Cost effective alternatives for omega-3

[nanna1]

Hi All,
  I noticed a while back that chewing gum could reduce my POIS symptoms by 50% or more. Originally, I thought this was from the chewing motion. But later I found out that essential oils (peppermint, spearmint, eucalyptus, thyme) are used in some gums to produce cooling, warming, tingling, spicy sensation in the mouth. Cough drops that contain menthol, camphor and thymol were also anti-inflammator in my case. The reason I bring this up is because essential oils are dirt cheap.

  Fast forward about a year, there is concern about the price of the supplements in the POIS Cascade Stack. So I have started a list of potential substitutes for omega-3 (the most expensive supplent in the stack). Below is a ranking of the anti-inflammatory potency of various supplements in units uM. The unit, uM, is short for for micro-moles per liter or uM/L. The supplements are ranked by their IC50 (50% inhibition concentration) value. Smaller values are better and mean that less is needed to inhibit the enzyme. The ranking goes from strongest (top) to weakest (bottom). The ranking assumes that arachidonic acid (AA) release is the main mediator of POIS. Therefore, the AA oxidizing enzymes and mast cell degranulation (MCD) are ranked in importance in the following way 5-LOX > COX-2 > MCD > COX-1 > 15-LOX (CYP450s are not considered). Some of the IC50 values are listed in ug/ml, but these will have to be converted to uM in order to confirm the ranking.
"In general, potent inhibitors are considered those with IC50 values less than 10 uM [159], although clinically significant interactions are expected when the IC50 values are less than 1 uM." -Preclinical Development Handbook: ADME and Biopharmaceutical Properties

• ginkgetin (5-LOX, IC50=0.33 uM)(COX-2, IC50=0.75 uM)(MCD, IC50=6.52 uM)
• Luteolin (5-LOX, IC50=2.3 uM)(COX-2, IC50<1 uM)(MCD, IC50 = 1.8 uM)(TNF-α and IL-6, IC50< 1 uM)
• omega-3 EPA (5-LOX, IC50=0.65 uM)(COX-2, IC50=1 uM)
• Thyme essential oil (name=Thymus vulgaris), (5-LOX, IC50=0.005 ug/ml)
• Tea Tree essential oil (name=Melaleuca alternifolia) (5-LOX, IC50=0.06 ug/ml)
• Oregano essential oil (name=Origanum tyftanthum, Carvacrol=42.76%, thymol=27.18%) (LOX, IC50=14.78 ug/ml)
• indomethacin (prescription medication) (5-LOX, IC50=360 uM)(COX-2, IC50=1.68 uM)(COX-1, IC50=0.028 uM)
• carvacrol (from thyme and oregano essential oil) (COX-2, IC50=0.8 uM)
• Resveratrol (5-LOX, IC50=2.7 uM)(COX-2, IC50=3.4 uM)
• Curcumin (5-LOX, IC50=0.7 uM)(COX-2, weak inhibition)(MCD, IC50 = 6.1 uM)(COX-1, IC50=50uM)
• Piceatannol (5-LOX, IC50 = 0.76 uM)(COX-2, weak inhibition)(COX-1, weak inhibition)
• Eucalyptol/1.8-cineole (IL-6, IC50=0.15 ug/ml=1 uM) (TNF-a, IC50 = 0.6 ug/ml = 4 uM)
• Cannabidiol (CBD from marijuana)(15-LOX, IC50=0.23 uM)(5-LOX, small potentiation)(COX-(1,2), weak inhibition)(IDO, IC50 = 0.9 uM)
• Boswellic acid (name=frankincense)(5-LOX, IC50 = 1.5 uM)
• Vitamin C (fat soluble) (name=Ascorbic acid 6-palmitate)(5-LOX, IC50=2.5 uM)
• Caffeic acid (5-LOX, IC50 = 46 uM)
• citrus essential oil (D-limonene>90%, orange, lemon, lime) (5-LOX, IC50=40 ug/ml)(COX-2, IC50=8.5 ug/ml)
• Chamomile extract (name=apigenin 7-O-glucoside) (COX-2, IC50=28.0 ug/mL)(aromatase, IC50=0.9 ug/ml)
• Fennel oil(name=Foeniculum vulgare) (LOX, IC50=68?2 ug/ml)
• Quercetin (5-LOX, IC50=400 ug/ml ~4 uM)(COX-2, IC50=40 uM)
• Myricetin (5-LOX, IC50 = 4.02 uM)
• Ginger essential oil (name=Z. officinale) (LOX, IC50=400 ug/ml)
• Piperine (from black pepper extract) (LOX, IC50=86 uM) (COX-2, IC50=20 uM)

I wanted to make this list "open-source". So feel free to post IC50 values for any LOX/COX inhibitors that you know of and I can update the ranking. The more supplements (IC50<10 uM)we add to the list the better. The bioavailability of each supplement varies greatly, so I know the IC50 is not a perfect representation of how effective the supplement will be for POIS. Just to be clear, I think omega-3s are essential for human life, so nothing can truly replace omega-3s in the diet. However, some supplements can serve a similar anti-inflammatory role, which is the motive for this post.

To take essential oils orally they will have to be diluted in a carrier oil like olive oil. For example, mix 1 part essential oil (thyme, oregano, or eucalyptus) with 9 parts olive oil (10% essential oil: 90% olive oil). 200mg (~0.2ml) of essential oil (2g total oil mixture) is one serving which should be taken with food since oils are fat soluble. Before you take it though, make sure you are not allergic to the oils by doing a skin allergen test. Basically, test your allergen response by applying the oil to a small area on the skin/arm and let it sit for a few hours. Initially, all essential oils cause some sort of cooling, warming, tingling, burning sensation because they stimulate the cold/pain receptors. However, they should not cause any damage or swelling (allegic response). Most of the other supplements in the list will come with some sort of intructions from the manufacturer on how to take them.

Final note, the IC50 is usually determined by incubation studies which don't determine how the inhibition happens. There are a number of ways the inhibition can occur (competitive binding, non-competitive binding, genetic expression, receptor mediated, etc...). So some of the supplements which inhibit COX/LOX by different means may be synergistic when supplemented together. It would be nice to know if there are synergies.

Graphical demonstration of the meaning of IC50.

[Hopeoneday]

Thanks Nana for this.
I yust wana warn that some people with chest muscule and odher muscule stifines, short breathing and nerve senzibility espesually severe in pois days "could maybe have bad reactions" from taking oils and suplements who are GABA antagonist (like origanao etc) etc...
For exemple in my case drinking a glas of green tee after 5 min i get relef 20 30 %.
In green tee(l teanine, grean tee can fast metabolism , increase gaba etc).

And by cheving maybe we only emprove our digestion whos most of as have bad esphsually in pois days  https://www.mindbodygreen.com/0-7775/why-chewing-your-food-can-change-your-life.html

[Muon]

I have noticed quite a few mast cell stabilizers on that list. I suspect AA metabolites play a role in POIS in particular PGD2 but not through its precursor AA but by direct release from mast cells. Hopefully I get some testing done on AA metabolites in the upcoming months. @Hopeoneday: Theanine is a mast cell stabilizer btw: https://link.springer.com/article/10.1007/s00726-011-0847-9

[b_jim]

Green tea maybe give me a small aid.

[nanna1]

Hi Muon,

   Thank you for sharing your ideas on mast cells. Below are some 50% inhibitory concentration (IC₅₀) values of (steroid/flavonoid) mast cell degranulation (MCD) inhibitors. They are ranked from strongest to weakest.

• progesterone (MCD, IC50 = 0.1 uM)
• luteolin (MCD, IC50 = 1.8 uM)
• quercetin (MCD, IC50 = 3 uM)
• fisetin (MCD, IC50 = 3.3 uM)
• curcumin (from tumeric) (MCD, IC50 = 6.1 uM)
• ginkgetin (from Ginkgo Biloba) (MCD, IC50 = 6.52 uM)
• resveratrol (MCD, IC50 = 44 uM)

   Note that clinically effective supplements have IC₅₀ values less than 1 uM. Only progesterone has a IC₅₀ value less than 1 uM. One way to test a mast cell theory of POIS is to try pregnenolone, curcumin and luteolin separately. Curcumin is a strong 5-LOX inhibitor with a LOX inhibition of IC50=0.7 uM, but a relatively weak mast cell inhibitor with a MCD inhibition of IC50=6.52 uM. Luteolin is a strong COX-2 inhibitor with a LOX inhibition of IC50<1 uM, and a modest mast cell inhibitor with a MCD inhibition of IC50=1.8 uM. If curcumin is effective at reducing your POIS symptoms then your POIS is caused by aracidonic acid (AA) release and 5-LOX interaction. If luteolin is effective at reducing your POIS symptoms then your POIS is caused by aracidonic acid (AA) release and COX-2 interaction. However, if only pregnenolone is effective, then mast cell activation may be involved in your form of POIS. Disclaimer: This is not an endorsement of pregnenolone, luteolin or curcumin.

Mast Cell Degranulation Inhibition Concentrations at 50%. Figure from "Studies of Structure Activity Relationship of Flavonoids for the Anti-allergic Actions (1998)" link below.

I was not able to find the MCD IC₅₀ values for theanine. If anyone has IC50 values (LOX, COX, MCD) for theanine, please post them.

(1)PROGESTERONE INHIBITS MAST CELL SECRETION (2006)
(2-4)Studies of Structure Activity Relationship of Flavonoids for the Anti-allergic Actions (1998)
(5)Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk. (2008)
(6)Twenty-first century mast cell stabilizers (2013)
( 7 )Inhibitory effects of resveratrol on human mast cell degranulation, cytokine, chemokine and leukotriene release (2012)

[Quantum]

Hi Nanna,

From the table you present, apigenin is a fairly good mast cells stabilizer as well.  The best way to take apigenin is from chamomile flower tops, in tea or capsules.  In bonus you get chrysin, but it seems less potent, according to that same table.  I didn't included chamomile in my pre-pack because I have it in tea, and it is not possible to prepare it in advance and keep it at bedside, but in capsules, it is cheap and could be a good add-on to a pre-pack or a daily stack, or used in tea in post-pack, when some residual POIS symptoms sets in.

Taking a combination of different natural mast cells stabilizers is a way to compensate for the fact they are less potent, alone, than prescribed ones.   In association, you get a synergy from their different modes of action, on mast cells and on other pathways too, so you act at the same time on mast cells, COX, LOX, PAF, IL-6, TNF, and so on,  and other pathways like IDO downregulation ( curcumin) and TDO downregulation ( quercetin).  I could say that this is a "broad spectrum" anti-inflammatory approach, acting on many inflammatory pathways,  by analogy to the use of broad spectrum antibiotics against the many strains of bacteria.

[nanna1]

A fresh batch of COX-(1,2) IC50 values. These are all prescription meds. For inflammation-fever-etc..., inhibiting COX-2 is most important. Only IC50 values less than 3 uM really matter, but an IC50 value less than 1 uM is ideal. As a matter of principle, I wouldn't take pharmaceutical medications. But others may have different convictions.

Disclaimer: These medication can have drug interactions. So take all the usual precautions in consultation with your healthcare physician.

[nanna1]

I should point out that this thread was started for people who find omega-3 too expensive (cost) to take in their own stack. I chose a numbers based approach (IC50 value) to compare and rank alternative anti-inflammatory supplements with omega-3 (EPA). Other metrics (i.e. IC100, EC50, etc...) are welcome as well. So far certain essential oils appear to be the best substitutes, but they have a short half-life (~30min) and must be taken around the time of orgasm or inflammation. I hope that someone can find a less-expensive longer-half-life yet effective (IC50<1 uM) anti-inflammatory that can replace omega-3.   

[nanna1]

There is a new king of the anti-inflammatory hill. I updated the first post with the following information (MCD=mast cell degranulation):

• Ginkgetin (5-LOX, IC50=0.33 uM)(COX-2, IC50=0.75 uM)(MCD, IC50=6.52 uM)
• Luteolin (5-LOX, IC50=2.3 uM)(COX-2, IC50<1 uM)(MCD, IC50 = 1.8 uM)(TNF-α and IL-6, IC50< 1 uM)
• Omega-3 EPA (5-LOX, IC50=0.65 uM)(COX-2, IC50=1 uM)

    11. Curcumin (5-LOX, IC50=0.7 uM)(COX-2, weak inhibition)(MCD, IC50 = 6.1 uM)(COX-1, IC50=50uM)

   Ginkgetin comes from ginkgo biloba. However, there are many chemicals in ginkgo other than ginkgetin. At this point, I don't know much about ginkgo and am still researching it. More specifically, it's not clear how much ginkgetin is in ginkgo. If anyone has insight on supplementing ginkgo biloba, please share.

[Quantum]

Hi Nanni,


Ginkgolides are also good PAF ( platelet activating factor ) inhibitors, PAF being another product of the phospholipase A2 ( PLA2) enzyme, which could be responsible for some of the brain symptoms of POIS ( see my earlier post on this at http://poiscenter.com/forums/index.php?topic=2505.msg21554#msg21554 ).

This inhibition effect on the platelets do make ginkgo a "blood thinning" supplement, so it is contraindicated for people on anticoagulant drugs.

I have used ginkgo in my post-pack supplementation for remaining POIS symptoms, and it is a good supplement for POIS.   I do not have memory or cognitive problem with POIS, but I suppose it could be useful for these as well, not only because of its anti-inflammatory properties, but also because it enhance the blood flow to the brain ( it has been used, among other indications, to help improve memory and cognitive capacities).

The reason why I didn't include ginkgo in my pre-pack is its positive effect on erection, related to its vasodilation properties.   As a POIS sufferer, I often avoid sexual activity or aim at controlling the frequency of release as much as possible, so facilitating erection is not always a desirable effect.

[nanna1]

Thanks Quantum for the feedback. Ginkgetin is the only thing I have found (other than steroids and asthma meds) that is a stronger inhibitor in every category than omega-3 EPA. I'll keep looking though.

[Hopeoneday]

After only one caps of ginko bilboa i got so severe atac of shortenes breath heart raicing... etc like severe panic atac.

I take this pill bilboa because of bad circulation of my extremitetes , espesualy a long apstinence time.

[nanna1]

Vitamin D3 (5-LOX, small potentiation)(COX-2, IC50 = 0.1 uM)(TNF-α, IL-6 and NF-kB, IC50< 0.1 uM)

[Muon]

I've been tested for IL-6, TNF-alpha and NF-kB multiple times all with normal outcomes. My brother did the same tests with normal results as well. I don't think these are playing a role here but then again not many POIS patients have been tested on those parameters.

[nanna1]

Hi Muon,

  Thanks for the feedback and info. I also tested negative in blood test for systemic inflammation. From what I have read, cytokines (i.e. IL-6 and TNF-alpha) only show up in the blood during an inflammatory stimulus (i.e. exercise) [Ref]. Once the stimulus has stopped, the cytokines return to normal levels. The only way to measure a rise in these proteins is to take blood samples within a few minutes of the stimulus [Ref]. I assuming this stimulus response is applicable to POIS, and one would have to take the blood test shortly after orgasm to measure the rise in cytokines. Chronic diseases, like cancer, diabetes or infection, can have elevated cytokine production. But I'm not sure POIS would fit the category of being chronic since most symptoms are associated with a stimulus (i.e. orgasm). If you took the blood tests immediately following an orgasm that caused POIS, then I may be wrong in assuming that the cytokines are produced during stimulation and orgasm.

  For others who may need background for the above discussion, cytokines such as IL-6, TNF-alpha function as signaling molecules to start the inflammatory process (i.e. upregulate COX and LOX). The first few sentences in the link Cytokines discuss this. Inflammation then continues (COX/LOX remain elevated) until another signal turns it off. Hormones, Resolvins and other (anti-inflammatory) cytokines are the "off" switches.

  Was there is another reason why you were thinking cytokines should continue to be elevated? If so, I'm sorry I didn't understanding what was being communicated in your comment.

Ref: Evidence for an exercise induced increase of TNF-α and IL-6 in marathon runners

[Muon]

I actually did test them before and after an orgasm. I also was under the assumption years ago that these particular cytokines might play a role but I'm not so sure anymore. Click on the dropbox link inside this thread and read the file 'notes' first for timestamps:
http://poiscenter.com/forums/index.php?topic=2545.0

The reason why I post these comments is because I want to prevent you from staring blind on one set of parameters which may have nothing to do with POIS. I just backed it up with some tests (not 100% proof because you will need a larger group). Perhaps you may want to think of other (inflammatory) pathways than IL-6, TNF-alpha and NF-kB related. I'm just being positive critically here.

Edit: NF-kB has been tested twice (not present in dropbox link) but not immediately after an orgasm unlike IL-6 and TNF-alpha. So NF-kB might still be involved within a very short time frame after orgasm.

[Guts]

1. Ate gingko biloba leaves, twigs , fruits and seeds because there were alot of trees growing nearby. Also took extract at high dosages for long periods of time. It reduced itching but that doesn''t imply it has anything to do with LOX or COX. Other than reduction in itching it did jack shit for other symptoms.

2. Works but you need high dosages, pharmokinetics are garbage and hard to ingest in sufficient quantities. Products on the market are dosed too low and too expensive.

3. Fish oils... took 20 grams of extract for about 3 monhts staight, did jack shit altough it helped with depression and mood. Might as well eat fish all day every day.

4. Thyme , completely nonsense because the content of compounds variates alot. Also the effects are barely noticable even at really high dosages. Only thing it does is reducing anxiety. Does jack shit for allergy symptoms.
5. Jack shit
6. jack shit, altough high dosages work wonder for anxiety or depression too expensive overall.
7. never tried this
8. jack shit
9. Works really but you need extremely high dosages and the pharmacokinetics are shit, you only absorb small amounts and the half-life is shit. tried different dosages for many weeks , usually around 600mg for one month straight. $$$$$$

10. Works however curcumin itself trigger allergic reactions. Dosages taken are 20 to 30 gram of grounded daily prepared in emulsion of lecithins, fatty acids and black pepper. Works wonders for depression and anxiety but actually triggers allergic reactions

11. Not worthwhile like resveratrol. Need high dosages and is too expensive to warrant the effects. Stilbenes are more effective than other compounds when it comes to mast cells because it does reduce itch...but then again only thing is reducing the itch when you are getting destroyed by POIS.

12. Does jack shit. Works for anxiety, breathing problems and actually reduces the negative side effects caused by cannabis. Does help inflammation but does jack shit for the most extreme symptoms of POIS.

13. CBD does jack shit , just helps anxiety but actually causes depression and myraids of symptoms
14. Triggers allergic reactions, seems to worsen everything over time just like NSAIDS.

15. Vitamin C works but you need to inject it in a special way and special solutions. Need years of experience to apply a butterfly IV, IV bag + drip, also you need to process it in a certain  way to reduce its pH. All in all will cost you shitloads of money.

16. Caffeic acid works but it might as wel been rosemaric acid or any other compound. Reduces the itch acoompanied with allergic reaction and reduced the brain fog. Amounts of rosemary used where very high amounts.. high enough to make you cringe for the rest of the day.

17. Tried essential oils.... none of them worked except pinus pinaster oil ( oral ), lemongrass, nutmeg and calamus. Even then the improvement minor, nutmeg is by far the most effective mast cell stabilizer / inhibitor but is also a aphrodisiac and makes you high, also toxic to liver etc.

18. chamomille works against itch and does it well but does little for other symptoms.
19. does jack shit

20. Quercetin works but is too expensive. Amounts you need for a significant reduction in symptoms cause all kinds of side effects just like caffeine including insomnia, stimulation etc etc . not worth the money because again the pharmacokinetics are garbage. Amounts i needed were at least 1 gram of quercetin 3 or 4 times a day and the same amount of rutin.

21. works somewhat, expect to get fucked up by POIS anyway.
22. Ginger .. worst thing i can take
23. doesn't do anything

i've been using cannabis for years now and have been growing CBD rich strains for almost 8 years. Strains are CBD nordle, CBD med gom, Fast eddie, Amnesia auto CBD. Also THC rich strains like white widow, northern lights and many others. Right now i vape 4 grams to 6 grams each day and it does jack shit besides helping me sleep and for anxiety. Even cannabis itself triggers allergic reactions in me now and then. I've also been taking niacin for many years and it actually made everything worse long term, i believe i would have been better off without it.

Most natural compound are eliminated too fast from the body and barely get absorbed. POIS patients already have GI problems and malabsorption so anything besides the injection route will probably be useless. Even then the Half-Life is garbage. I'm not saying you shouldn't try new things but one that doesn't hold a job won't get any worthwhile effects from these expensive supplements. I personally don't even take these threads seriously anymore, i've been isolating compounds for many years and tried them and rarely had any success.

Also the TNF-A model and IL-6 model is severely outdated and rarely is implicated in rarer diseases. Like muon said i've also tested for TNF-A and IL-6 and the results were normal. Everything i read on pubmed did jack shit and everything i read on these forums did jack shit. Only thing that helped is alpha lipoic acid but that's because of my pre-diabetes and has little do with POIS itself. Studies revolve around TNF-a and IL-6 because it's implicated in diabetes and researchers want a big piece of that money industry that's called diabetes so they model their studies after it.

Question is am i better of then previous years with all that cannabis use, supplement and herb use and medicine use.... No i maybe even got worse because of some supplements triggering reactions.  It also made me jaded and made me reject this forum and became very biased towards these idiot researchers setting people in wrong directions.

Also alot of people actually mast cell activation from NSAIDs , LOX or PGE inhibitors this also has been my experience. People don't read the shit that muon for example wrote , people are hang up about taking garlic and niacin and all this other shit because it gives them a feeling they can control the symptoms in which the end is just another delusion.

[Guts]

o yeah and theanine i have been taking for years.

lately i've picked it up again for lower prices and took higher dosages like 2 grams and 5 grams. reduces anxiety and what have you but actually triggered mast cell activation. My whole face and back was itching all nights.

[Muon]

@ Guts: You don't know if those reactions from supplements are related to mast cell activation, it's a guess. Bottom line is that more patients need to be tested for obscure/non-standard parameters before we can jump to conclusions.

Other thing is POIS might be caused by different mechanisms and supplement A could work for person X but not for Y, be careful not to discard positive experiences people have with specific supplements (even if these don't work for you and me). Many supplements can trigger allergic-like symptoms in me as well.

Second thing, the problem with supplement related papers is that they have been mostly tested via in vitro experiments. You rarely see any in vivo studies.

[Quantum]

o yeah and theanine i have been taking for years.

lately i've picked it up again for lower prices and took higher dosages like 2 grams and 5 grams. reduces anxiety and what have you but actually triggered mast cell activation. My whole face and back was itching all nights.

Hi Guts,

In this post, and in your previous post where you list many dosage you took in the past, you mention higher dosage, if not excessive dosage, and then mention side effects.  It is quite normal to get adverse reactions from high or excessive dosage, as many adverse effects are dose-dependant.

My approach has been to use multiple supplements at low dose, and it has yield very good results, if you have the patience to develop your stack over 3 to 6 months.  All in all, it's better to take that slow but safe approach, than go on with years of POIS.

Through your other, longer post you express a huge amount of anger and frustration against POIS, but please, do not project those negative feelings toward this forum and toward its members - they are not the cause of your POIS.  Also, try using less reference to your friend jack ( I am sure you can convey your opinion without constant reference to fecal matter as a way to put emphasis).   We are all affected by the same syndrome that you have.   You could have shared your opinion about those various supplements,which is valuable information, but without the venting aspect, and it would have been more interesting to read. 

For now, nobody has anything clear and established to say about POIS, so be patient, and respect all opinions.  We want this forum to be a safe place for any member to express his thought about POIS, so if you have problem with a hypothesis express on the forum, you can for sure comment on it, but in a polite and respectful way.

Take good care of yourself, Guts, and I truly wish you to find some relief both with your POIS and with your emotional struggle caused by it.  POIS is really heavy on the negative side, and I can say that my 10 years ( and still going on) of psychotherapy have been really a life saver for me, and I do not hesitate to recommend to any POIS sufferer to find a really competent psychologist, who manifest compassion and is intelligent.   It does not heal POIS, but it can heal the trauma of having POIS, and after a few years, things get a little easier to bear.  On the long term, after 5 to 7 years, your life has significantly change for the better ( that is my experience, anyway, because I have found an excellent psychotherapist, who was not afraid of the "severe case" that I was , which was not only limited to me having POIS ).  I must admit that psychotherapy is not cheap, and that I am grateful for having had the money to do so, and I wish anybody could have access to this essential service  ( usually, through the medical system, we only have access to psychiatrists, but they are doctors and only have time to prescribe drugs, essentially - no time to engage in a real therapy, and seeing you for 45 mins to 1 hour every week, develop a deep bond and have time to really be with you and care - psychotherapist/psychologist are more appropriate for this).