Gaba Supplements: Glorious, Gimmicky or Just Garbage?

7 minutes read
Image created by Ada McVean
Originally posted here: https://mcgill.ca/oss/article/health/gaba-supplements-glorious-gimmicky-or-just-garbage

Take-home message:
– gamma-Aminobutyric acid (GABA) is a major neurotransmitter that regulates much of our brain function. It was previously thought that ingested GABA could not cross the blood-brain barrier, but new research suggests that it may be able to.
– Drugs that mimic the action of GABA are numerous, work in a variety of ways, and can have effects ranging from treating epilepsy to causing it.
– GABA supplements have shown some promise in early, small-scale studies, but a lot more research is needed to know if they truly help.

Lately, it seems that GABA supplements are being hawked on the corner of every pharmacy aisle and health food shelf. Marketed to promote relaxation, mental focus and sleep, GABA is even being sold by David’s Tea in the form of GABA guava tea. I found it while trying to buy some matcha powder. I don’t even like guava, never mind guava with a side of inflated claims.

While promotions by influencers like Olivia Culpoand Sarah Couture are pretty standard for any trendy supplement, (regardless of efficacy) the attention GABA has been given by known quacks like Dr. Oz,Joseph Mercola orMike Adams has left me wondering about the science behind, and evidence for, these supplements.

Let’s start with the basics: what is GABA?

gamma-Aminobutyric acid (also written as γ-aminobutyric acid) is a neurotransmitter, specifically the major inhibitory one in all mammal’s central nervous systems (CNS). That means that it’s a chemical that binds to nerve cell receptors and hinders their ability to receive, create or send messages to other nerve cells (neurons).

Functionally, GABA is incredibly important. A lack of GABA leaves your central nervous system with too many neuronal signals and causes conditions like epilepsyseizures or mood disorders. Meanwhile, too much GABA means not enough brain activity and can lead to hypersomnia or daytime sleepiness.

You can learn more about GABA in this lovely video, and more about neurotransmitters in general in this one, although I’ve said all you’ll need to know for this article.

GABAergic drugs

As the chief inhibitory neurotransmitter in the CNS, GABA and its receptors have been major targets for drug development. Drugs that activate GABA receptors (called agonists) or increase the receptors’ sensitivity to GABA (positive allosteric modulators) work to reduce the neuronal signals in the user’s brain, similar to what happens when you sleep. Logically, they include many common sedatives like barbital or Quaaludes, tranquillizers like ValiumAtivanor Xanax and the most commonly used sedative, alcohol.

GABA reuptake inhibitors like Deramciclane have similar effects, as they help to keep GABA in the vicinity of the receptors for longer.

On the flip side, substances that inhibit the activity of GABA (called antagonists) increase brain activity. That only sounds like a good thing. The results are less Scarlett Johansson in Lucy, more uncontrollable seizures and death.

GABA antagonists, like gabazine or bicuculline are only useful when studying seizures or to counteract overdoses of sedatives and tranquillizers. Some GABA antagonists are particularly scary poisons, causing death by disrupting the CNS’s control of basic body functions like breathing.

The class of drugs we’re most interested in, however, are GABA analogues. These molecules are structurally similar to GABA, though they have different targets of action. GABA analogues include some big names you’ve probably heard of: Lyrica and gabapentin.

While both Lyrica and gabapentin are prescribed to stop seizures, treat neuropathic pain, and anxiety disorders, gabapentin is additionally used for the prevention of migraines.

Gabapentin has been a constant in my life for a few years now, as my mother was prescribed it for diabetic neuropathic pain just a few years after my partner was prescribed it for near constant migraines. I’ve personally seen GABA to be quite effective in its on-label uses, as the evidence shows it to be, but it was recently at the heart of one of the largest court settlements in US history.

The manufacturers of gabapentin were found to have been marketing it extensively for off-label uses like the treatment of bipolar disorder, restless leg syndrome, hot flashes and stopping smoking. While off-label prescribing is not uncommon, and usually fairly safe, there is no evidence that gabapentin is effective for the bipolar disorder it was being prescribed to treat or some of the other conditions for which it’s being prescribed.

Presently gabapentin is again making headlines as its use as a recreational drug skyrockets. Many opioid users are misusing gabapentin to extend opioid highs or bypass drugs that block opioids effects, but its status as a non-controlled substance makes it difficult for law enforcement to control its unsanctioned use.

GABA and the Blood-Brain Barrier

GABA drugs are certainly useful, but why do we need all these GABA-receptor-activating or GABA-like molecules in the first place? Why not just give patients GABA?

We have a highly selective membrane that keeps our blood and cerebrospinal fluid (or brain juice, if you will) separate: the blood-brain barrier (BBB). Some molecules, like water, pass through it easily, other things, like bacteria don’t. This membrane also contains special channels to diffuse important molecules one way or the other, like glucose.

It’s a really important border, as drugs that cannot cross into the brain, or do so poorly, have much less of an effect than ones that do. For example, morphine can’t cross the BBB very well, but it’s close relative heroin can! Upon entry to the brain, heroin is converted into morphine, which is why heroin is so much more potent than morphine.

A 1958 study was the first to look at GABA’s relationship with the blood-brain barrier, and it found a lack of one: GABA could not cross the barrier. Later studies in ‘58‘71, and ‘88 confirmed the barrier’s impermeability to GABA. The evidence seems all but clear until you throw a few more studies into the mix. Studies done in ‘80‘81‘82 and ‘02 found that GABA did cross the blood-brain barrier, just in minuscule amounts.

Why the disagreement? Well, a few things. Some studies used a molecule just like GABA in lieu of GABA, assuming the 1 extra OH group featured on 3-hydroxybutyric acid wouldn’t make a difference, but it may have. Since many studies don’t report the type of GABA used, it’s hard to compare results. Some studies administered their GABA by injecting it straight into animal’s body cavities, others by injecting it into veins.

Most importantly, the BBB permeability of GABA has never been studied in humans!

What we do know is that human’s BBB contains transporters for GABA, implying that GABA can enter/exit the brain through these channels. In mice it was found that GABA was removed from the brain 17 times faster than it entered.

This could explain the conflicting study results. It may not be that GABA cannot enter the brain, but just that it’s removed from it very rapidly.

GABA as a Supplement

Even if it cannot cross the BBB however, GABA could still be affecting your brain.

The enteric nervous system (ENS) is the network of neurons that control your gastrointestinal system. The ENS contains many GABA receptors, and GABA itself, and is connected to the brain through the vagal nerve. It’s been proposed that ingested GABA is able to affect the body even without crossing the BBB through its interactions with the ENS.

We don’t know at this point how GABA is affecting the brain, but we have good evidence that it is. Several studies have shown reductions in markers of stress in patients given dietary GABA.

On their own the success stories from the consumers who buy GABA supplements are meaningless but taken along with the research findings, they may just show that there is something to these supplements.

We’ll need a lot more research to know for sure if GABA supplements are helpful or not. That being said, they are expensive (like most supplements) and if you’re not anxious, experiencing insomnia or very stressed out they’re probably not worth it. There don’t appear to be many side effects or drug interactions, but until more research is done I’d tread carefully.

I did ask my partner, who took gabapentin (a GABA analogue) for years if he ever experienced any focusing of his mind or relaxation as the GABA supplements claim. He said a definitive no.

Want a cheaper option for relaxation? Tea. You can even try some GABA tea, a strain of green tea specially fermented to accumulate GABA. Maybe I’ll pick some up… just not that guava flavoured stuff.

How to Make the Healthiest Cup of Tea

Photo by Matteo Zamaria
Originally published here: https://mcgill.ca/oss/article/health-and-nutrition-quackery/how-make-healthiest-cup-tea

grew up with British grandparents who probably averaged 5-7 cups of tea a day- a routine I picked up sometime around the age of 10. I never considered though that tea could be good for me! We’ve written quite extensively on tea and it’s many proposed benefits, but despite all the pseudoscience about tea curing cancer or keeping you young, it is worth it to note the compounds that are found in teas, that are truly helpful to humans.

L-theanine is an amino acid analogue to glutamate, the most abundant excitatory neurotransmitter in the brain, and is also responsible for the umami taste found in green tea. Some studies have found that it favourably affects stress responsesmemory and attention span, with special research attention being payed to the positive effects on cognition that substances containing both theanine and caffeine have.  The catechins can be found in tea and are antioxidants, and have been found to help lower blood pressure (especially when systolic pressure are over 130 mm Hg), and may help regulate blood flow in humans. A recent study found that catechins may favourably effect cholesterol as well.

As with everything however, it doesn’t matter how helpful a compound is if there isn’t a relevant dose of it present. A 2011 study looked at the L-theanine in teas, and found black teas to contain the most, ~24 mg/200 ml, and green tea the least, ~8 mg/200 ml. This study also found that adding milk to tea caused a noticeably decrease in theanine content, and that in general, the longer you brewed your tea, the more theanine it contained. Most supplement bottles seem to recommend taking 200-400 mg per day, or the equivalent of about 8-16 cups of black tea, or 25-50 cups of green tea. That’s a lot of tea, even for me

If you do want to get the most out of your tea however, you’re in luck! A lot of research has looked at the most effective way to extracting theanine and catechins from tea leaves, but the results are… interesting. A 2011 study found that steeping quite a fine grind of green tea leaves in 80 °C water for 30 minutes, using a 20:1 ml/g water to tea ratio yielded the best results. For reference, most cups of tea are made with about 200 ml of water to 2 g of tea- a 100:1 ml/g ratio. I just don’t know that I want to drink a cup of tea that strong, even for nutritional benefits.

A 2012 study suggested a slightly different method for tea compounds- microwaving. By placing a tea bag in boiling water for 30 seconds, then microwaving it for 1 minute, the authors were able to improve the extraction of catechins by 18%, though the theanine extraction was not affected. If you’re anything like me however, your heart skipped a beat when I mentioned microwaving tea. Let me assure you however, having tried the described brewing method, it’s not so bad. Not as good an old-fashioned steeping, but not terrible. Keep in mind though, that even in this improved method, only 61 mg of catechins per g of tea, and 10 mg of theanine per g of tea are being extracted. In cup of tea made with 2 g of leaves, that’s ~ 122 mg of catechins and 20 mg of theanine per cup. So if you’re hoping to use tea instead of supplements, I’d still recommend black varieties, and maybe sticking close to a bathroom (my Nana always said, tea goes right through you).

The key to cleaning your teapot is chemistry

Originally published here: https://mcgill.ca/oss/article/did-you-know-general-science/key-cleaning-your-teapot-chemistry

Do you ever try to wash a mug only to be confronted by tea stains that just won’t budge? A little bit of chemistry may be just what you need to get your mugs back to white.

Brewed tea, green or black, contains many compounds, including many polyphenols. These are compounds found naturally in tea leaves that have antioxidant properties and contribute to the taste of tea. However, they are also responsible for the stains left in your mugs and teapots.

Polyphenols are a large group of complex molecules that are structurally similar in that they all contain simpler components known as phenols. Tannins are a class of polyphenols that provide tea with its characteristic hue, and are responsible for those annoying stains. Being largely impervious to scrubbing, how can these stains be removed?

A little bit of chemistry.

Black tea has a pH of 4.9, meaning that it is slightly acidic. While tannins encompass a wide variety of compounds, they all tend to be slightly acidic. As such, to remove them from the sides of your mug, you need to neutralize them with a base. the most readily available of which tends to be baking soda.

Just make a paste of baking soda and water, rub it onto your stained crockery, leave it for 20 minutes or so, and then wipe it off with a sponge. It certainly worked wonders on my now much-cleaner teapot.