Archive for March, 2018

Supplements for Nerve Pain

Here’s some of the findings from my research into supplements which may help with nerve pain and small fiber neuropathy. Some of the results are based on diabetic neuropathic pain but since my nerve damage pain (from surgery) and my allodynia have responded to one of those already (Alpha Lipoic Acid) it seems worth exploring others. I’m also experiencing anxiety as a new symptom so have paid particular note to that and things like brain chemistry – this is not extensive research and doesn’t cover every aspect.

Some of the information given such as dosage is conflicting. I’m just recording what I’ve found through research and there isn’t always a clear answer. Sorry I didn’t have the energy to link to all the sources for the info I’ve noted.

Updated 24th March 2018

For Nerve Pain:

Alpha Lipoic Acid





Palmitoylethanolamide / PEA



Passion Flower / Passiflora

NAC or N-acetylcysteine

Turmeric / Curcumin


Also important for nerve repair and function:


Omega 3

GLA / Gamma-linolenic acid

Vitamin D

Vitamin B12

Thiamine B1 or Benfotiamine

Vitamin B6

CoQ10 (CoEnzyme Q10)

Alpha Lipoic Acid

Good for:

Nerve pain, allodynia, weight loss, diabetes, anxiety, dementia, healing wounds, migraines


Antioxidant that kills free radicals.

Alpha-Lipoic Acid has been shown to boost acetylcholine (ACh).

May increase nerve regeneration rates secondary to nervous system injury.
The combined robust antioxidant, neuroprotective and especially metabolic actions facilitate strong effect on cognition, memory and delaying mental fatigue.

Improves the function and conduction of neurons in diabetes. Improves the flow of blood to the nerves allowing them to use energy effectively.
Potent antioxidants for biological reactions taking place in the mitochondria of our cells.

Regulating blood sugar and insulin. Improves lipid profiles (cholesterol, triglycerides, and high/low density lipoproteins) and reduces plaque formation in arteries.

Side effects/Risks:

Might get a rash. In humans, doses of 1800mg/day and 2400mg/day failed to have any side effects over a 6-7 month period.
Nausea (deemed minor and related to appetite suppression) and an itching sensation of the skin associated with higher (1,200-1,800mg) doses.
Toxicity at 3-5g of ALA a day inducing mineral deficiencies.
People at risk for thiamine deficiency should take a thiamine supplement (particularly heavy drinkers).
People with diabetes should be careful to check their blood sugar levels because alpha-lipoic acid might lower blood sugar.

Contraindicated with chemotherapy.
May interfere with thyroid medications (can affect the conversion of T4 into T3).

Increased risk of developing (very rare) IAS (insulin autoimmune syndrome) resulting in low blood sugar (hypoglycemia) in individuals with a specific genetic variation – hypoglycemia resolved once the alpha lipoic acid was stopped.

Symptoms of high acetylcholine – ACh can act like a stimulant by releasing norepinephrine (NE) and dopamine (DA).  However, those brain chemicals are used up (depleted) in the process; and a deficiency can occur. Too much ACh relative to other brain chemicals such as serotonin (SE), NE, and DA has an adverse effect on brain function. This is because in larger quantities ACh acts like an inhibitory neurotransmitter, causing increased nervous system inhibition (depression). Important to remember is that, in general, as ACh levels go up in the brain, the levels of the other brain transmitters go down. In terms of mood, the combination of higher ACh and NE, together with lower SE, produces anxiety, emotional lability, irritability, anger, aggressiveness, negative rumination, impatience, and impulsiveness (among other things).


Between 100mg to 600mg per day for its antioxidant benefits.
Neuropathic pain 600mg or 1200 mg daily.
For diabetes or bodybuilding may benefit from higher doses up to 1200mg. High doses should be split and taken throughout the day.

One trial demonstrated at doses of 600mg 3 times daily for a 3 week period led to very significant improvements in neuropathic symptoms. Another trial found that a dose of just 600 mg a day taken for 4 years improved symptoms and slowed down the progression of neuropathy.


Good for:

Nerve pain, anxiety, panic, cholesterol, weight loss, PCOS, OCD


Works in the nerves involved with cellular signaling. Mediates 5-HT (serotonin) activation within nerve cells.

Serotonin, Dopamine, Norepinephrine, and Acetylcholine are primary messengers, transmit messages from one neuron to receptors on another neuron but rely on secondary messengers to complete the signal and relay information within the cells. Inositol is one of the key secondary messengers needed for successful signaling. Inositol, Dopamine, and Serotonin work together to maintain consistent hormonal balances within the brain.

Inositol helps boost serotonin and dopamine receptor density. Improving the effectiveness of serotonin, GABA, glutamate and dopamine neurotransmitters in your brain.

It increases Cholinergic as well as GABAergic activity.

May enhance natural energy, especially when taken just before any activity that will subject the body and mind to stress.

Some of its effects include healthy hair and controlling estrogen levels

Side Effects/Risks:

Water soluble so excess expelled. Minimal side effects. No withdrawal.
Possibly agitation, apathy, brain fog, decreased self-awareness, diarrhea, libido reduction, and sweating.
Can cause nausea, tiredness, headache, and dizziness.
Very safe supplement to ingest, and all side-effects associated with myo-inositol are merely mild gastrointestinal distress from high doses.

Most common side effects are loose stools at the beginning of supplementation, which resolve as your body gets used to inositol. Other reported side effects are nausea, headaches, fatigue and dizziness. Some people also notice increased sweating that usually resolves with time.


500-1,000 mg a day for nerve pain

In the range of 200-4,000mg once daily before breakfast; the higher dose seems to be used more often and seems more effective. Neurological usage of inositol tends to require higher doses, and while antidepressant effects have been noted as low as 6g at times the standard dose is between 14-18g daily

PCOS 4 g per day (divided into 2 grams twice daily)

Anxiety/Panic between 12 grams and 18 grams per day (build slowly)
Depression 12 grams daily. This dose has been shown to improve the symptoms of depression after 4 weeks.


Good for:

Nerve pain, nerve damage, depression, weight loss, blood sugar, muscle disorder, heart conditions, cholesterol, hyperthyroidism


An amino acid that improves diabetic neuropathy. Supplementing with carnitine might help increase insulin resistance, allow the cells to utilize glucose effectively and boost nerve regeneration.

Alleviates symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy.
It works to regenerate myelin sheathing of nerves, produce new nerve fibers, and improve the function of important nerve connections to organs.

Glutamate is a neurotransmitter that is significantly involved in pain transmission including neuropathic pain.  Glutamate receptors are proteins that bind to glutamate for supporting its function. These receptors when activated relieve neuropathic and inflammatory pain. Acetyl-l- carnitine activates with these glutamate receptors to relieve neuropathic pain.

Acetyl L-carnitine acts as an antioxidant. Able to cross the blood-brain barrier.
Supports acetylcholine and dopamine levels. Increases norepinephrine in the hippocampus and serotonin in the cortex. Supporting norepinephrine and serotonin in the brain can help with depressive symptoms as well as cognitive deficits.May reduce amounts of GABA and increase myo-inositol . May alter monoamine neurotransmitter levels.

Side Effects / Risks:

Diarrhea, nausea, stomach pain, vomiting. Headaches. Over-stimulation. Trouble sleeping. Raise blood pressure. Lower blood sugar and higher triglycerides (in people with diabetes). Psychosis in people with bipolar disorder.

May increase the risk of seizures in those with epilepsy.

Warnings for people with hypothyroidismperipheral vascular disease, high blood pressure, liver cirrhosis, alcoholism, diabetes, kidney failure, digestive problems, risk factors for mental illness, hepatitis C (fatigue may worsen).

Warning with blood-thinning drugs, beta-blockers, calcium-channel blockers. May interact with drugs or supplements that lower blood sugar. It may affect how your body breaks down certain drugs and supplements.


500 mg or 1,000 mg three times daily

As per the research studies, the beneficial dose of acetyl-L-carnitine is 1000-2000mg daily. Start with a small dose (500mg daily) and scale up gradually; a dose of 1000mg -1500mg per day should help.


Good for:

Nerve Pain, Anxiety, Sleep, lowering blood pressure, cholesterol


Naturally occurring amino acids. L-Theanine increases brain serotonin, dopamine, and GABA levels.

A mild stimulant for glutamate receptors and keeps glutamate from full activation, which acts to tame excitotoxicity.

Increases alpha brain wave activity, especially for those people who suffered from prior anxiety. Brain waves are actually smoothed out—but not flattened out.

Prevents the abrupt rise in blood pressure that some people experience under stress.

Unlike prescription anti-anxiety drugs, L-theanine relieves stress without causing drowsiness or impairing motor behavior. In fact, studies show it improves alertness and attention.

Theanine may boost the activity of T cells that protect against infection and tumors.

Side Effects/Risks:

More likely to occur at higher doses. Headaches. Dizziness. Reduction of appetite. Lowering blood pressure. Slight gastrointestinal discomfort.  Nausea.

Very high doses of L-Theanine may result in a fairly strong sedative effect.

As it  it indirectly interacts with GABA receptors you may want to avoid using a Theanine GABA combination.

While L-theanine also has the potential to increase serotonin levels in the brain, it has occasionally been shown to decrease them as well.

Contraindicated in chemotherapy.


For neuropathy 200 mg three times a day, taken 30 minutes before meals. This can be increased to 400 mg three times a day if needed.
For anxiety 200mg two to three times daily


Good for:

Chronic Pain, Depression, Vitiligo, (ADHD), Parkinson’s disease


DL-Phenylalanine is a combination of D-Phenylalanine and L-Phenylalanine, two different forms of Phenylalanine. D-Phenylalanine is a laboratory-made substance that has been studied for potential pain-relief effects. It has great effects and is especially useful in supporting your natural pain-relief system. L-Phenylalanine is an essential amino acid and is required for your body to function correctly. L-Phenylalanine deficiency is linked to lowered mood and feelings of stress. Higher doses of L-Phenylalanine may have the potential to improve your mood and focus.

DL-phenylalanine appears to improve chronic pain symptoms through up-regulation of your endogenous analgesia system. Your EAS is a neural system that suppresses nerve transmissions in your pain pathways. Thus, the EAS is responsible for reducing pain sensations.

Inhibits the breakdown of endorphins. Endorphins are pain-relieving compounds that originate within your body.

Phenylalanine is needed to produce certain neurotransmitters, including dopamine and serotonin.

Research has indicated that migraine, joint pains, neuralgia and even postoperative pain respond to DLPA, and it has been reported to reduce inflammation. DLPA does not deaden normal sensation even when taken for a lengthy period.

Side Effects/Risks:

Very well tolerated and for the most part side effects free. DL-phenylalanine side effects include nausea, headaches and heartburn. Both DLPA and l-phenylalanine can cause migraines or slightly increase blood pressure.

Some common side effects include anxiety, jitteriness, or hyperactivity.

Rare side effects can include itching, mouth tingling, or swelling of the hands of the feet (these are rare).

Can worsen tardive dyskinesia — involuntary movements — if you are currently taking anti-psychotic medication. You should not take DL-phenylalanine if you are on anti-psychotic medication. DL-phenylalanine may interact with a class of antidepressants known as monoamine oxidase inhibitors.

Contraindicated for Levodopa used for Parkinson’s disease, MAOIs, medications for mental conditions might cause jerky muscle movements.


The most common range is 750mg to 3,000 mg daily. Studies have shown highest efficacy for depression utilized doses of 50mg to 200 mg per day.

The dose of DLPA needed may vary from person to person, and is generally determined by starting with perhaps 1,000 mg daily for two weeks and then gradually increasing to a level that provides relief. If 3,000 mg per day doesn’t work after a month’s time, it probably will not work at all. The good news is that persons reporting pain relief will generally be able to LOWER their dose gradually and will often be able to maintain pain-free status with less DLPA than before.

Palmitoyalethanolamide aka PEA

(Not to be confused with Phenylethylamine which is also known as PEA)

Good for:

Chronic Pain, Nerve Pain, Joint Pain, Migraine, Fibromyalgia, Chronic Regional Pain Syndrome (CRPS), Small Fiber Neuropathy,


Naturally occurs in the body. It stops pain and inflammation, protects the heart, and improves brain function. Pain suppressant and anti-inflammatory. Clinical trials have found that the compound’s action performs numerous biological functions related to chronic pain.

It has been found to have anti-inflammatory, anti-nociceptive, neuroprotective, and anticonvulsant properties.

Binds to a receptor responsible for regulating the gene networks connected to the control of pain.

While PEA is not technically an endocannabinoid, it often gets grouped into the family; particularly with anandamide, because PEA operates via similar metabolic and synthetic pathways.

PEA is the key to suppressing overactive mast cells. Mast cells release inflammatory histamine and cytokines into the body.

The action mechanism of PEA is strengthened by complementary action mechanisms of the selected B vitamins.

Studies with mice using PEA found less injury to heart tissue, decreased cell death, and lower levels of cytokines.

Side Effects/Risks:

To date, no drug interactions have been reported in the literature, nor any clinical relevant or dose-limiting side effect.

Rarely gastrointestinal upset and diarrhea with the sublingual preparation, probably due to the sorbitol in it. No side effects with PeaPure.

No adverse reactions with other commonly used pain relievers such as tramadol, pregabalin, gabapentin, amitriptyline, and duloxetine.


6 weeks with 600 mg tablets twice daily. Once 50% reductions in pain are seen reduces the dose to 300 mg twice daily.

or: CRPS: Start 3 x 400mg either over 3 doses or split into 2 in morning and 1 in evening. After some weeks you could increase to 6 x 400mg

The analgesic effects are build up day by day; most people notice the effects within 1 week, but sometimes 6-8 weeks is required, especially for chronic pain syndromes.

PeaPure:  It has been proved that taking 1 capsule of 400 mg 3 times a day during the first 2 months is a good starting dosage. PeaPure users usually notice an improvement during the first few weeks.  Only after two months, the effectiveness of PeaPure can be properly evaluated. From that moment on it will become clear whether it is worthwhile to continue to take PeaPure for a prolonged period of time. If, after 2 months, the desired effect has been achieved, the dosage can be reduced to 1 capsule of 400 mg 2 times a day.

Starting from 4 months you can consider:
–    to continue the dosage of 1 capsule 2 times a day
–    to reduce the dosage to 1 capsule 1 time a day
–    to stop taking PeaPure.

If the result decreases after reducing the dosage, it is advisable to increase the dosage again to 1 capsule 2 or 3 times a day.

or: General palmitoylethanolamide dosing guidelines are as follows:

  • Initial dose: 1200 mg per day, with or without food, for the first 6 weeks.
  • Maintenance dose: 600 mg per day, with or without food.


Good for:

Anxiety, Insomnia, fibromyalgia, sugar/carb cravings, binge eating, migraines, PMS, dementia


The amino acid, L-tryptophan, carries information throughout the nervous system and promotes emotional calmness. Our bodies convert it to 5-HTP (5-hyrdoxytryptophan), and then to serotonin, melatonin, and vitamin B6 (nicotinamide).

Serotonin is an important neurotransmitter with a major role in sleep, pain, and appetite, and it affects conditions like depression and anxiety. It influences pain thresholds through interacting with other compounds involved in the sensation of pain, like substance P and endorphins.

Side Effects/Risks:

Drowsiness, agitation, nausea, dizziness, headache,  lightheadedness, loss of appetite and muscle tenderness, gut symptoms,

Between 1988-1999, an EMS outbreak prompted the FDA to recall and cease over-the-counter tryptophan supplements. However, this was because one company in Japan that made synthetic tryptophan altered their creation process, which caused the outbreak. After this was caught and fixed, the FDA lifted the ban in 2001

Contraindicated for MAOI, iproniazid, liver disease, kidney disease. Anti-cough drugs such as dihydrocodeine, noscapine, and dextromethorphan increased cough resistance.


  • for sleep disorders/insomnia: 1–2 grams taken at bedtime
  • for chronic pain or migraines: 2–4 grams per day in divided doses
  • for treating PMS or PMDD: 2–4 grams daily
  • for helping to alleviate depression or anxiety: 2–6 grams daily (it’s best to work with a doctor)
  • for lowering appetite and cravings: 0.5–2 grams daily

While the usual dosage of L-tryptophan is 500 mg, many people take more and supplement’s instructions recommend 3 pills before bedtime.

Less than 8 grams per day for 8 weeks shouldn’t produce any side effects.However, an upper limit for tryptophan supplementation is still uncertain


Good for:

Nerve pain, allodynia, anxiety, cholesterol, lowering blood pressure, arthritis, diabetes or prediabetes


Suppresses currents along sodium channel for analgesic effect. Inhibits inflammation. Regulates levels of nerve growth factors and lowers oxidative stress.
Known to stimulate norepinephrine release at a moderate level. Resveratrol is also an MAO-Inhibitor and a serotonin agonist. As such, it may improve mood, reduce anxiety and even lead to better sleep quality. Promote better circulation.

Side Effects/Risks:

At high doses, it may cause gastric side effects such as nausea and diarrhoea. One study has noted side effects such as a headache, skin rash and common cold-like symptoms.
Caution in bleeding disorders.

Blocks some enzymes that help clear certain compounds from the body. That means some medications could build up to unsafe levels. These include certain blood pressure medications, anxiety meds and immunosuppressants.

In some situations, high doses of resveratrol boost the activity of estrogen, in others they block estrogen. That makes resveratrol supplements iffy for women with cancer of the breast, ovary, uterus, or other estrogen-sensitive tissue, those trying to become pregnant, or those taking an oral contraceptive.


500-1000mg daily of resveratrol has been evaluated in clinical studies.

Typically taken in about 250 to 500 milligrams/day dosages. It’s important to point out that this is generally lower than the amounts that have been shown to be beneficial in studies, but it’s not clear if taking very high doses is safe.

Passion Flower / Passiflora

Good For:

Nerve pain, allodynia, anxiety, Fibromyalgia, sleep, Parkinsons, lowering blood pressure, menopause (hot flashes/night sweats)


Increases levels of gamma aminobutyric acid (GABA) in the brain. Contains compounds called beta-carboline harmala alkaloids which act as natural MAO (monoamine oxidase) inhibitors. MAO inhibitors aid in the metabolism of feel-good neurotransmitters serotonin and norephinephrine.
Shown to have anti-inflammatory, anticonvulsant and antispasmodic properties.

Side Effects/Risks:

Drowsiness. Dizziness, confusion, irregular muscle action and coordination, altered consciousness, and inflamed blood vessels. There has also been a report of nausea, vomiting.
More serious side effects include irregular heartbeat, loss of coordination and liver damage
Passionflower can affect the central nervous system. It might increase the effects of anesthesia and other medications on the brain during and after surgery.
Contraindicated with sedative medications, blood thinners, MAOs and blood pressure medication


The capsules usually come in 200-400 mg doses taken two to three times a day.
Between 250 mg to 2,000 mg of the raw herb three times daily.

For anxiety 200-300 mg of a standardized extract, twice a day.

NAC or N-acetylcysteine

Good for:

Nerve pain, cholesterol, CRPSAction:
Increase glutathione synthesis in the liver. Fights oxidative stress. Reduces inflammation.  Regulates neurotransmitter levels. Normalises mitochondrial function, which can repair and restore nerve function in case of nerve damage.

Side Effects/Risks:

Adverse reactions are normally limited to diarrhea, headache, nausea and/or vomiting
Contraindicated kidney stones and stomach ulcer. Contraindicated with nitroglycerin.

Warning for bleeding disorders.


About 500 mg to 1800 mg per day . Two human studies have used 1200mg N-acetylcysteine 1-2 times a day for peripheral neuropathy and neuropathic pain treatment. High dose NAC can have side effects; the dose range of 2-2.4g/day is safe and effective in most conditions. Start with a small dose and increase gradually to identify a dose that suits you.

Most research also indicates that it is essential to take 500 mg of Vitamin C to prevent kidney stones.

Turmeric / Curcumin

Good for:

Allodynia, nerve pain, anxiety, depression, arthritis, IBS


Antinociceptive pain blocking in neurons. Anti-inflammatory and antioxidant properties. Epigenetic agent having a positive impact on gene expression primarily by influencing methylation.
Elevates neurotransmitters such as serotonin, while lowering stress hormones, such as cortisol.

Side Effects/Risks:

Some research suggests the potential for liver toxicity. Possible side effects possible (at high doses) is gastric discomfort such as nausea, diarrhoea, constipation, bloating .
High in oxalates which is bad for kidney stones.
Warning for bleeding disorders.

Hyperactive gallbladder contractions.

Increased liver function tests.

Interacts with drug metabolising enzymes; please maintain a 3-4 hour gap between taking curcumin and any medication.


300-400mg 2-3 times a day for standardized 95% curcumin extract.
Neuropathy 500-1000mg of standardised 95% curcumin. Start with small doses such as 500mg per day for a week and then scale up gradually every week. Doses up to 8g have been found to be safe but a dose of 2g per day should suffice for severe cases.


Good for:

Nerve pain, allodynia, inflammation, allergies, cholesterol, heart disease, lowering blood pressure, prostrate


Fights oxidative stress. Inhibits inflammation. Can regulate immune responses and serve as a natural immunosuppressant in some conditions.
Can help in regeneration of nerve cells and promote neurite growth.
Civi et al. have found quercetin to be more effective than gabapentin and morphine in relieving nerve pain in a model of nerve constriction injury.

Side effects/risks:

Can cause headache and tingling of the arms and legs.

Please maintain a 3-4 hour gap between taking quercetin and any medications.
It may interact with certain medications: antibiotics, felodipine, quinolones, cisplatin, doxorubicin, digoxin, cyclosporine, corticosteroids and blood thinners.
Doses higher than 1g may cause kidney toxicity. It is advisable to take periodic breaks when taking quercetin supplements.


Depending on the severity of symptoms, 500-1000mg of quercetin for neuropathy.

Start with smallest dose available (250 or 500mg) and scale up gradually over weeks. Doses higher than 1000mg are not recommended. Cycling the dose or taking a break from quercetin intermittently is advised.
Quercetin supplements can be taken with other flavonoids such as curcumin, resveratrol or green tea catechins to get the benefits at a reduced dose.


Also Useful…

involved in muscle contraction, nerve conduction and muscle relaxation. May help relieve nerve pain by blocking certain pain receptors and acting as an anti-inflammatory in order to regulate pain.

Omega 3
building blocks of nerve tissue and are useful at high doses (6 grams daily) to reduce nerve inflammation.

GLA / Gamma-linolenic acid
omega-6 oil that has been studied and found to protect nerves from diabetes-induced injury high in evening primrose, borage and black currant oils. Anti-inflammatory

Vitamin D
can help to reduce the pain and inflammation associated with neuropathy, along with actually repairing the nerves and myelin sheath. Enhances the absorption of important minerals. Held to be integral to the healthy production and protection of neurotransmitters and other nervous system tissues.

Thiamine B1 or Benfotiamine
benfotiamine modulates the pathways that cause neuropathy. It regulates cellular damage caused by high levels of glucose and prevents vascular problems that also contribute to neuropathy. Several trials have demonstrated that benfotiamine taken at doses between 300 and 600 mg a day can significantly relieve the symptoms of diabetic neuropathy. Benfotiamine is often prescribed in Germany as a treatment for sciatica and other neuropathic pain complaints.

Vitamin B6
Benefits nerve function and synthesizes neurotransmitters like serotonin and dopamine

Vitamin B12
Vitamin B12 can extenuate nerve damage caused by neuropathy by activating a chemical signal, which helps nerves to regenerate. Restores blood flow which produces myelin synthesis, a fatty substance that protects the nerve fibers. Combinations of Vitamin B12 and 6 (methylcobalmin, folic acid and pyridoxal) have been found to improve symptoms and maintain the health of nerves in the extremities. Deficiency in B12 can contribute to peripheral neuropathy.

CoQ10 (CoEnzyme Q10)
plays an important role in addressing mitochondrial dysfunction, a condition that may result in nerve damage and pain. This supplement is also effective at neutralizing the threat of free radicals in the body.

needed for the transmission of nerve signals between the brain and body

essential for normal nerve function



Push It 11 Sep 2011

for ME Research

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