I am torn between Th1 and Th2 boosters because I know how well corticosteroids (Th2 boosters) help autistic children and how bad vaccines (Th1 boosters) are. I am still scared to try some heavy Th1 boosters. So, I will need to downselect from that long list of Th1 boosters. My criteria will be:
1. Boost natural killer (NK) cells to fight viral infections and tumors (NK cells are activated by IL-2, IL-12 and other cytokines), which is what I will define as 'Th1 boost'. On the other hand, I will require these NK/Th1 boosters to be anti-inflammatory in the sense that they suppress pro-inflammatory cytokines TNF-alpha and IL-6.
2. Don't reduce seizure threshold and preferably stabilize EEG.
3. Don't increase glutamate and preferably increase GABA.
4. Help to reduce schizophrenia symptoms, which means they don't mess with Dopamine receptors, or neutral
5. Encourage blood circulation or improve cognition in other ways.
6. Help to reduce behaviors like irritability and SIB. For my son, who has MAO-A homozygous mutation, it means that the 'Th1 booster' should not inhibit MAO-A and preferably not inhibit COMT.
7. Non-toxic to liver (doesn't elevate liver enzymes and preferably reduces them) or kidneyThings that passed all of my 7 requirements:
Cordyceps sinensis mushroom
1. Boosts NK cell activity, inhibits IL-1β, IL-6, IL-8, IL-10, TNF-α, NO, and prostaglandin E2 (PGE2) in vitro and in vivo, increases IL-2.
2. can cause convulsions at very high doses
3. Adenosine from Cordyceps protects against glutamate toxicity
4. Increases dopamine
5. Known as nootropic
6. Stabilizes blood sugar levels, so theoretically it should reduce mood swings. However increased irritability and restlessness are some of the reported side effects.
7. Safe (LD50 = 21g/kg), can be eaten as food, protects liver by reducing its enzymes (ALT and AST). However, there were reported cases of lead poisoning from Cordyceps.
Lion's Mane mushroom/Hericium erinaceus
1. Enhances NK cell function, reduces IL-1β, IL-6, and TNF-alpha, downregulates iNOS, regenerates nerves by stimulating NGF
2. effect on seizures is not reported
3. effect on glutamate is not reported but Lion's Mane is considered neuroprotective
4. Used in combination with antipsychotics to restore cognitive function in schizophrenia patients (these drugs reduce NGF). However, a conflicting view on the role of NGF in schizophrenia exists, according to which "the increase in BDNF and particularly NGF may have an important role in causing schizophrenia. And possibly drugs clozapine and risperidone help to treat the disease by reducing the concentration of Neurotrophins"(http://onlinelibrary.wiley.com/doi/10.1111/sji.12158/pdf
5. Increases cognitive function by stimulating NGF, improves focus and attentiveness to one’s surroundings, and thus, should increase learning and motivation, while promoting voluntary interactions with others. Lion’s Mane is the only mushroom to date that was found to have any stimulatory effect on the nerve growth factor (NGF), which makes it very useful to treat brain injuries.
6. positive effect on mood
7. Low toxicity, can be eaten as food, may elevate liver enzymes
1. Significantly enhances NK cell activity, IL-2 and IFN-gamma production in both normal as well as tumor-bearing animals, activates Nrf2, inhibits TNF-α, IL-1β, IL-6, and IL-8. Thanks to Nrf2 activation, Sulforaphane, when administered following traumatic brain injury (TBI), has been demonstrated to attenuate blood-brain barrier permeability, reduce cerebral edema, and restore cognitive function. Sulforaphane and broccoli sprouts are the most promising in preventing and killing cancer out of all of studied natural substances.
2. Theoretically, cellular activation by sulforaphane might exacerbate seizures in patients with known seizure disorders. A trial of sulforaphane in young autistic adult males, a seizure occurred in each of 2 participants: one during treatment (in a participant with a previously undisclosed seizure), the other 3 weeks after discontinuing sulforaphane. However, Sulforaphane is a strong HDAC inhibitor, which is supposed to make it a good mood stabilzer and anti-epileptic just like Valproic Acid.
3. protects against glutamate-mediated excitotoxicity
4. improves cognitive function in patients with schizophrenia. Currently two clinical trials are under way to investigate Sulforaphane as a treatment of schizophrenia.
5. Improves cognition thanks to activiation of Nrf2 and inhibition of HDAC (HDAC inhibitors are currently studied for Alzheimer's
6. Improves mood
7. Low toxicity, may slightly increase liver enzymes
Chinese Thorowax Root/Bupleurum chinense
1. prevents IL-1, IL-6, TNF, IL-8 release and prostaglandin E2 synthesis, exhibits anticancer effects via autophagy induction
2. key herb of traditional chinese medicine for seizures
3. prevents higher glutamate and GABA expressions and contains them within normal range
4. blocks D2 dopamine receptors similarly to atypical antipsychotics Risperidone, Aripiprazole, etc. One of the ingredients of TCM for Scizophrenia.
5. inhibits AChE and can potentially imrve memory and cognition. One study compared TCM containing Bupleurum against Ritalin on chidlren with "brain dysfunction". The TCM group showed 86% effective rate, whereas the Ritalin group showed 90% effective rate. But the TCM group had less side effects and had their EEG normalized or improved. Other herbs in the TCM formula were Chinese Skullcap, Astragalus, Codonopsis pilosula (poor man's ginseng), Ligustrum lucidum, Lophatherum gracile, and thread of ivory.
7. Low toxicity (LD50 = 1.2g/kg), one of the key herbs in detoxing and healing liver
1. Boosts NK, kills leukemia cells and is also anti-inflammatory (reduces IL-6 and TNF-α, activates Nrf2). One of the 4 herbs recommended for eosinophilia (the other 3 are Albezzia lebbock, Neem, and Curcumin)
2. Binds to GABA receptors (GABAergic), reduces seizures, stabilizes EEG
3. Protects against glutamate toxicity (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351387/
4. One of the herbs recommended for schizophrenia. However, at least one study showed that Ashwagandha increases dopamine.
5. Several studies showed positive effect on cognition by increasing acetylcholine receptors.
6. as adaptogen relieves stress, depression and anxiety, also attenuates the inhibition of MAO enzymes, which may serve a beneficial role in preventing excessive MAO inhibition from other supplements, decreases testosterone
7. Low toxicity (LD50 = 7.7g/kg), heals liver by reducing liver enzymes AST and ALT. To reduce heavy metal pollutants in Ashwagandha, a root extract such as KSM-66 is preferred. Take before bed as it promotes sleep.
Bacopa Monnieri, aka Brahmi (non-specific towards Th1/Th2)
1. significantly inhibits LPS-activated TNF-α and IL-6, not clear effect on NK
2. Reduces seizures, but only in large doses
3. Inhibits glutamate dehydrogenase
4. regulates dopamine, one of the herbs recommended for schizophrenia. In a study of Bacopa for ADHD, Bacopa reduced learning problems, impulsivity, and psychiatric problems symptom scores for 78%, 67%, and 52% of children, respectively.
5. Increases cerebral blood flow, known nootrpic, reduces beta amyloid build up in Alzheimer's, one of the herbs recommended for ADHD. The efficacy of Bacopa in ADHD has been attributed to its neuroprotective and antioxidant effects, as well as regulation of dopamine, and inhibition of cholinesterase. Improves various parameters of cognition such as alertness, verbal learning, memory acquisition and recall, reaction times and depression/anxiety.
6. One study showed reduced irritability and insomnia at 300mg/2xday, reduces cortisol
7. Low toxicity (LD50 = 2.2g/kg), protects liver against toxins such as Tylenol, Morphine etc. However, it inhibits cytochrome P450 enzyme (a primary mechanism of detoxification), which can results in herb-drug interactions that can lead to liver injury. Another concern is that Bacopa monnieri is a known hyperaccumulator of Cadmium, Chromium, Lead and Mercury. So, you must request a 3rd-party Certificate of Analysis.
Honokiol/highly active polyphenol compound purified from the bark of Magnolia officinalis
1. inhibits IL-1β, TNF-α, IL-6, IL-8, MCP1 and GM-CSF, bypasses healthy cells and chokes off tumor cells, denying them the nutrients they need to survive. As effective anti-tumoral agent as common chemotherapeutic drug Adriamycin.
2. honokiol significantly increases NMDA-induced seizure thresholds by blocking NMDA-induced Ca(2+) influx
3. inhibits evoked glutamate release from glutamatergic nerve terminals of cerebral cortex, honokiol action was compared to that of Memantine. Honokiol is a positive allosteric modulator of both synaptic and extra-synaptic GABA-A receptors, which means it reduces the amount of GABA required to activate the receptor. It promotes NREM sleep.
4. can modestly inhibit dopamine transporter activity and reduce binding to dopamine (D5) and serotonin (5HT6) receptors, no influence on the other dopamine receptors (D1, D2S, D3, D4.4)
5. neuroprotective and cognition-enhancing, enhances acetycholine release thereby supporting memory
6. anti-anxiety action by activating GABA receptors, but honokiol was less likely than the diazepam to induce dependence, amnesia or depression
7. protects liver. However, Magnolia bark contains trace amounts of tubocurarine, which is an alkaloid that is commonly used as a muscle relaxant. The tubocurarine and related substances in magnolia bark may cause respiratory paralysis if it gets into blood stream. Taken orally it is very safe. LD50 oral dose for mice could not be established (more than 60g/kg). Still, to be on the safe side, it is best to buy Honokiol in an isolated form such as HonoPure (98% Honokiol)
Pycnogenol (bark extract from French Maritime pine tree)
1. significantly reduces inducible nitric oxide synthase (iNOS), which is involved in immune response, TNF-α, IL-6, IL-1β, ICAM-1 and PLIN2, increases the activity of natural killer cell
2. some users report that Pycnogenol reduced or eliminated their seizures in a stack with other anti-oxidants, but there is no published scientific evidence that Pycnogenol alone is doing anything for seizures
3. protects against glutamate induced toxicity
4. reduces dopamine by 11%
5. helps to restore cognition after TBI, was studied for ADHD and is one of the herbs recommended for that. Pycnogenol's therapeutic benefits are attributed to an increase in friendly endothelial nitric oxide (eNOS), which modulates dopamine and norepinephrine release and intake. An ancillary benefit of Pycnogenol is improvement in cerebral blood flow to regions of the brain implicated in ADHD.
6. may have a weak depressive effect possibly due to reduction in dopamine. In ADHD studies, Pycnagenol reduced excretion of catecholamines (DA, A, NA), which are typically higher in ADHD children, and increased GSH/GSSG ratio. Fatigue and irritability are possible side effects.
7. In a rat model of fatty liver (induced by a methione-choline deficient diet), 10mg/kg bodyweight Pycnogenol over a period of 5 weeks abolished the increase in serum triglycerides while attenuating the increase in liver fat and the expected increase of ALT, indicative of liver damage. After histological examination of the liver, the increase in cirrhosis and fibrosis seen in control was significantly reduced with pycnogenol. Protective effects have also been noted with rats who were experimentally diabetic, thought to be secondary to anti-oxidative effects. One study in men with erectile dysfunction noted a lowering of liver enzymes AST and y-GTP, magnitude not disclosed.
Resveratrol (Th1 booster, or perhaps non-specific)
1. Doesn't increase NK count, but activates them, reduces IL-6 and TNF-α and increases anti-inflammatory IL-10, activates Nrf2
2. Anti-convulsant and also has synergic effect with antiepileptic drugs
3. Resveratrol increases glutamate uptake (good thing), glutathione content
4. Doesn't improve symptoms of schizophrenia, but doesn't harm either
5. Doesn't improve cognition, but it acts as agonist of estrogen receptors, boosts friendly nitric oxide (eNOS), which should increase blood circulation
6. Increases S100B secretion, which is supposed to improve behaviors (S100B is the key ingredient of Russian behavioral drug Tenoten). However, Resveratrol is also a weak inhibitor of MAO-A and MAO-B, which may cause increased irritability.
7. Low toxicity, protective to liver, but it inhibits cytochrome P450 enzyme (a primary mechanism of detoxification), which can results in herb-drug interactions that can lead to liver injury
NAC (Th1 booster)
1. Significantly up-regulates NK cell activity, anti-inflammatory (reduces TNF-alpha and IL-6, promotes production of GSH, used to detox liver). However, a recent study found that lung tumors grew three times faster with NAC than without it.
2. Some anti-seizure at low doses (toxic at 75mg/kg and above, but OK at 60mg/kg and below)
3. Reduces glutamate
4. One of the key supplements for schizophrenia
5. Helps to recover cognition in traumatic brain injury, reduces OCD
6. Reduces irritability and OCD, but can cause yeast overgrowth. There is currently a clinical study underway to investigate NAC for reduction of SIB.
7. Low toxicity, actually is used to detox liver. Recommended to take in low doses (50-100mg) a few times a week. Chronic use od NAC can inhibit the body's own production of glutathione.Things that passed most of my 7 requirements:
Fish Oil (non-specific towards Th1/Th2)
Passes all 7 requirements except EPA reduces NK activity
Reishi mushroom/Ganoderma lucidum
1. Increases IL-1, IL-2, IL-6, IL-12, IFN-gamma, TNF-alpha, GM-CSF, G-CSF, and M-CSF, histamine, NK activity. May over-activate immune system, too inflammatory.
2. Known to reduce seizures
3. effect on glutamate is not clear
4. Recommended for schizophrenia
5. improves cognition
6. adaptogen, bipolar users report calmness that they couldn't get with drugs, DOES NOT inhibit MAO! It contains oils called triterpenoids which significantly reduce the production of 5-alpha-reductase - a hormone which increases testosterone production
7. Safe, used to heal liver by reducing liver enzymes. However 2 cases are reported of fulminant hepatitis (acute liver failure) after 1-2 months of taking powdered Reishi.
1. stimulates NK cell activity and boosts IFN-alpha-1, IL-2, TNF-α, and IL-6 (not anti-inflammatory), very effective immune booster, it even reverses immune suppression induced by immune suppresant drugs
2. reported anti-convulsion properties
3. protects against glutamate-induced neurotoxicity
4. effect on schizophrenia is not known
5. no strong evidence of effect on cognition
6. adaptogen, which is supposed to stabilize mood, but it also reduces MAO activity by 50%, which can lead to irritability
7. Very low toxicity (LD50 = 40g/kg), reported to be protective to liver, but contraindicated for people with kidney diseases according to kidney.org.
Vinpocetine - a synthetic derivative of the vinca alkaloid vincamine, an extract from the lesser periwinkle plant
1. reduces TNF-α, IL-1β, IL-6 and NF-κB
2. Vinpocetine is an antiseizure medication with an action similar to Carbamazepine, involving a decrease in Na(+) channels permeability. Both Vinpocetine and Carbamazepine, in addition to anti-seizure action, reduce cerebral inflammation whereas Valproic acid doesn't.
3. inhibits glutamate release through blocking of Na(+) channels, able to completely abolish neuronal injury in glutamate toxicity. Vinpocetine is also thought to be a weak and nonselective antagonist of NMDA receptors.
4. reduces intracellular dopamine by increasing the dopamine metabolite DOPAC. This increase in DOPAC and reduction of dopamine is similar to MAO activation by anti-psychotic Reserpine, but this does not appear to be the case with Vinpocetine, which appears to impair vesicular storage of dopamine.
5. Vinpocetine is Viagra for the brain. It reduces resistance in cerebral vessels, increases cerebral flow, and dramatically improves short-term memory.
6. can increase irritability if increased blood flow results in headaches. Also, Vinpocetine may temporarily deplete the monoamines serotonin, dopamine and norepinephrine by inhibiting VMAT, thus preventing them from reaching the synapse. Vinpocetine may therefore induce or exacerbate depressive symptoms as an adverse effect.
7. Low toxicity (0.8g/kg), may reduce blood pressure at high doses, reduces liver enzymes with a potency similar to Silymarin (Milk Thistle). Dose should be limited to 10mg or less.
1. Downregulates inflammatory iNOS and COX-2 gene expression, inhibits production of NO, PGE, TNF-α, IL-1beta, IL-4,5,6 and IL-8, activates Nrf2. Effect on NK cells is not clear, but Ginger is claimed 10,000 more potent than chemotherapy at killing cancer stem cells.
2. Reduces tonic-clonic seizures probably due to blockade of C(+2) channels
3. Protects against glutamate toxicity
4. Increases dopamine and libido (perhaps not good in ASD)
5. Studies show positive effect on cognition and working memory, neuroprotection in cerebral ischemia
6. Contains quercetin, which may increase irritability
7. Very low toxicity (LD50 = 250g/kg), can be used to improve liver function in lamotrigine-induced hepatotoxicity, heartburn and stomach upset are common side effects, can cause kidney inflammation at high doses
1. Decreases PGE2, TNF-alpha, IL-6, and IL-8, and increases IL-10. Not clear effect on NK cells.
2. Not clear effect on seizures
3. Reduces glutamate damage to axons
4. Not clear effect on dopamine
5. Increases blood circulation in brain, but weak effect on cognition
6. Not clear effect on behaviors
7. Low toxicity (LD50 = 20g/kg) but some internet sources warb that it may cause liver damage
Additional positive effect: promotes sweating
1. increases NK cells, significantly attenuates TNF-α, IL-1β, and IL-6
2. effect on seizures is not reported
3. protects neurons against glutamate toxicity and death through reduction in the accumulation of intracellular calcium
4. one of the herbs recommended for schizophrenia, specifically to elevate the mood, but it may precipitate an episode of mania, or violent hyperactivity, in patients with bipolar disorder
5. improves cognition thanks to inhibiting the activity of acetylcholinesterase
6. improves mood, but can overstimulate and increase agitation and anxiety, it inhibits MAO-A activity which leads to irritability in people with 'warrior gene'
7. very safe, protects liver and kidneys
Holy Basil/Ocimum sanctum
1. reduces IL-6, TNF-alpha, MIP-1alpha, and MCP-1,, potent COX-2 inhibitor
2. Rosmarinic acid found in Holy Basil reduces seizures
3. protects against MSG toxicity
4. increases dopamine and serotonin, possibly a MAO inhibitor
5. enhances cerebral circulation and improves memory, lifts mental fog. For these reasons, it has been used to treat ADD and ADHD.
6. as adoptogen protects against stress, promotes relaxation, helps to maintain normal blood sugar levels
7. promotes healthy liver functioning, eliminates harmful chemicals in the bloodstream and protects against liver disease. It also has the ability to strengthen the kidneys.
1. promotes NK cell activity, equally or more effective at reducing TNF-α and IL-6 than Resveratrol, activates Nrf2
2. no effect on seizures
3. quercetin inhibits glutamate release from cortical synaptosomes and this effect is linked to a decrease in presynaptic voltage-dependent Ca(2+) entry and to the suppression of PKC and PKA activity
4. Quercetin has potential for the treatment of neuroleptic-induced extrapyramidal side effects of schizophrenia medications. But, it inhibits MAO-A and COMT, which remove dopamine, thus increasing dopamine levels (rutin and luteolin are also MAO-A and COMT inhibitors)
5. weak effect on cognition
6. can increase irritability due to MAO-A and COMT inhibition (that is what Luteolin did to my son). It is a pity since Quercetin is another known HDAC inhibitor after Sulforphane, which should make it really good for mood stabilization and EEG normalization. There are no more known natural HDAC inhibitors.
7. somewhat protective effect on liver injury, but very high doses (>1g) may damage kidneys.
Chinese Skullcap/Scutellaria baicalensis
1. reduces NK cells and IL-2 activity (so, not really a 'Th1 booster'). In fact, one study showed that Chinese Skullcap has an anti-abortive effect by inhibiting maternal-fetal interface immunity. It also reduces pro-inflammatory cytokines TNF-alpha, IL-1beta, IL-6, IL-12. and NO. It reduces expression of COX-2, PGE2, NFkB and I-kappaB-alpha and activates Nrf2.
2. may cause sezires
3. contains Oroxylin A, which acts as Ritalin's methylphenidate in the sense that both are dopamine reuptake inhibitors. This makes Skullcap a good ADHD herb. But, Chinese Skullcap can also trigger an early on-set of schizophrenia just like methylphenidate-based ADHD drugs. Chinese Skullcap also contains baicalin, which is prolyl oligopeptidase inhibitor. Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyzes proline-containing peptides at the carboxy terminus of proline residues. It has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders. Therefore, baicalin is a highly attractive base to develop new treatments for schizophrenia, bipolar disorder, and related neuropsychiatric diseases.
4. dose-dependent inhibition of the glutamate-induced excitotoxicity through the inhibition of NMDA receptor function by interacting with the glycine binding site of the NMDA receptor. Inhibition of NMDA receptors is quite promising.
5. Improves ADHD symptoms by increasing dopamine
6. irritability ???
7. Low toxicity (LD50 = 3g/kg). Some sources claim that baicalein ingredient of Skullcap is protective to liver. But some sources claim that it may be toxic to liver. There were several reports of liver damage when Skullcap was taken together with other herbs. Biopsy proved that the damage was due to Skullcap.Things that didn't pass
Vitamin A - considered to be neurotoxic and toxic to liver, induces mitochondrial dysfunction, increases beta amyloid peptides and TNF-alpha. But, on a positive side it is one of very few substances that activate MAO-A enzyme.
Gotu Kola - inhibits the uptake of glutamate and increases GABA in the brain, but excessive doses can be slightly narcotic and can cause headache, dizziness, giddiness, or skin irritation. Harmful to liver.
Kava Kava - harmful to liver. Because of hepatoxicity, Kava Kava is banned or restricted in Germany, Switzerland, France, Canada, and Britain. MAO-B inhibitor.
Lemon Balm - causes liver damage at high doses
Goldenseal (berberine) - neurotoxic, increases sensitivity of NMDA receptors to glutamate, exacerbates neurodegeneration, causes mitochondia swelling and oxidative stress, inhibits MAO-A resulting in irritability
Gingko Biloba - can cause seizures, increases dopamine by inhibiting MAO-A/B
Ginseng (true, Panax) - can cause seizures, reduces MAO activity by 50%, which can cause irritability in 'warrior gene' carriers.
Eleuthero/Siberian Ginseng - contrary to popular belief, Siberian ginseng doesn't significantly stimulate innate macrophage immune functions, it has no effect on pro-inflammatory cytokines IL-1beta and TNF-alpha, less likely to cause seizures than true ginseng.
Cat's Claw - potent inhibitor of prostaglandin E2 production and TNF-alpha, but stimulates IL-1 and IL-6. It might cause the immune system to become more active, and this could increase the symptoms of auto-immune diseases. Cat's Claw is a MAO-B inhibitor, which may lead to irritability. Cat’s claw is rich in tannins, which could cause such gastrointestinal side effects as abdominal pain and diarrhea. Toxic to kidneys. Not recommended for a long use.
Avena sativa (Wild Oats) is also recommended as an ADHD herb, but its mechanism is based on MAO-B inhibition and dopamine increase. Wild oats are also recommended to reduce anger.
Evening Primrose - not recommended for people with seizures or schizophrenia
Maitake mushroom - increases TNF-alpha, IFN-gamma, IL-1,12, not exactly anti-inflammatory
Cocoa, Echinacea - increase IL-1, IL-6, IL-10, and TNF-α, not anti-inflammatory. Echinacea contains quercetin, which is a MAO-A inhibitor. Cocoa is also a MAO-B inhibitor, which is not good.
Garlic - different metabolites of garlic do different things, but overall it increases TNF-α and IL-6, putting it in category of pro-iflammatory
Curcumin - inhibits MAO-A activity resulting in higher neurotransmitter levels. Not suitable for people with MAO-A mutation (like my son) because it can increase irritability. It is also a sulfur based substances, which aggravate behaviors further in people with CBS mutations.
Licorice - inhibits IL-1beta, -6, and -8 and TNF-alpha, activates Nrf2, but is also a strong MAO inhibitor. Toxic to kidneys, can cause hypertension, hypokalamia, heart failure and death.
Passion Flower - can cause liver damage
Fenugreek - can cause seizures
Neem - enhance the production of IL-2, IFN-gamme, and TNF-o, not anti-inflammatory
Avoid minerals in the form of picolinate because picolinate can alter levels of various neurotransmitters