Questions & Answers
Supplements
I recommend PureLut to those sensitive to phenols. After a few weeks on PureLut, if there is no phenol intolerance (e.g. temporary hyperactivity like when eating chocolate), you can use either NeuroProtek Low Phenol (+30 mg quercetin)+1 mg rutin or regular (+70 mg quercetin + 30 mg rutin). Rutin=quercetin glycoside that is cleaved in the gut and is useful for those with GI issues.
The color used to be caramel but it has been switched to apple peel color to avoid sugars.
Yes, especially FibroProtek for allergies and CystoProtek for feline bladder issues.
It would be safe to try one softgel per 20 lb weight per day, but do not exceed four softgels/day.
Around the external genitalia area if there is vulvodynia.
Unfortunately not.
None except some transient irritability if you are phenol intolerant, and possibly some stomach irritation if you are not used to olive oil products.
None known, but polyphenols could inhibit liver metabolic enzymes.
No. That is the date of manufacture, not the expiration date.
The more you spread them out the better it would be because they active ingredients are removed from the body after about 8 hours.
It is better to take the products with food.
They should be good for at least six months best the date indicated. An expiration date is NOT mandated by the FDA for dietary supplements. The best term should be best used by that date).
No effect.
Two softgels because some is left behind and some is destroyed by the acid in the stomach.
Eurofins
Visit their website.
Every effort is made to have products shipped with ice packs during hot summer months. However, the worst that can happen is to have the softgels stick to each other, but they can get dislodged if you place the bottle in the refrigerator for 10-15 min and then shake it hard.
You're probably sensitive to phenols if you get hyper after eating chocolate or berries, but the best way is to be tested for any polymorphism mutations in the enzyme monoamine oxidase (MAO).
They can all be taken together, but there is no need to except for BrainGain that can be added in cases of brain fog.
High amounts of favonoids (polyphenols) can shut down gut bioflora and contribute to Small Intestinal Bacterial Overgrowth (SIBO).
https://pubmed.ncbi.nlm.nih.gov/23211303/
A lot depends on presence of allergies, hyperactivity, phenol intolerance, weight etcInt he absence of the above information, it is safer to start with with one softgel or its content of NeurooProtek-Low Phenol mixed in honey or hummus for one week and then advance to one twice per day if the child is about 20 kg or moreOtherwise, one dropperful of NeuroProtek-Low Phenol, twice per day in some juice or mixed with flavored cod liver oil.Depending on how low or high functioning the child is, it may take 1-3 months to see any benefit starting with improved eye contact, patience, following command and sociability. Language improvement takes longer and may require additional support such as calcium folinate depending on the levels of serum folic acid and the presence of MTHFR mutations.
The dose depends on the severity of symptoms and any comorbidities. In the absence of additional information, you should take two softgels, twice per day with some food for 3 months and depending on the benefit, you can adjust the dose.As for curcumin, grape seed extract supplements etc, they all contain phenolic compounds that are also not purified)/ The total phenolic content should not exceed about 2,000 mg/day because they can shut down gut and liver enzymes, especially in individuals who are "slow" metabolizers (mutations in the MAO, COMT and CYP3A4 enzymes)
Yes, as long as there are no open wounds in which case it should be avoided.
Yes. In fact, there may be synergistic effect because the key ingredient in the skin lotion, tetrametoxyflavone, is more potent than either luteolin and quercetin and has been shown to inhibit release of inflammatory molecules. Applying to the temples would also increase absorption in brqin blood vessels.
No. Many products may claim to have some of the active ingredients, but no products have all of them in the right combination or formulated in olive pomace oil. Please read the following publications: Theoharides TC. Luteolin supplements: All that glitters is not gold. Biofactors. 2021 Mar;47(2):242-244. doi: 10.1002/biof.1689. Epub 2020 Nov 7. PMID: 33159817.
You can be taking them as long as there is a benefit and there are no sensitivities or adverse effect.
It is best to start with one capsule per day with some food and increase to two capsules in the morning and two in the evening over a week or so. It is advisable not to exceed 4 capsules per day without asking your health provider because taking more may depend on what other supplements and medications you are taking, as well as on the activity of your liver metabolizing enzymes.
Flavonoids such as luteolin and quercetin are absorbed from the intestine less than 10% in powder form. Formulating them in olive pomace oil certified for human consumption (oleic acid content less than 1%) increases intestinal absorption 3-5 times.
The drug interactions are with the juice that can affect liver enzymes. Luteolin is from grapefruit seeds and is >98% pure, hence very unlikely it will have any interactions.However, all polyphenolic compounds can affect liver metabolism at high doses and it is recommended that the total (luteolin, quercetin, curcumin, resveratrol, bioflavonoids, soy flavonoids etc) should not exceed 1,500 mg/day.
Most likely no because luteolin is >98% pure, but it is always recommended that one starts with one capsule or its content and increase over time.
Lecithin is only in the shell so if you squeeze the content of the capsule, it is left behind. All Algonot products are switching to bovine lecithin starting this summer. Moreover, there will also be a NeuroProtek-Low Phenol liquid in dropper bottles available in May that is entirely vegan.
All new products contain bovine and not porcine gelatin.The known allergy to red meat is alpha-gal for which you can be tested.Thousands of individuals with severe sensitivities take Algonot products without an issue.However, if you have documented allergy/sensitivity to olive oil or meat you should probably avoid them. Otherwise, you can start with PureLut and use the contents of one softgel (the gelatin is in the shell only) and mix it with some honey or applesauce)-does not dissolve in water).
You can make a small hole and squeeze the content in some apple sauce, honey, or yogurt unless there is casein sensitivity. The contents do not dissolve in water, juice, or milk.
Supplements cannot have treatment claims. However, each supplement was formulated using patented combinations of natural molecules based on many years of research, clinical studies and hundreds of scientific publications.
No, but Algonot is proud to check the source, amount and purity (95-98%) using certified, independent laboratories and obtain a Certificate of Free Sale for export from the FDA.
Mast Cell
Antihistamines are not vasoconstrictive themselves, but they will prevent Vasodilation FI due to histamine, if dysautonomia is due to MCAS, then purelut will help.
https://pubmed.ncbi.nlm.nih.gov/37951572/
You may need to reach 2 sofgels, twice/day for 2-4 weeks before seeing max benefits although you may improve sooner depending on the primary symptoms and its cause. Once you tolerate PureLut at max dose, you may migrate to FibroProtek for allergy-related symptoms or to BrainGain for brain-related symptoms.
please visit
Depending on the severity and other issues, 2-4 weeks
Yes
YES-THE BEST AVAILABLE
See my list of suggestions here.
It depends. During flares or seasonal exacerbations, they must be used daily. The same is true for most MCAS and mastocytosis patients. However, antihistamines should be alternated with some drug holidays because the body gets used to them. The CYP3 enzymes should be evaluated because slow metabolizers should get less amount and possibly pulsed to avoid accumulating.
Hyperhidrosis could be related either to dysautonomia or to aggressive mastocytosis and both possibilities should be investigated further.
I would never recommend more than 2-4 mg BID tops because it is very sedating and results in lasting fatigue. Rupatadine (Rupall in Canada is a much more potent and safer antihistamine and it can also block PAF and mast cells). Canadian online pharmacies will send it with a US prescription and can also be compounded). It is also available in Latin America, EU, UK and elsewhere as Rupafin (10 mg, twice/day-you can increase to 10 mg, four times/day). See
Theoharides TC, Guerra L, Patel K. Successful Treatment of a Patient With Severe COVID-19 Using an Integrated Approach Addressing Mast Cells and Their Mediators. Int J Infect Dis. 2022 May;118:164-166. doi: 10.1016/j.ijid.2022.02.049.
Alevizos M, Karagkouni A, Vasiadi M, Sismanopoulos N, Makris M, Kalogeromitros D, Theoharides TC. Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor. Ann Allergy Asthma Immunol. 2013 Dec;111(6):542-7. doi: 10.1016/j.anai.2013.08.025.
Vasiadi M, Kalogeromitros D, Kempuraj D, Clemons A, Zhang B, Chliva C, Makris M, Wolfberg A, House M, Theoharides TC. Rupatadine inhibits proinflammatory mediator secretion from human mast cells triggered by different stimuli. Int Arch Allergy Immunol. 2010;151(1):38-45. doi: 10.1159/000232569.
Potter P, Mitha E, Barkai L, Mezei G, Santamaría E, Izquierdo I, Maurer M. Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2-11 years. Pediatr Allergy Immunol. 2016 Feb;27(1):55-61. doi: 10.1111/pai.12460.
Siebenhaar F, Förtsch A, Krause K, Weller K, Metz M, Magerl M, Martus P, Church MK, Maurer M. Rupatadine improves quality of life in mastocytosis: a randomized, double-blind, placebo-controlled trial. Allergy. 2013 Jul;68(7):949-52. doi: 10.1111/all.12159.
No, although there is some evidence it may reduce prostaglandin release from rodent mast cells.
Yes (see Miniati A, Weng Z, Zhang B, Therianou A, Vasiadi M, Nicolaidou E, Stratigos AJ, Antoniou C, Theoharides TC. Stimulated human melanocytes express and release interleukin-8, which is inhibited by luteolin: relevance to early vitiligo. Clin Exp Dermatol. 2014 Jan;39(1):54-7. doi: 10.1111/ced.12164.
Not directly (see Theoharides TC. Neuroendocrinology of mast cells: Challenges and controversies. Exp Dermatol. 2017 Sep;26(9):751-759. doi: 10.1111/exd.13288. but luteolin (e.g. PureLut) inhibits both mast cells and hyper production of thyroid hormones (hyperthyroidism). NOTE: PTH is a strong trigger of mast cells.
It is secreted from mast cells so it should be measured, but it is not specific.
Yes.
Cromolyn is tricky. In the US is a clear solution (no one knows how the company manages to do that as it is not water soluble). In Europe and elsewhere tit is available as capsules with powder that have to be swallowed with a lot of water. Less than 5% of cromolyn is absorbed from the gut , the body gets used to it very quickly (tachyphylaxis) and about 15% of patients get diarrhea. Having said that, cromolyn may help GI symptoms due to mast cells, but NOT from food because cromolyn is a weak inhibitor of histamine release from mast cells (not when histamine comes from food). In cases of food histamine, you need to recommend the supplements diamine oxidase (DAO) 15 min before meals and PureLut or NeuroProtek (1 sofgel, twice/day)-Check stool for total histamine, eosinophilic cationic protein X and calprotectin.
Definitely in anaphylaxis, almost never in urticaria unless there is unrecognized systemic mastocytosis.
No, but there is hereditary hypertryptasemia, where inactive alpha tryptase monomers are released constitutively.
Remember, you also have the diagnostic code for “mast cell activation, unspecified”. If the medical history is indicative (e.g. flushing, itching, sensitivity to heat, odors, stress), then treat it should be treated as mast cell activation-see Theoharides TC, Perlman AI, Twahir A, Kempuraj D. Mast cell activation: beyond histamine and tryptase. Expert Rev Clin Immunol. 2023;19(6):639-654. doi:10.1080/1744666X.2023.2200936
Ehlers-Danlos syndrome (EDS) belongs to a group of hereditary conditions of connective tissue, mostly evident by extreme hypermobility.
Mast cells are present in the carotid bodies, cardiac pacemakers and coronary arteries so they influence autonomic function. Mast cells are also activated by the parasympathetic system (e.g. cholinergic urticaria) and somewhat inhibited by the sympathetic nervous system. Stimulation of the coronary mast cells can mimic an acute myocardial infarction (MI) and is called “Kounis syndrome”.
Yes, it should be double-stained immunohistochemically for (a) tryptase and (b) c-kit (CD-117).
NMH (N-methylhistamine), Leukotriene E4 (LTE4), and 11beta-PGF2alpha) in 24-hour or first morning void-collected and transported cold.
It cannot distinguish, except that the NMH (N-methylhistamine) elevation would be more persistent in mast cell activation and the PGD2 metabolite (11beta-PGF2alpha) is more likely to be elevated in MCAS than in simple allergy.
All of them can be performed any time, but the closest to or during a flare may increase the likelihood of a pathologic result.
PAF is difficult to measure routinely but is involved in many allergic and inflammatory reactions. Corticosteroids block its synthesis, the histamine-1 receptor antagonist rupatadine blocks PAF receptors and the flavonoid luteolin (e.g. PureLut) block its actions.
We have published numerous times that stress, via the release of peptides such as corticotropin-releasing hormone (CRH), neurotensin (NT), substance P (SP) and others can BOTH stimulate release of pro-inflammatory molecules AND prime the mast cells to respond to allergic triggers.
COVID
If the spike protein stays around or cells make it continuously as in the adenovirus vaccine, there us a real worry about triggering or increasing the responsivity of mast cells and microglia over time. See Theoharides TC. Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome? Mol Neurobiol. 2022 Mar;59(3):1850-1861. doi: 10.1007/s12035-021-02696-0.
Hard to know, but it is a worry. See
Theoharides TC. Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome? Mol Neurobiol. 2022 Mar;59(3):1850-1861. doi: 10.1007/s12035-021-02696-0.
Tsilioni I, Theoharides TC. Recombinant SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Stimulate Release of Different Pro-Inflammatory Mediators via Activation of Distinct Receptors on Human Microglia Cells. Mol Neurobiol. 2023 Nov;60(11):6704-6714. doi: 10.1007/s12035-023-03493-7.
The consensus is NO, but it is prudent to (a) check if they are sensitive to polyethelene glycol (PEG), a preservative found in mRNA vaccines, and predicate for a few days before and a few days after one enteric-coated baby (81 mg) aspirin, an antihistamine (e.g. Zyrtec, 10 mg)and PureLut (2 softgels/day).
Yes. see
Theoharides TC. Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome? Mol Neurobiol. 2022 Mar;59(3):1850-1861. doi: 10.1007/s12035-021-02696-0.
Tsilioni I, Theoharides TC. Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33. Int J Mol Sci. 2023 May 30;24(11):9487. doi: 10.3390/ijms24119487.
Theoharides TC, Kempuraj D. Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID. Cells. 2023;12(5):688. doi:10.3390/cells12050688
Flavonoid
1. Flavonoids such as luteolin are absorbed less than 10% in powder form.
2. In order to increase the absorption of luteolin, it is mixed in olive pomace oil.
3. Gelatin is required in order to make softgel capsules containing liquid.
5. The only concern with gelatin is the presence of the antigen alpha-gal for those who are sensitive, but the company checks for that and you can be checked, as well.
6. You can avoid the gelatin by using NeuroProtek Low Phenol Liquid.
7. We are trying to make the softgels using chicken gelatin (does not have alpha-gal) or vegetarian gelatin (but so far it is somewhat unstable).
As discussed earlier, it is always prudent to start with a single agent, such as luteolin in PureLut (www.algonot.com) as 1 softgel, twice/day and slowly increase to 2 softgel, three times/day over a couple of weeks as tolerated). You should also investigate any polymorphisms in the gene coding for the enzyme COMT.
There are no available data on quercetin alone. However, two clinical trials have used NeuroProtek (contains 100 mg luteolin and 70 mg quercetin/sofgel) have been used for 4 months without issue except for transient hyperactivity if they were phenol intolerant. See Taliou A, Zintzaras E, Lykouras L, Francis K. An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders. Clin Ther. 2013 May;35(5):592-602.doi: 10.1016/j.clinthera.2013.04.006
Tsilioni I, Taliou A, Francis K, Theoharides TC. Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6. Transl Psychiatry. 2015 Sep 29;5(9): e647. doi: 10.1038/tp.2015.142.
Since then, there have been thousands of children who have used NeuroProtek and NeutroProtek-Low phenol with the longest so fat being 10 years with great benefit and no adverse effects.
No because it must be mixed during formulation to create liposomes.
Yes, especially BrainGain (2 softgel, twice/day) as tolerated plus calcium folinate (Leukovorin, 15 mg/day).
There are different preparations of luteolin either alone (PureLut or BrainGain). See Theoharides TC. Luteolin supplements: All that glitters is not gold. Biofactors. 2021 Mar;47(2):242-244. doi: 10.1002/biof.1689. or together with quercetin (FibroProtek or NeuroProtek). Luteolin in these formulations is 98% pure (tested by the third party (Eurofins) and formulated in food-grade olive pomace oil to increase oral absorption. The choice of supplement is dictated by the weight, the status of the metabolic enzymes, any sensitivity to phenols and the symptoms. It is always safer to start with a supplement with fewer ingredients (e.g. PureLut) and increase the dose over a few weeks as tolerated and then graduate to combination supplements.
Only www.algonot.com
High doses of flavonoids (>1.5 gm/day combined) inhibit the gut microbiome and disrupt the normal bioflora Function. See Duda-Chodak A. The inhibitory effect of polyphenols on human gut microbiota. J Physiol Pharmacol. 2012 Oct;63(5):497-503.
Yes, It is in liposomal form formulated in olive pomace oil alone in CystoProtek or together with luteolin in NeuroProtek and FibroProtek (www.amazon.com or www.algonot.com)
Yes, combining PureLut with GentleDerm, which contains methoxyluteolin is best. See Theoharides TC, Stewart JM, Tsilioni I. Tolerability and benefit of a tetramethoxyluteolin-containing skin lotion. Int J Immunopathol Pharmacol. 2017 Jun;30(2):146-151. doi: 10.1177/0394632017707610.
It is found in ginger, oregano and other fruits and spices in small amounts. The methoxyluteolin used in GentleDerm (www.algonot.com) is purified (98%) from citrus limon powder.
Patel AB, Theoharides TC. Methoxyluteolin Inhibits Neuropeptide-stimulated Proinflammatory Mediator Release via mTOR Activation from Human Mast Cells. J Pharmacol Exp Ther. 2017 Jun;361(3):462-471. doi: 10.1124/jpet.117.240564.
Taracanova A, Tsilioni I, Conti P, Norwitz ER, Leeman SE, Theoharides TC. Substance P and IL-33 administered together stimulate a marked secretion of IL-1β from human mast cells, inhibited by methoxyluteolin. Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9381-E9390. doi: 10.1073/pnas.1810133115.
Patel AB, Tsilioni I, Leeman SE, Theoharides TC. Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism. Proc Natl Acad Sci U S A. 2016 Nov 8;113(45): E7049-E7058. doi: 10.1073/pnas.1604992113.
Theoharides TC, Stewart JM, Tsilioni I. Tolerability and benefit of a tetramethoxyluteolin-containing skin lotion. Int J Immunopathol Pharmacol. 2017 Jun;30(2):146-151. doi: 10.1177/0394632017707610.
NO. Most soy flavonoids are estrogenic and should be avoided especially if there is any endocrine tumor in preference to luteolin, quercetin or EGCG, which have many publications showing benefit in breast cancer.
Visit the suggested approach in the relevant section. plan outlined earlier. At least, H-1 and H-2 antihistamines, plus BrainGain (2 softgels, twice/day) as tolerated plus calcium folinate (Leukovorin, 15 mg/day. If there are other skin or musculoskeletal symptoms, then add FibroProtek (1 softgel, twice/day).
For an adult with no other symptoms other than cognitive, I would recommend BrainGain (2 softgels, twice/day) as tolerated plus calcium folinate (Leukovorin, 15 mg/day. If there are other skin or musculoskeletal symptoms, then add FibroProtek (1 softgel, twice/day).
There are different preparations of luteolin either alone (PureLut or BrainGain). See Theoharides TC. Luteolin supplements: All that glitters is not gold. Biofactors. 2021 Mar;47(2):242-244. doi: 10.1002/biof.1689. or together with quercetin (FibroProtek or NeuroProtek). Luteolin in these formulations is 98% pure (tested by the third party (Eurofins) and formulated in food-grade olive pomace oil to increase oral absorption. The choice of supplement is dictated by the weight, the status of the metabolic enzymes, any sensitivity to phenols and the symptoms. It is always safer to start with a supplement with fewer ingredients (e.g. PureLut) and increase the dose over a few weeks as tolerated and then graduate to combination supplements.
The main issue is to find out WHAT they are sensitive to? Most supplements are loaded with fillers, dyes and preservatives. Luteolin in PureLut is 98% pure from grapefruit seeds. I would start by giving antihistamines and then the content of one softgel capsule to avoid the possibility of any reaction to the lecithin or the fruit coloring of the shell and then slowly increase to a whole capsule etc as tolerated. In certain cases, there may be need to prescribe methylprednisolone (Medrol 16 or 8 or 4 mg pack as tolerated) for one week and then start.
PureLut (from www.amazon.com or www.algonot.com )
Yes, especially in the formulation NeuroProtek that also contains quercetin and rutin (quercetin glycoside) that generates quercetin in the gut.
Not likely, but all flavonoids can inhibit CYP3 enzymes at doses of 2,000 mg/day or more. However, MAO and COMT break down flavonoids, so if someone is “slow metabolizer” the dose of the flavonoids will have to be adjusted down.
Supplements
I recommend PureLut to those sensitive to phenols. After a few weeks on PureLut, if there is no phenol intolerance (e.g. temporary hyperactivity like when eating chocolate), you can use either NeuroProtek Low Phenol (+30 mg quercetin)+1 mg rutin or regular (+70 mg quercetin + 30 mg rutin). Rutin=quercetin glycoside that is cleaved in the gut and is useful for those with GI issues.
The color used to be caramel but it has been switched to apple peel color to avoid sugars.
Yes, especially FibroProtek for allergies and CystoProtek for feline bladder issues.
It would be safe to try one softgel per 20 lb weight per day, but do not exceed four softgels/day.
Around the external genitalia area if there is vulvodynia.
Unfortunately not.
None except some transient irritability if you are phenol intolerant, and possibly some stomach irritation if you are not used to olive oil products.
None known, but polyphenols could inhibit liver metabolic enzymes.
No. That is the date of manufacture, not the expiration date.
The more you spread them out the better it would be because they active ingredients are removed from the body after about 8 hours.
It is better to take the products with food.
They should be good for at least six months best the date indicated. An expiration date is NOT mandated by the FDA for dietary supplements. The best term should be best used by that date).
No effect.
Two softgels because some is left behind and some is destroyed by the acid in the stomach.
Eurofins
Visit their website.
Every effort is made to have products shipped with ice packs during hot summer months. However, the worst that can happen is to have the softgels stick to each other, but they can get dislodged if you place the bottle in the refrigerator for 10-15 min and then shake it hard.
You're probably sensitive to phenols if you get hyper after eating chocolate or berries, but the best way is to be tested for any polymorphism mutations in the enzyme monoamine oxidase (MAO).
They can all be taken together, but there is no need to except for BrainGain that can be added in cases of brain fog.
High amounts of favonoids (polyphenols) can shut down gut bioflora and contribute to Small Intestinal Bacterial Overgrowth (SIBO).
https://pubmed.ncbi.nlm.nih.gov/23211303/
A lot depends on presence of allergies, hyperactivity, phenol intolerance, weight etcInt he absence of the above information, it is safer to start with with one softgel or its content of NeurooProtek-Low Phenol mixed in honey or hummus for one week and then advance to one twice per day if the child is about 20 kg or moreOtherwise, one dropperful of NeuroProtek-Low Phenol, twice per day in some juice or mixed with flavored cod liver oil.Depending on how low or high functioning the child is, it may take 1-3 months to see any benefit starting with improved eye contact, patience, following command and sociability. Language improvement takes longer and may require additional support such as calcium folinate depending on the levels of serum folic acid and the presence of MTHFR mutations.
The dose depends on the severity of symptoms and any comorbidities. In the absence of additional information, you should take two softgels, twice per day with some food for 3 months and depending on the benefit, you can adjust the dose.As for curcumin, grape seed extract supplements etc, they all contain phenolic compounds that are also not purified)/ The total phenolic content should not exceed about 2,000 mg/day because they can shut down gut and liver enzymes, especially in individuals who are "slow" metabolizers (mutations in the MAO, COMT and CYP3A4 enzymes)
Yes, as long as there are no open wounds in which case it should be avoided.
Yes. In fact, there may be synergistic effect because the key ingredient in the skin lotion, tetrametoxyflavone, is more potent than either luteolin and quercetin and has been shown to inhibit release of inflammatory molecules. Applying to the temples would also increase absorption in brqin blood vessels.
No. Many products may claim to have some of the active ingredients, but no products have all of them in the right combination or formulated in olive pomace oil. Please read the following publications: Theoharides TC. Luteolin supplements: All that glitters is not gold. Biofactors. 2021 Mar;47(2):242-244. doi: 10.1002/biof.1689. Epub 2020 Nov 7. PMID: 33159817.
You can be taking them as long as there is a benefit and there are no sensitivities or adverse effect.
It is best to start with one capsule per day with some food and increase to two capsules in the morning and two in the evening over a week or so. It is advisable not to exceed 4 capsules per day without asking your health provider because taking more may depend on what other supplements and medications you are taking, as well as on the activity of your liver metabolizing enzymes.
Flavonoids such as luteolin and quercetin are absorbed from the intestine less than 10% in powder form. Formulating them in olive pomace oil certified for human consumption (oleic acid content less than 1%) increases intestinal absorption 3-5 times.
The drug interactions are with the juice that can affect liver enzymes. Luteolin is from grapefruit seeds and is >98% pure, hence very unlikely it will have any interactions.However, all polyphenolic compounds can affect liver metabolism at high doses and it is recommended that the total (luteolin, quercetin, curcumin, resveratrol, bioflavonoids, soy flavonoids etc) should not exceed 1,500 mg/day.
Most likely no because luteolin is >98% pure, but it is always recommended that one starts with one capsule or its content and increase over time.
Lecithin is only in the shell so if you squeeze the content of the capsule, it is left behind. All Algonot products are switching to bovine lecithin starting this summer. Moreover, there will also be a NeuroProtek-Low Phenol liquid in dropper bottles available in May that is entirely vegan.
All new products contain bovine and not porcine gelatin.The known allergy to red meat is alpha-gal for which you can be tested.Thousands of individuals with severe sensitivities take Algonot products without an issue.However, if you have documented allergy/sensitivity to olive oil or meat you should probably avoid them. Otherwise, you can start with PureLut and use the contents of one softgel (the gelatin is in the shell only) and mix it with some honey or applesauce)-does not dissolve in water).
You can make a small hole and squeeze the content in some apple sauce, honey, or yogurt unless there is casein sensitivity. The contents do not dissolve in water, juice, or milk.
Supplements cannot have treatment claims. However, each supplement was formulated using patented combinations of natural molecules based on many years of research, clinical studies and hundreds of scientific publications.
No, but Algonot is proud to check the source, amount and purity (95-98%) using certified, independent laboratories and obtain a Certificate of Free Sale for export from the FDA.
Mast Cell
Antihistamines are not vasoconstrictive themselves, but they will prevent Vasodilation FI due to histamine, if dysautonomia is due to MCAS, then purelut will help.
https://pubmed.ncbi.nlm.nih.gov/37951572/
You may need to reach 2 sofgels, twice/day for 2-4 weeks before seeing max benefits although you may improve sooner depending on the primary symptoms and its cause. Once you tolerate PureLut at max dose, you may migrate to FibroProtek for allergy-related symptoms or to BrainGain for brain-related symptoms.
please visit
Depending on the severity and other issues, 2-4 weeks
Yes
YES-THE BEST AVAILABLE
See my list of suggestions here.
It depends. During flares or seasonal exacerbations, they must be used daily. The same is true for most MCAS and mastocytosis patients. However, antihistamines should be alternated with some drug holidays because the body gets used to them. The CYP3 enzymes should be evaluated because slow metabolizers should get less amount and possibly pulsed to avoid accumulating.
Hyperhidrosis could be related either to dysautonomia or to aggressive mastocytosis and both possibilities should be investigated further.
I would never recommend more than 2-4 mg BID tops because it is very sedating and results in lasting fatigue. Rupatadine (Rupall in Canada is a much more potent and safer antihistamine and it can also block PAF and mast cells). Canadian online pharmacies will send it with a US prescription and can also be compounded). It is also available in Latin America, EU, UK and elsewhere as Rupafin (10 mg, twice/day-you can increase to 10 mg, four times/day). See
Theoharides TC, Guerra L, Patel K. Successful Treatment of a Patient With Severe COVID-19 Using an Integrated Approach Addressing Mast Cells and Their Mediators. Int J Infect Dis. 2022 May;118:164-166. doi: 10.1016/j.ijid.2022.02.049.
Alevizos M, Karagkouni A, Vasiadi M, Sismanopoulos N, Makris M, Kalogeromitros D, Theoharides TC. Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor. Ann Allergy Asthma Immunol. 2013 Dec;111(6):542-7. doi: 10.1016/j.anai.2013.08.025.
Vasiadi M, Kalogeromitros D, Kempuraj D, Clemons A, Zhang B, Chliva C, Makris M, Wolfberg A, House M, Theoharides TC. Rupatadine inhibits proinflammatory mediator secretion from human mast cells triggered by different stimuli. Int Arch Allergy Immunol. 2010;151(1):38-45. doi: 10.1159/000232569.
Potter P, Mitha E, Barkai L, Mezei G, Santamaría E, Izquierdo I, Maurer M. Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2-11 years. Pediatr Allergy Immunol. 2016 Feb;27(1):55-61. doi: 10.1111/pai.12460.
Siebenhaar F, Förtsch A, Krause K, Weller K, Metz M, Magerl M, Martus P, Church MK, Maurer M. Rupatadine improves quality of life in mastocytosis: a randomized, double-blind, placebo-controlled trial. Allergy. 2013 Jul;68(7):949-52. doi: 10.1111/all.12159.
No, although there is some evidence it may reduce prostaglandin release from rodent mast cells.
Yes (see Miniati A, Weng Z, Zhang B, Therianou A, Vasiadi M, Nicolaidou E, Stratigos AJ, Antoniou C, Theoharides TC. Stimulated human melanocytes express and release interleukin-8, which is inhibited by luteolin: relevance to early vitiligo. Clin Exp Dermatol. 2014 Jan;39(1):54-7. doi: 10.1111/ced.12164.
Not directly (see Theoharides TC. Neuroendocrinology of mast cells: Challenges and controversies. Exp Dermatol. 2017 Sep;26(9):751-759. doi: 10.1111/exd.13288. but luteolin (e.g. PureLut) inhibits both mast cells and hyper production of thyroid hormones (hyperthyroidism). NOTE: PTH is a strong trigger of mast cells.
It is secreted from mast cells so it should be measured, but it is not specific.
Yes.
Cromolyn is tricky. In the US is a clear solution (no one knows how the company manages to do that as it is not water soluble). In Europe and elsewhere tit is available as capsules with powder that have to be swallowed with a lot of water. Less than 5% of cromolyn is absorbed from the gut , the body gets used to it very quickly (tachyphylaxis) and about 15% of patients get diarrhea. Having said that, cromolyn may help GI symptoms due to mast cells, but NOT from food because cromolyn is a weak inhibitor of histamine release from mast cells (not when histamine comes from food). In cases of food histamine, you need to recommend the supplements diamine oxidase (DAO) 15 min before meals and PureLut or NeuroProtek (1 sofgel, twice/day)-Check stool for total histamine, eosinophilic cationic protein X and calprotectin.
Definitely in anaphylaxis, almost never in urticaria unless there is unrecognized systemic mastocytosis.
No, but there is hereditary hypertryptasemia, where inactive alpha tryptase monomers are released constitutively.
Remember, you also have the diagnostic code for “mast cell activation, unspecified”. If the medical history is indicative (e.g. flushing, itching, sensitivity to heat, odors, stress), then treat it should be treated as mast cell activation-see Theoharides TC, Perlman AI, Twahir A, Kempuraj D. Mast cell activation: beyond histamine and tryptase. Expert Rev Clin Immunol. 2023;19(6):639-654. doi:10.1080/1744666X.2023.2200936
Ehlers-Danlos syndrome (EDS) belongs to a group of hereditary conditions of connective tissue, mostly evident by extreme hypermobility.
Mast cells are present in the carotid bodies, cardiac pacemakers and coronary arteries so they influence autonomic function. Mast cells are also activated by the parasympathetic system (e.g. cholinergic urticaria) and somewhat inhibited by the sympathetic nervous system. Stimulation of the coronary mast cells can mimic an acute myocardial infarction (MI) and is called “Kounis syndrome”.
Yes, it should be double-stained immunohistochemically for (a) tryptase and (b) c-kit (CD-117).
NMH (N-methylhistamine), Leukotriene E4 (LTE4), and 11beta-PGF2alpha) in 24-hour or first morning void-collected and transported cold.
It cannot distinguish, except that the NMH (N-methylhistamine) elevation would be more persistent in mast cell activation and the PGD2 metabolite (11beta-PGF2alpha) is more likely to be elevated in MCAS than in simple allergy.
All of them can be performed any time, but the closest to or during a flare may increase the likelihood of a pathologic result.
PAF is difficult to measure routinely but is involved in many allergic and inflammatory reactions. Corticosteroids block its synthesis, the histamine-1 receptor antagonist rupatadine blocks PAF receptors and the flavonoid luteolin (e.g. PureLut) block its actions.
We have published numerous times that stress, via the release of peptides such as corticotropin-releasing hormone (CRH), neurotensin (NT), substance P (SP) and others can BOTH stimulate release of pro-inflammatory molecules AND prime the mast cells to respond to allergic triggers.
COVID
If the spike protein stays around or cells make it continuously as in the adenovirus vaccine, there us a real worry about triggering or increasing the responsivity of mast cells and microglia over time. See Theoharides TC. Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome? Mol Neurobiol. 2022 Mar;59(3):1850-1861. doi: 10.1007/s12035-021-02696-0.
Hard to know, but it is a worry. See
Theoharides TC. Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome? Mol Neurobiol. 2022 Mar;59(3):1850-1861. doi: 10.1007/s12035-021-02696-0.
Tsilioni I, Theoharides TC. Recombinant SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Stimulate Release of Different Pro-Inflammatory Mediators via Activation of Distinct Receptors on Human Microglia Cells. Mol Neurobiol. 2023 Nov;60(11):6704-6714. doi: 10.1007/s12035-023-03493-7.
The consensus is NO, but it is prudent to (a) check if they are sensitive to polyethelene glycol (PEG), a preservative found in mRNA vaccines, and predicate for a few days before and a few days after one enteric-coated baby (81 mg) aspirin, an antihistamine (e.g. Zyrtec, 10 mg)and PureLut (2 softgels/day).
Yes. see
Theoharides TC. Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome? Mol Neurobiol. 2022 Mar;59(3):1850-1861. doi: 10.1007/s12035-021-02696-0.
Tsilioni I, Theoharides TC. Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33. Int J Mol Sci. 2023 May 30;24(11):9487. doi: 10.3390/ijms24119487.
Theoharides TC, Kempuraj D. Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID. Cells. 2023;12(5):688. doi:10.3390/cells12050688
Flavonoid
1. Flavonoids such as luteolin are absorbed less than 10% in powder form.
2. In order to increase the absorption of luteolin, it is mixed in olive pomace oil.
3. Gelatin is required in order to make softgel capsules containing liquid.
5. The only concern with gelatin is the presence of the antigen alpha-gal for those who are sensitive, but the company checks for that and you can be checked, as well.
6. You can avoid the gelatin by using NeuroProtek Low Phenol Liquid.
7. We are trying to make the softgels using chicken gelatin (does not have alpha-gal) or vegetarian gelatin (but so far it is somewhat unstable).
As discussed earlier, it is always prudent to start with a single agent, such as luteolin in PureLut (www.algonot.com) as 1 softgel, twice/day and slowly increase to 2 softgel, three times/day over a couple of weeks as tolerated). You should also investigate any polymorphisms in the gene coding for the enzyme COMT.
There are no available data on quercetin alone. However, two clinical trials have used NeuroProtek (contains 100 mg luteolin and 70 mg quercetin/sofgel) have been used for 4 months without issue except for transient hyperactivity if they were phenol intolerant. See Taliou A, Zintzaras E, Lykouras L, Francis K. An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders. Clin Ther. 2013 May;35(5):592-602.doi: 10.1016/j.clinthera.2013.04.006
Tsilioni I, Taliou A, Francis K, Theoharides TC. Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6. Transl Psychiatry. 2015 Sep 29;5(9): e647. doi: 10.1038/tp.2015.142.
Since then, there have been thousands of children who have used NeuroProtek and NeutroProtek-Low phenol with the longest so fat being 10 years with great benefit and no adverse effects.
No because it must be mixed during formulation to create liposomes.
Yes, especially BrainGain (2 softgel, twice/day) as tolerated plus calcium folinate (Leukovorin, 15 mg/day).
There are different preparations of luteolin either alone (PureLut or BrainGain). See Theoharides TC. Luteolin supplements: All that glitters is not gold. Biofactors. 2021 Mar;47(2):242-244. doi: 10.1002/biof.1689. or together with quercetin (FibroProtek or NeuroProtek). Luteolin in these formulations is 98% pure (tested by the third party (Eurofins) and formulated in food-grade olive pomace oil to increase oral absorption. The choice of supplement is dictated by the weight, the status of the metabolic enzymes, any sensitivity to phenols and the symptoms. It is always safer to start with a supplement with fewer ingredients (e.g. PureLut) and increase the dose over a few weeks as tolerated and then graduate to combination supplements.
Only www.algonot.com
High doses of flavonoids (>1.5 gm/day combined) inhibit the gut microbiome and disrupt the normal bioflora Function. See Duda-Chodak A. The inhibitory effect of polyphenols on human gut microbiota. J Physiol Pharmacol. 2012 Oct;63(5):497-503.
Yes, It is in liposomal form formulated in olive pomace oil alone in CystoProtek or together with luteolin in NeuroProtek and FibroProtek (www.amazon.com or www.algonot.com)
Yes, combining PureLut with GentleDerm, which contains methoxyluteolin is best. See Theoharides TC, Stewart JM, Tsilioni I. Tolerability and benefit of a tetramethoxyluteolin-containing skin lotion. Int J Immunopathol Pharmacol. 2017 Jun;30(2):146-151. doi: 10.1177/0394632017707610.
It is found in ginger, oregano and other fruits and spices in small amounts. The methoxyluteolin used in GentleDerm (www.algonot.com) is purified (98%) from citrus limon powder.
Patel AB, Theoharides TC. Methoxyluteolin Inhibits Neuropeptide-stimulated Proinflammatory Mediator Release via mTOR Activation from Human Mast Cells. J Pharmacol Exp Ther. 2017 Jun;361(3):462-471. doi: 10.1124/jpet.117.240564.
Taracanova A, Tsilioni I, Conti P, Norwitz ER, Leeman SE, Theoharides TC. Substance P and IL-33 administered together stimulate a marked secretion of IL-1β from human mast cells, inhibited by methoxyluteolin. Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9381-E9390. doi: 10.1073/pnas.1810133115.
Patel AB, Tsilioni I, Leeman SE, Theoharides TC. Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism. Proc Natl Acad Sci U S A. 2016 Nov 8;113(45): E7049-E7058. doi: 10.1073/pnas.1604992113.
Theoharides TC, Stewart JM, Tsilioni I. Tolerability and benefit of a tetramethoxyluteolin-containing skin lotion. Int J Immunopathol Pharmacol. 2017 Jun;30(2):146-151. doi: 10.1177/0394632017707610.
NO. Most soy flavonoids are estrogenic and should be avoided especially if there is any endocrine tumor in preference to luteolin, quercetin or EGCG, which have many publications showing benefit in breast cancer.
Visit the suggested approach in the relevant section. plan outlined earlier. At least, H-1 and H-2 antihistamines, plus BrainGain (2 softgels, twice/day) as tolerated plus calcium folinate (Leukovorin, 15 mg/day. If there are other skin or musculoskeletal symptoms, then add FibroProtek (1 softgel, twice/day).
For an adult with no other symptoms other than cognitive, I would recommend BrainGain (2 softgels, twice/day) as tolerated plus calcium folinate (Leukovorin, 15 mg/day. If there are other skin or musculoskeletal symptoms, then add FibroProtek (1 softgel, twice/day).
There are different preparations of luteolin either alone (PureLut or BrainGain). See Theoharides TC. Luteolin supplements: All that glitters is not gold. Biofactors. 2021 Mar;47(2):242-244. doi: 10.1002/biof.1689. or together with quercetin (FibroProtek or NeuroProtek). Luteolin in these formulations is 98% pure (tested by the third party (Eurofins) and formulated in food-grade olive pomace oil to increase oral absorption. The choice of supplement is dictated by the weight, the status of the metabolic enzymes, any sensitivity to phenols and the symptoms. It is always safer to start with a supplement with fewer ingredients (e.g. PureLut) and increase the dose over a few weeks as tolerated and then graduate to combination supplements.
The main issue is to find out WHAT they are sensitive to? Most supplements are loaded with fillers, dyes and preservatives. Luteolin in PureLut is 98% pure from grapefruit seeds. I would start by giving antihistamines and then the content of one softgel capsule to avoid the possibility of any reaction to the lecithin or the fruit coloring of the shell and then slowly increase to a whole capsule etc as tolerated. In certain cases, there may be need to prescribe methylprednisolone (Medrol 16 or 8 or 4 mg pack as tolerated) for one week and then start.
PureLut (from www.amazon.com or www.algonot.com )
Yes, especially in the formulation NeuroProtek that also contains quercetin and rutin (quercetin glycoside) that generates quercetin in the gut.
Not likely, but all flavonoids can inhibit CYP3 enzymes at doses of 2,000 mg/day or more. However, MAO and COMT break down flavonoids, so if someone is “slow metabolizer” the dose of the flavonoids will have to be adjusted down.
Histamine Facts
The histamine receptors are different and located in different tissues: H 1 found primarily in the eyes, mouth and skin; H 2 is located on exocrine glands; H 3 is almost exclusively in the brain and it is autoinhibitory to further histamine release. The H 4 receptor regulates the immune system, is involved in mast cell recruitment, eosinophil migration, dendritic cell activation, and T cell differentiation.
SUGGESTION: The best approach would be to inhibit the mast cells from releasing histamine and other inflammatory mediators by using PureLut or NeuroProtek or FibroProtek
Plus the anti-H1 rupatadine that also blocks mast cells and platelet activating factor (PAF) https://pubmed.ncbi.nlm.nih.gov/24267366/
Histamine in the blood is seldom elevated except in anaphylaxis and in autoimmune urticaria where histamine is also released from circulating basophils.
Histamine in the stool can be measured and reflects either a food source or release from intestinal mast cells. Giving Diamine oxidase (DAO) before meals helps only with food-derived histamine.
Histamine released outside the gut is broken down within a minute and is reflected by the presence in 24 hour urine collection (cold) of N-methyl histamine (NMH) or methyl imidazole acetic acid in cold (1-MIAA).
Histamine is the same no matter where it comes from. In HIT, there is deficiency in the enzymes [DAO=diamine oxidase and histamine N-methyltransferase (HNMT)] responsible for breaking down histamine no matter where, but most of these enzymes are found in the intestine hence we mostly associate them with foods rich in histamine.
LEGAL DISCLAIMER:
The contents of this website and any provided materials, research, or communications are for educational and informational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.
