HW functional medicine · 11 min read · 2,168 words

Amino Acids: The Building Blocks of Healing

DNA is the blueprint. Amino acids are the bricks.

By William Le, PA-C

Amino Acids: The Building Blocks of Healing

The Alphabet of Life

DNA is the blueprint. Amino acids are the bricks. Every protein in your body — every enzyme, neurotransmitter, hormone receptor, immune antibody, structural tissue — is built from just 20 amino acids arranged in different sequences. Change one amino acid in hemoglobin and you get sickle cell disease. The precision matters.

In functional medicine, amino acid therapy is one of the most underutilized tools in the kit. Instead of prescribing SSRIs, you can provide the serotonin precursor. Instead of sedatives, you can supply the GABA precursor. Instead of immune suppressants, you can repair the gut barrier with glutamine. This is targeted molecular medicine using the body’s own building materials.

Understanding amino acids is understanding the language of biochemistry itself.


Classification: Essential, Conditional, and Non-Essential

Essential (9): Must come from diet — histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine.

Conditionally essential: Normally synthesized but become essential under stress, illness, or inadequate precursors — arginine, cysteine, glutamine, glycine, proline, tyrosine.

Non-essential: Synthesized by the body in adequate amounts under normal conditions — alanine, asparagine, aspartate, glutamate, serine.

The “conditional” category is where functional medicine lives. During chronic illness, surgery, trauma, or heavy physical demand, the body’s synthesis cannot keep up with demand. Supplementation shifts from optional to therapeutic.


Part 1: Neurotransmitter Precursors

L-Tyrosine: Fuel for Drive and Focus

Tyrosine is the precursor to the catecholamine pathway: tyrosine → L-DOPA → dopamine → norepinephrine → epinephrine. This is the pathway of motivation, focus, pleasure, and stress response. Tyrosine is also required for thyroid hormone synthesis (tyrosine + iodine = T4/T3).

Clinical dosing: 500-2000mg, taken in the morning on an empty stomach (competes with other large neutral amino acids for BBB transport).

Applications: Low dopamine states (apathy, poor motivation, difficulty concentrating, brain fog), adrenal support during stress recovery, adjunct for ADHD, thyroid support.

Contraindications: Hyperthyroidism (provides thyroid hormone substrate), MAOIs (can precipitate hypertensive crisis), migraine triggered by tyramine-rich foods (crossover sensitivity). Monitor in bipolar disorder — can trigger mania through dopamine elevation.

L-Tryptophan: The Serotonin Seed

Tryptophan is the precursor to serotonin, which is then converted to melatonin. This single amino acid governs both daytime mood and nighttime sleep architecture.

Clinical dosing: 500-1000mg at bedtime, away from protein-rich meals (competition for BBB transport).

The kynurenine steal: Under inflammatory conditions, the enzyme IDO shunts tryptophan away from serotonin production and into the kynurenine pathway — producing quinolinic acid (neurotoxic) instead of serotonin. This is a key mechanism linking chronic inflammation to depression. Addressing inflammation can restore tryptophan routing to serotonin.

Tryptophan vs 5-HTP: Tryptophan must pass through the rate-limiting enzyme tryptophan hydroxylase (TPH) before becoming 5-HTP, then serotonin. 5-HTP bypasses this step. Both work; tryptophan is gentler and more physiological, 5-HTP is faster-acting.

SSRI interaction warning: Combining tryptophan or 5-HTP with SSRIs increases serotonin syndrome risk — tremor, agitation, hyperthermia, myoclonus, potentially fatal. Use only under careful clinical supervision when combining.

5-HTP (5-Hydroxytryptophan): The Direct Serotonin Precursor

5-HTP is one enzymatic step from serotonin. Derived from the African plant Griffonia simplicifolia.

Clinical dosing: 50-200mg, typically at bedtime. Start low (50mg) and titrate.

Applications: Insomnia (enhances sleep onset and quality through melatonin conversion), mild-moderate depression, appetite suppression, fibromyalgia pain modulation.

Clinical pearl: 5-HTP can deplete dopamine and norepinephrine if used long-term without catecholamine precursor support. The enzyme AADC (aromatic amino acid decarboxylase) that converts 5-HTP to serotonin also converts L-DOPA to dopamine — 5-HTP can monopolize this enzyme. Consider pairing with L-tyrosine for balance during extended use (Hinz 2012).

Serotonin syndrome risk with SSRIs: Same warning as tryptophan. This is the most clinically important interaction to remember.

GABA (Gamma-Aminobutyric Acid): The Brake Pedal

GABA is the brain’s primary inhibitory neurotransmitter — it slows neural firing, reduces anxiety, promotes relaxation, and facilitates sleep. Every benzodiazepine works by enhancing GABA receptor activity.

Clinical dosing: 500-750mg.

PharmaGABA vs synthetic: PharmaGABA is produced by Lactobacillus hilgardii fermentation and may be better absorbed. The blood-brain barrier debate persists — conventional neuroscience says GABA doesn’t cross the BBB, yet clinical results clearly show CNS effects. Current thinking: it may work through the enteric nervous system (gut-brain axis), through peripheral GABA receptors, or through limited BBB passage in areas of increased permeability.

L-Theanine: Calm Without Sedation

Theanine, found naturally in green tea (Camellia sinensis), modulates GABA, increases alpha brain wave production (the “relaxed alertness” pattern), and buffers glutamate excitotoxicity.

Clinical dosing: 100-400mg. Can be taken anytime — does not cause drowsiness despite promoting relaxation.

Applications: Anxiety (without sedation), focus enhancement (stacks with caffeine for clean alertness — the “green tea effect”), sleep onset (200-400mg at bedtime), stress resilience.

Why green tea calms despite caffeine: The L-theanine content (25-60mg per cup) modulates caffeine’s stimulatory effect. Matcha has even higher theanine. This is why tea produces a different quality of alertness than coffee.


Part 2: Gut and Immune Amino Acids

L-Glutamine: The Gut Healer

Glutamine is the primary fuel source for enterocytes (gut lining cells) and lymphocytes (immune cells). During illness or gut damage, glutamine demand skyrockets beyond what the body can produce — making it conditionally essential in every sense.

Clinical dosing: 5-15g daily, typically in powder form dissolved in water. For intensive gut repair: 5g three times daily.

Applications: Leaky gut repair (maintains tight junction integrity), IBS symptom reduction, post-antibiotic gut restoration, sugar and alcohol craving reduction (glutamine provides alternative fuel for the brain when glucose is low), exercise recovery (immune suppression from heavy training — Castell 1996).

Cautions: Cancer cells also preferentially use glutamine as fuel — avoid in active malignancy. Theoretical concern in seizure disorders (glutamine converts to glutamate, the excitatory neurotransmitter). In practice, most clinicians find this theoretical risk does not manifest at standard doses.

N-Acetyl Cysteine (NAC): The Glutathione Gateway

NAC is the rate-limiting precursor for glutathione — the body’s master antioxidant and primary detoxification molecule. Every cell produces glutathione from three amino acids: cysteine (the bottleneck, which NAC provides), glutamine, and glycine.

Clinical dosing: 600-1800mg daily in divided doses.

Applications:

  • Glutathione precursor: The most cost-effective way to raise intracellular glutathione.
  • Mucolytic: Thins mucus (FDA-approved for this use). Useful in respiratory conditions, sinusitis, COPD.
  • Biofilm disruptor: Breaks bacterial biofilms (Marchese 2003). Adjunct in chronic infections, SIBO, Lyme.
  • Acetaminophen antidote: Standard emergency room treatment for Tylenol overdose — replenishes glutathione that acetaminophen depletes.
  • Psychiatric applications: OCD (Costa 2017 — adjunct to SSRIs), addiction (cocaine, cannabis), trichotillomania, bipolar depression. Mechanism: glutamate modulation and oxidative stress reduction.
  • Liver protection: Supports Phase 2 detoxification, protects against alcohol damage.

Glycine: The Simple Giant

Glycine is the smallest amino acid and one of the most versatile. Three grams at bedtime improves sleep quality as effectively as many sleep medications — the Inagawa 2006 study showed improved sleep quality, reduced daytime sleepiness, and enhanced cognitive performance the next day.

Clinical dosing: 3-5g (sleep), up to 10g for therapeutic applications.

Applications:

  • Sleep: 3g before bed — works through peripheral vasodilation and core temperature drop, mimicking the body’s natural sleep onset physiology.
  • Collagen synthesis: Glycine is the most abundant amino acid in collagen (every third residue). Supplementation supports joint, skin, and connective tissue repair.
  • Phase 2 detoxification: Glycine conjugation is a major Phase 2 liver pathway. Handles benzoate, salicylate, and many other compounds.
  • Glyphosate displacement: A hypothesis gaining traction — glyphosate (Roundup) may substitute for glycine in protein synthesis due to structural similarity (Samsel and Seneff 2013). Glycine supplementation theoretically provides the correct building block. Debated but biologically plausible.

Part 3: Performance and Recovery

BCAAs (Branched-Chain Amino Acids)

Leucine, isoleucine, and valine — the three branched-chain amino acids — comprise roughly 35% of muscle protein and are uniquely metabolized in muscle rather than liver.

Leucine is the key — it activates mTOR, the master switch for muscle protein synthesis (MPS). The “leucine threshold” (Katsanos 2006) requires approximately 2.5-3g of leucine per meal to maximally stimulate MPS. This is why protein quality matters: 30g of whey hits the threshold, but 30g of plant protein may not without intentional combining.

Supplement vs whole food: Whole protein sources provide the full amino acid spectrum plus leucine. BCAA supplements are useful during fasted training, for elderly patients with appetite issues, or when total protein intake is insufficient. For most well-fed individuals, whole food protein is superior.

L-Carnitine / ALCAR (Acetyl-L-Carnitine)

Carnitine transports long-chain fatty acids into mitochondria for beta-oxidation — without it, your cells cannot burn fat for fuel. Think of carnitine as the ferry that carries fat across the mitochondrial membrane.

Clinical dosing: 1-3g daily.

  • L-Carnitine tartrate: General energy, exercise recovery, heart support.
  • Acetyl-L-Carnitine (ALCAR): The acetyl group crosses the blood-brain barrier and donates acetyl groups for acetylcholine production. Best for cognitive function, neuropathy, brain aging.

Applications: Mitochondrial dysfunction/fatigue, heart failure (improved exercise capacity), male fertility (improves sperm motility and morphology — Lenzi 2004), diabetic neuropathy, cognitive decline, exercise performance.

Creatine Monohydrate: Not Just for Athletes

Creatine is one of the most researched supplements in history — safe, effective, and far more versatile than its gym-bro reputation suggests. It recycles ATP, the universal energy currency of cells.

Clinical dosing: 5g daily (no loading phase necessary).

Applications beyond muscle: Brain energy (Rae 2003 — improved working memory and intelligence under stress), elderly sarcopenia prevention (Candow research — combined with resistance training, creatine significantly improves lean mass and strength in seniors), depression adjunct, TBI recovery, mitochondrial disease support.

Vegetarians consistently show greater cognitive improvement from creatine supplementation — likely because they get zero dietary creatine (found only in meat).

D-Ribose: ATP Recovery

D-Ribose is a five-carbon sugar that forms the backbone of ATP. When cells are energy-depleted (chronic fatigue, fibromyalgia, heart failure), ATP pools take days to rebuild. D-ribose provides the raw material to accelerate this recovery.

Clinical dosing: 5g three times daily (Teitelbaum protocol for CFS/fibromyalgia). The Teitelbaum 2006 study showed 66% of CFS/fibromyalgia patients improved significantly with D-ribose supplementation.

Applications: Chronic fatigue syndrome, fibromyalgia, post-exercise recovery, heart failure (Pliml 1992 — improved cardiac function), any state of cellular energy depletion.


Part 4: Other Clinical Amino Acids

L-Arginine / L-Citrulline: The Nitric Oxide Pathway

Arginine is the substrate for nitric oxide synthase (NOS), producing nitric oxide (NO) — the molecule that dilates blood vessels, regulates blood pressure, supports immune function, and enables erections.

The citrulline advantage: Arginine is heavily metabolized by arginase in the gut and liver (first-pass effect). L-citrulline bypasses this — it converts to arginine in the kidneys, providing sustained NO production. Citrulline (3-6g) raises plasma arginine more effectively than arginine itself.

Applications: Erectile dysfunction (the natural mechanism Viagra amplifies), hypertension, exercise performance (reduced oxygen cost — Bailey 2009), wound healing, Raynaud’s phenomenon.

Taurine: The Cellular Stabilizer

Taurine is the most abundant free amino acid in the heart, brain, and retina. It’s not incorporated into proteins — instead, it functions as an osmolyte (regulates cell volume), membrane stabilizer, bile acid conjugator, and GABA-ergic calming agent.

Clinical dosing: 1-3g daily.

Applications: Cardiovascular health (antiarrhythmic, blood pressure reduction, heart failure support), bile production (critical for fat digestion), anxiety and seizure modulation (GABA-mimetic), magnesium retention (taurine helps cells hold onto magnesium), exercise performance (Rutherford 2010), eye health (retinal protection).

Energy drinks contain taurine for a reason — though the amounts (typically 1g) are therapeutic, the sugar and synthetic ingredients in most energy drinks negate the benefit.

D-Mannose: The UTI Preventer

D-Mannose is a simple sugar that is not metabolized — it passes intact into urine, where it coats the bladder wall and prevents E. coli adhesion (E. coli uses mannose-binding lectins called FimH to attach).

Clinical dosing: 2g twice daily for prevention. The Kranjcec 2014 randomized trial showed D-mannose (2g daily) was as effective as nitrofurantoin antibiotic prophylaxis for preventing recurrent UTIs, with far fewer side effects.

Applications: Recurrent UTI prevention and acute UTI support (alongside antibiotics if needed). Specific for E. coli UTIs (which represent 80-90% of UTIs). Not effective for Klebsiella, Proteus, or other organisms.


The Amino Acid Assessment

In functional medicine, amino acid status is evaluated through:

  • Plasma amino acid panel: Measures 40+ amino acids. Reveals deficiencies, imbalances, and metabolic blocks.
  • Organic acids test (OAT): Indirect assessment — organic acid metabolites reflect amino acid metabolism (e.g., xanthurenate elevation indicates B6/tryptophan metabolism issues).
  • Neurotransmitter testing (urinary): Controversial but sometimes useful for baseline assessment.

The pattern matters more than any single value. Low tyrosine with low phenylalanine suggests protein maldigestion. Low tryptophan with elevated kynurenine metabolites suggests inflammatory shunting. Low glycine with elevated environmental toxin metabolites suggests Phase 2 conjugation demand.

Amino acid therapy is molecular precision medicine. You are providing the exact substrates the body needs to build its own neurotransmitters, repair its own tissues, and run its own detoxification pathways. No pharmaceutical can replace what the body builds for itself — given the right materials.

When you give the body the building blocks it needs, what is it capable of constructing?