of GABA (left). Chronic effects of repeated dose-administration of GABA on glycated albumin (right | Li. 2015).

If you scrutinize the data in Figure 1, though, there are a few questions we still need to find answers to. Obviously, the acute administration of GABA (Figure 1, left) lead to significant increases in insulin - both, under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p < 0.01).

Glucose, insulin and glucagon: Let's briefly recap how the three are related. To lower your glucose levels, your body produces insulin which will then tell your cells suck the glucose from the bloodstream. If the glucose levels are getting lower and lower, your body produces glucagon which will then trigger a cascade of events to increase your blood glucose levels. This can be done by mobilizing stored glycogen (mostly from the liver) or producing new glucose via gluconeogensis - a process that relies heavily on amino acids, first and foremost alanine and glutamine.

Usually, this 1.4-fold or 1.6-fold increase in insulin should trigger a significant (at least transient) decrease in blood glucose. Since the latter wasn't the case in either the fasted or the fed tests the scientists conducted on the twelve subjects, who participated in the open-labeled, three-period trial, it appears more than counter-intuitive that the chronic administration of GABA which does not accumulate in the body and was found to be almost completely absorbed in 60 minutes and to have a half-life of 5h still lead to an GA decrease of approximately 11-12%.

Now this obviously confirms that GABA, due to its ability to increase islet hormonal secretion, has potential therapeutic benefits for diabetes, what the study does not tell us, though, is whether the lack of immediate effects on blood glucose levels can, as the scientists suspect, "in part be attributed to GABA-induced counter regulatory mechanisms, especially elevated glucagon" (Li. 2015) which rose so that the insulin-to-glucagon ratio remained unchanged. Yet while the latter could explain why the subjects did not become hypoglycemic in the face of increased insulin levels, the lack of certainty with respect to the underlying mechanisms makes the study results difficult to interpret.

As a loyal SuppVersity reader you will know that I talked about the potential need to re-balance glucose levels and its paradoxically agitating effects in a 2013 episode of SHR, already.

So what's the verdict, then? Whether and for whom GABA can be useful tool to improve his or her blood glucose management is virtually impossible to tell based on the study at hand. In spite of the fact that the scientists observed only minor adverse events such as transient dizziness and a sore throat, a further reduction of glycated albumin levels is not necessary an advantage that's worth having elevated insulin and glucagon levels. The latter would after all promote the use of proteins or rather amino acids as substrate for gluconeogenesis, the process of which the scientists believe that it is responsible for the non-existent instantaneous glucose response in the study at hand, while the former, i.e. the increase in insulin levels, is well-known for its negative effects on fatty acid oxidation.

Overall, "the verdict" is thus that we need additional research in both, healthy and diabetic individuals to be able to tell for whom the benefits of chronic high(er) dose (3x2g per day) GABA supplementation outweigh potential side effects. If you asked me for an educated guess, though, I would say (pre-)diabetics benefit while the average individual sees either no relevant benefits or detrimental effects due to the repeated need to re-stabilize the blood sugar levels... a phenomenon of which I have by the way previously said and written that it may explain the paradoxically agitating effects the ingestion of GABA has on some individuals - most likely those with already low(ish) blood glucose levels | Comment on Facebook!

References:

• Li, Junfeng, et al. "Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics." Frontiers in Pharmacology 6 (2015): 260.
• Prud’homme, Gérald J., et al. "GABA protects human islet cells against the deleterious effects of immunosuppressive drugs and exerts immunoinhibitory effects alone." Transplantation 96.7 (2013): 616-623.
• Prud’homme, Gérald J., et al. "GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity." Biochemical and biophysical research communications 452.3 (2014): 649-654.
• Purwana, Indri, et al. "GABA promotes human β-cell proliferation and modulates glucose homeostasis." Diabetes 63.12 (2014): 4197-4205.
• Roohk, H. Vernon, and Asad R. Zaidi. "A review of glycated albumin as an intermediate glycation index for controlling diabetes." Journal of diabetes science and technology 2.6 (2008): 1114-1121.
• Soltani, Nepton, et al. "GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes." Proceedings of the National Academy of Sciences 108.28 (2011): 11692-11697.
• Tian, Jide, et al. "γ-Aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model." The Journal of Immunology 173.8 (2004): 5298-5304.
• Tian, Jide, et al. "Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis." Autoimmunity 44.6 (2011): 465-470.
• Tian, Jide, et al. "γ-Aminobutyric acid regulates both the survival and replication of human β-cells." diabetes 62.11 (2013): 3760-3765.
• Tian, Jide, et al. "Combined Therapy With GABA and Proinsulin/Alum Acts Synergistically to Restore Long-term Normoglycemia by Modulating T-Cell Autoimmunity and Promoting β-Cell Replication in Newly Diabetic NOD Mice." Diabetes 63.9 (2014): 3128-3134.