ANXIETY? THESE EVIDENCE-BACKED SUPPLEMENTS CAN HELP!



The use of psychiatric meds has increased dramatically over the past 15-20 years, which corresponds with significant increases in the number of Americans diagnosed with a psychiatric disorder. Approximately 40 million U.S. adults suffer from an anxiety disorder and another 17 million from clinical depression. It’s also estimated that another 8-14 million suffer from PTSD. [1]


When facing a mental health challenge many turn to psychiatric meds or counseling for help. And why not? American consumers are saturated with marketing from the pharmaceutical industry (FYI the U.S. is 1 of only 2 countries in the world that allows pharmaceutical companies to market directly to consumers). Most Americans don’t know that there are safe, effective, natural and clinically-backed alternatives to psychiatric meds. Compounding the issue, many PROVIDERS are undereducated on these options as well. [2]


WHAT ARE NEUROTRANSMITTERS?

To gain a basic understanding of some of the natural solutions to psychiatric and mood-related conditions we first need a basic understanding of nerve cells (aka neurons) and neurotransmitters. This is an especially critical areas as an estimated 86% of Americans have suboptimal neurotransmitter levels. [3]


A nerve cell/neuron is a cell that receives, processes and transmits cellular information through chemical and electrical signals. Neurotransmitters play a central role in this transmission of data. Perhaps a couple images will help to illuminate how this works…




As you can see, a nerve impulse travels through the axon to the axon terminals, where vesicles containing neurotransmitters are stored. The nerve impulse stimulates the vesicles to release the neurotransmitters, after which they “jump” across the synaptic cleft to the receptor cite of the other cell (this receptor cell may be a nerve cell, muscle cell or gland cell). Because of this activity, neurotransmitters are sometimes referred to as the body’s chemical messengers.


The study of neurotransmitters is relatively new, and officially began in 1914 when the first neurotransmitter, acetylcholine, was discovered. Since that time the list of neurotransmitters (and chemical agents with neurotransmitter-like capabilities in the body) has continued to expand. Today there are around 100 neurotransmitters (or neurotransmitter-like chemical agents) that have been identified.


Neurotransmitters can be categorized several different ways- by molecule size (small or large), by chemical type (amino acid-derived, lipid-derived, vitamin-derived) or by their effect on the body (inhibitory vs excitatory). For our discussion today we will use the latter. [4-5]


While there are dozens of chemical agents possessing neurotransmitter effects, there are 7 or 8 which have received the majority of the scientific attention, as it’s thought that they perform the vast majority of the NT functioning in the body. This list includes acetylcholine as well as excitatory NTs like glutamate, dopamine, adrenaline (i.e. epinephrine) and noradrenaline (i.e. norepinephrine), inhibitory NTs like serotonin and GABA, and other NTs such as oxytocin. [6-7]


When discussing neurotransmitters and their effects on the body I think it’s also important to touch on the related nutrients, chemicals and nutritional supplements that help to support the body’s production of these vital and often powerful chemical messengers. I’ll try to do that in the information that follows.


ANTIDEPRESSANTS, ANTIPSYCHOTICS

AND MOOD STABILIZERS (OH MY!)…

Many people start researching neurotransmitters in an attempt to improve mood and psychological health (including conditions like depression and anxiety), and often with a goal to do so without using pharmaceuticals. Indeed, conventional medicine’s first line of treatment for these conditions often includes psychiatric medications such as…



Antidepressants, including…

o TCAs like amitriptyline

o SSRIs like Paxil, Zoloft and Prozac

o SNRIs like Cymbalta and Effexor and

o Atypical antidepressants like Wellbutrin (an NDRI-class drug)


Antipsychotics (aka major tranquilizers/sedatives), including

o Benzamides

o Benzisoxazoles like risperidone

o Butyrophenones like haloperidol

o Diphenylbutylpiperidines like pimozide

o Phenothiazines like chlorpromazine

o Thioxanthenes like clopenthixol and

o Tricyclics like clozapine, olanzapine and quetiapine

Mood stabilizers, including…

o Anti-seizure drugs like valproic acid/Depakote and

o Lithium carbonate



MENTAL DISORDERS ARE BIG BUSINESS

As you can see from the image below, mental health disorders are not only widespread in America, they’re also big business. While abortion, cardiovascular disease and cancer kill more than 900,000, 750,000 and 600,000 Americans a year, respectively, it’s mood issues and mental disorders like anxiety and depression where Americans spend the most money. And where massive profit potential exists, the pharmaceutical and medical device industries are strongly present. But what’s wrong with the vast majority of psychiatric medication? Simple. These medications generally “work” not by supplying an essential nutrient or by supporting a fledgling natural process in the body, but rather by inhibiting, suppressing or working against important metabolic and neurological processes in the body. [8-9]



NATURAL SOLUTIONS: BALANCING

INHIBITORY & EXCITATORY NEUROTRANSMITTERS

The natural solutions for mood disorders center around nutrition and lifestyle and their effect on neurotransmitter (NT) functioning. As stated above, neurotransmitters can generally be divided into 2 camps- inhibitory and excitatory.


INHIBITORY NEUROTRANSMITTERS

The chief inhibitory NTs are GABA and serotonin. Incredibly, 70-90% of serotonin is produced in the gut! As you might guess, inhibitory NTs have a calming effect on mood. While serotonin may get more press, GABA is actually the major inhibitory neurotransmitter in the brain and occurs in some 30-40% of all synapses there. [10]


"70% of your serotonin is made in your gut. What's going on in your gut is going to affect your mood- anxiety, depression and focus." ~Dr. Frank Lipman MD


Other nutrients and chemicals that have inhibitory neurotransmitter capabilities, although often milder than GABA and serotonin, include glycine (which, in supplement form, is often used as a sleep aid, intestinal aid and collagen booster) and taurine (which, in supplement form, has been shown to be beneficial for liver health, eyesight and cardiovascular health, specifically hypertension). [11-12]


EXCITATORY NEUROTRANSMITTERS

The chief excitatory NTs are glutamate and dopamine. Roughly 50% of dopamine is produced… in the GUT! Other major excitatory NTs include epinephrine and norepinephrine (aka adrenalin and noradrenalin).


The gut is so central to brain and neurotransmitter functioning that the gut is often referred to as the “enteric nervous system” or more commonly “the second brain.” The link between the brain and the gut has been highlighted with terms like “gut-brain axis” and the “food-mood connection.” Indeed, the vagus nerve is a 2-way information superhighway that connects 200-600 million nerve cells that run from the intestines to the brain. [13]


Other chemicals that have milder excitatory NT effects include histamine (yes, the one associated with allergies and itching) and PEA (aka phenyl-ethylamine). It’s important to note that dopamine can be both an excitatory AND inhibitory NT, depending on the type of receptor it binds to (confusing, right?!). [14-15]



NEUROTRANSMITTER LAB TESTING

Oftentimes, an anxiety disorder will involve either low levels of inhibitory NTs, high levels of excitatory NTs, or a combination of both.


Conversely, many depressive disorders involve high levels of inhibitory NTs, low levels of excitatory NTs, or a combo of both.


I encourage people to first get tested if possible. There are several methods for assessing neurotransmitter levels, including saliva, blood serum, cerebrospinal fluid and urine tests. According to most experts, urine testing is the most practical and shows the best clinical correlations. NT levels do fluctuate considerably over the course of a day, so while single point urine collection can give you an idea of your levels over the last 2–3 hours, it’s best to collect multiple measurements (urine samples) over several hours.


Also note that there are at least four foods that are known to produce false positive results. These foods can send urinary neurotransmitter levels sky high for hours after you eat them. As such, it’s essential to avoid consumption of the following items for the 48 hours leading up to your collection date…


· Bananas and plantains

· Nuts (especially walnuts) and nut butters

· Pineapples and

· Avocados [16]


While NT testing is in its infancy (and the accuracy of urine NT tests has been called into question by some), there are several NT tests available, like those offered by ZRT and Doctor’s Data. These labs can be purchased through online retailers like Life Extension, True Health Labs and Amazon. The Organic Acids Test also shows 7 NT markers.


7 SUPPLEMENTS FOR ANXIETY: 5-HTP, GABA,

MAGNESIUM, CBD, THEANINE, GLYCINE & TAURINE

For those with low inhibitory NTs and who are dealing with anxiety, I generally suggest they start by considering 5-HTP or GABA supplements, depending on the details of their lab results. If lab testing hasn’t been done but assessment results and symptoms strongly suggest low inhibitory NTs, I usually suggest starting with 5-HTP and then moving on to GABA if needed.


5-HTP: THE SEROTONIN-BOOSTING SUPPLEMENT

5-HTP is a form of the amino acid tryptophan (5-hydroxytryptophan). Tryptophan is a serotonin precursor, which itself is a melatonin precursor…



Several studies have demonstrated 5-HTP’s positive effects on anxiety. A 2008 review of the data found that tryptophan has protective effects against Panic Disorder. Interestingly, several studies have indicated that tryptophan may be effective against depression as well, although a 2012 study in the journal Neuropsychiatric Disease and Treatment cautioned against this, as supplementing with 5-HTP alone can actually exacerbate depression symptoms, in part due to its effects on serotonin, and also due to depletion of excitatory neurotransmitters. For adults dealing with anxiety I generally recommend a 50-100mg dose of 5-HTP first thing in the morning and then a 100-200mg dose in the evening. [17-21]


GABA: THE MAJOR INHIBITORY NEUROTRANSMITTER

After 5-HTP, the next neurotransmitter-supporting supplement for anxiety we’re looking at is GABA. GABA (or more formally, gamma aminobutyric acid) is an amino acid-like compound created from glutamic acid (a non-essential amino acid) and vitamin B6. GABA is THE major inhibitory neurotransmitter of the brain, where it occurs in some 30-40% of all synapses there.


It shouldn’t come as a surprise that GABA is a popular supplement here, as several pharmaceutical drugs also target the GABA system in at attempt treat anxiety disorders. A 2006 study published in the journal Biofactors found that oral supplementation of GABA safely and effectively worked to induce relaxation and diminish anxiety, with effects seen within 1 hour of administration. That said, there is some conflicting scientific data on whether GABA is able to cross the blood brain barrier (BBB) with oral supplementation. [22-25]


For adults dealing with anxiety I generally recommend a 750-1500mg dose of GABA taken at night, usually after dinner or a couple hours before bedtime.


MAGNESIUM: THE SOFT TISSUE RELAXER

With anxiety, magnesium is another supplement I commonly recommend, as 50-75% of the U.S. adult population is deficient in this essential major mineral. Among its many roles in the body, magnesium causes the soft tissue to relax, which often helps with anxiety symptoms. For adults dealing with anxiety I’ll often suggest around 200mg of magnesium in the morning and another 300-500mg in the evening before bed. [26-27]



In addition to 5-HTP, GABA and magnesium, several other supplements are regularly used to combat anxiety, including glycine and taurine (which I already mentioned) as well as CBD (cannabidiol) and L-theanine.


CBD: SUPPORTING THE ENDOCANNABINOID SYSTEM

CBD, extracted from marijuana, has been shown to be a safe and effective therapeutic agent against anxiety disorders, in part through its positive effects on the endocannabinoid system (ECS). The ECS has been described as an ancient lipid signaling network which modulates neuronal functions and inflammatory processes, and which is also involved in the etiology of certain lifestyle-driven diseases. The ECS is able to downregulate stress-related signals that lead to chronic inflammation and certain types of pain (note that the ECS exists and is active in your body even if you don't use cannabis). [28].


Dozens of studies, most published over the last 10 years (2011-2021) have shown CBD as a safe and effective agent for the treatment of several anxiety disorders, including generalized anxiety disorder, panic disorder, social anxiety disorder, OCD and PTSD. With CBD, single doses generally range from 15-200mg, and are often taken 1-3 times a day. Dosage amounts up to 1500mg/day have been used with no adverse effects. [29-33]



L-THEANINE: THE SEROTONIN & GABA BOOSTER

L-theanine is an amino acid analogue of certain protein-building amino acids and is found naturally in green tea, black tea and some mushrooms. L-theanine has been shown to elevate levels of GABA and serotonin and several studies have shown that doses of 200-400mg/day (and up to 1500mg/day) are safe and effective for treating anxiety and other related mood conditions. [34-37]


“I take L-theanine, which is a natural supplement to help with stress and anxiety.”

~Taylor Swift, 10-Time Grammy Award Winning Artist


GLYCINE: THE SIMPLE AMINO ACID WITH ANTI-ANXIETY EFFECTS

Glycine is a conditionally-essential amino acid with a scientific track record for helping with an impressive variety of conditions, including digestive diseases, sleeping issues, joint pain, skin issues and mood conditions (including anxiety and even schizophrenia). [38-42]


Since the 1970s glycine has been considered an important inhibitory neurotransmitter, and studies have shown that there are many similarities between glycine and GABA. It shouldn’t come as a surprise, then, that still other studies have shown glycine supplementation to have anti-anxiety effects. [43-45]


Dosage-wise I generally recommend adults battling anxiety start with 2-3g (about ½ tsp of powder) in the morning and 4.5-9g (1-2 tsp) at night.


TAURINE: THE VERSATILE AMINO ACID THAT ALSO HELPS WITH ANXIETY

Taurine is a non-protein-building sulfur-containing amino acid that’s incredibly prevalent in the body (some research suggests it’s the most abundant amino acid in the body!). The scientific literature is full of data highlighting the benefits of taurine supplementation for a host of physical conditions, from cardiovascular diseases to neurological conditions to eye/vision health to liver & gallbladder functioning. [46-57]


Taurine also has inhibitory neurotransmitter effects and has been shown to be a safe and effective tool for treating certain types of anxiety. Taurine is a structural analog of the inhibitory NT GABA and activates both GABA and glycine receptors. [58-60]


Dosage-wise I suggest those battling anxiety to start with 1-3g of taurine, 1-2 times a day. While dosages over 7-8g/day are not regularly reported in the scientific data, anecdotal reports of using up to 14g with good effects have been reported.



ANXIETY? CAREFUL WITH CAFFEINE & SUPPLEMENTS THAT BOOST EXCITATORY NTs

For those battling anxiety I also suggest they consider eliminating caffeine, or at least reduce their intake to no more than 200mg a day. Supplements like glutamine and tyrosine can cause an increase in excitatory neurotransmitters like glutamate and dopamine, and for those battling anxiety this may prove problematic.


SOURCES

1 https://adaa.org/understanding-anxiety/facts-statistics

2 www.goodrx.com/healthcare-access/patient-advocacy/prescription-drug-advertising-regulation-united-states (U.S. and New Zealand only 2 countries that allow DTC advertising for pharma drugs)

3 www.zrtlab.com/test-specialties/neurotransmitters/ (86% of Americans with suboptimal NT levels)

4 www.animalresearch.info/en/medical-advances/nobel-prizes/the-discovery-of-neurotransmitters/ (1914; acetylcholine was discovered)

5 www.ncbi.nlm.nih.gov/books/NBK10795/ (2001; 100 neurotransmitters identified)

6 www.mvorganizing.org/what-are-the-7-major-neurotransmitters/

7 https://askthescientists.com/neurotransmitters/ (the 7 major neurotransmitters)

8 https://abort73.com/

9 www.cdc.gov/nchs/fastats/leading-causes-of-death.htm

10 www.frontiersin.org/articles/10.3389/fnint.2018.00033/full (90% of serotonin produced in the gut)

11 www.ncbi.nlm.nih.gov/pmc/articles/PMC1760744/ (2006; history of glycine and gaba as neurotransmitter)

12 www.ncbi.nlm.nih.gov/pmc/articles/PMC2994408/ (2010; taurine as a neurotransmitter)

13 https://pubmed.ncbi.nlm.nih.gov/24997029/ (2014 study on Vagus nerve and enteric nervous system)

14 https://pubmed.ncbi.nlm.nih.gov/21618891/ (2010; histamine as NT)

15 www.ncbi.nlm.nih.gov/pmc/articles/PMC3904499/ (PEA as a neurotransmitter)

16 www.zrtlab.com/blog/archive/neurotransmitters-food-avoid/

17 www.ncbi.nlm.nih.gov/pmc/articles/PMC3195213/ (2008; review of data on tryptophan and supplements [like 5-HTP] found tryptophan has protective effects against Panic Disorder; some conflicting data exists)

18 https://escholarship.org/uc/item/58h866d5 (2006; review on 5-HTP and depression concluded that 5-HTP supplementation deserves to be considered as possible significant addition to anti depression protocols)

19 www.ncbi.nlm.nih.gov/pubmed/11869656 (2002; a review of available data found only 2 high quality studies on 5-htp’s effects on depression; findings were that 5-HTP did alleviate depression better than placebo)

20 www.ncbi.nlm.nih.gov/pubmed/9727088 (1998; 5-htp crosses blood-brain barrier & increases serotonin in CNS; supplementing w/ 5-htp shown to be effective in treating depression, insomnia, fibro, binge eating & chronic headaches)

21 www.ncbi.nlm.nih.gov/pmc/articles/PMC3415362/ (2012; 5-htp can boost serotonin, an inhibitory neurotransmitter; supplementing w/ 5-HTP alone can actually exacerbate depression symptoms, in part due to its effects on serotonin & also due to depletion of excitatory NTs; treatment for mood disorders is highly individualized)

22 https://pubmed.ncbi.nlm.nih.gov/12662130/ (2003; several pharma drugs target the GABA system in an attempt to treat anxiety disorders)

23 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303399/ (2015; targeting GABA system in treating anxiety disorders)

24 https://pubmed.ncbi.nlm.nih.gov/16971751/ (2006; 2 small studies; "GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety")

25 www.ncbi.nlm.nih.gov/pmc/articles/PMC4594160/ (2015; conflicting data on whether GABA crosses the blood brain barrier)

26 www.sciencedaily.com/releases/2018/02/180226122548.htm (50% of Americans magnesium deficient)

27 www.ancient-minerals.com/magnesium-deficiency/ (75% of Americans magnesium deficient)

28 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820295/ (2013 study on ECS)

29 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/ (2015; preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, OCD and PTSD when administered acutely")

30 https://pubmed.ncbi.nlm.nih.gov/31866386/ (2019; review of 8 studies using dosages of 6-400mg/day found that "CBD has a promising role as alternative therapy in the management of anxiety disorders")

31 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/ (2019; "preclinical & clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety and schizophrenia")

32 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092763/ (2020; review of 25 studies found that "there was evidence to support single dose positive effect on social anxiety disorder" using CBD)

33 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917759/ (2021 review of the data found that “given CBD’s safety profile, these studies support the continued evaluation of CBD as a promising new agent in the treatment of anxiety and mood disorders”)

34 https://pubmed.ncbi.nlm.nih.gov/21208586/ (2011; 400mg/day of l-theanine can ameliorate anxiety symptoms in schizophrenia)

35 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836118/ (2019; "our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments")

36 https://pubmed.ncbi.nlm.nih.gov/31412272/ (2019; “theanine administered at daily doses ranging from 200 to 400 mg for up to 8 weeks are safe and induce anxiolytic (anti-anxiety) and anti-stress effects in acute and chronic conditions”)

37 https://pubmed.ncbi.nlm.nih.gov/31758301/ (2020; “200-400 mg/day of l-theanine may assist in the reduction of stress and anxiety in people exposed to stressful conditions”)

38 www.ncbi.nlm.nih.gov/pmc/articles/PMC6153947/ (2018; average 150lb person has 10g/day glycine deficiency, which can contribute to osteoarthritis; 10g glycine/day superior to 10g collagen hydrolysate for collagen synthesis in the body)

39 www.ncbi.nlm.nih.gov/pmc/articles/PMC5622680/#B70-nutrients-09-00920 (2017; evidence enough to support a hypothesis that glycine protects against colitis & IBD)

40 www.ncbi.nlm.nih.gov/pmc/articles/PMC3328957/ (2012; 3g/night glycine improved sleep quality)

41 www.ncbi.nlm.nih.gov/pmc/articles/PMC2713375/ (2009; positive effects of up to 0.8g/kg/day glycine for 5 days [~70g/day for 200lb man] for schizophrenia)

42 www.ncbi.nlm.nih.gov/pubmed/15205876 (2004; positive effects for schizophrenics with doses of ~60g/day glycine)

43 https://pubmed.ncbi.nlm.nih.gov/19826900/ (2009; "Since the late 1970s, glycine has been considered an important inhibitory NT")

44 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1760744/ (2006; similarities between glycine & GABA as neurotransmitters)

45 https://pubmed.ncbi.nlm.nih.gov/17715569/ (2007; animal study showing glycine having anti-anxiety effects)

46 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933890/ (2018; "taurine has been approved for the treatment of congestive heart failure in Japan"; taurine is the most abundant free amino acid in humans)

47 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2586397/ (2008; taurine in CVD)

48 https://pubmed.ncbi.nlm.nih.gov/28118062/ (2017; taurine in heart failure)

49 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536745/ (2019; taurine & neuro disease, including epilepsy/seizures and neuropathy)

50 www.ncbi.nlm.nih.gov/pubmed/23410665 (2013; in 9 patients w/ epilepsy, seizure disappeared in 5 when taking 1.5-7.5g oral taurine for 2 wks)

51 www.ncbi.nlm.nih.gov/pmc/articles/PMC2997922/ (2010; taurine’s positive effects on tinnitus in an animal model)

52 www.ncbi.nlm.nih.gov/pmc/articles/PMC3501277/ (2012; review of benefits of taurine, including on nervous system, eyes & heart)

53 www.ncbi.nlm.nih.gov/pmc/articles/PMC5615919/ (2016; positive effect of taurine on chronic & acute liver injury)

54 www.ncbi.nlm.nih.gov/pubmed/22918604 (2014; taurine protective against liver disease)

55 www.ncbi.nlm.nih.gov/pmc/articles/PMC3233850/ (2011; taurine supplementation as preventative for NAFLD)

56 www.ncbi.nlm.nih.gov/pubmed/19239160 (2009; rat study; taurine should be considered as therapeutic agent for liver injury & liver fibrosis)

57 https://link.springer.com/article/10.1007%2Fs00726-007-0565-5 (2008; amino acid taurine improves liver in chronic hepatitis patients)

58 https://www.jneurosci.org/content/28/1/106 (2008; taurine is a structural analog of the inhibitory NTs glycine & GABA)

59 https://pubmed.ncbi.nlm.nih.gov/17728537/ (2007; taurine’s anti-anxiety effects)

60 https://pubmed.ncbi.nlm.nih.gov/31468456/ (2019; taurine is essential for the emotional development of the brain; taurine treatment partially improves anxiety-like behavior)