Cost effective alternatives for omega-3

[Guts]

@ 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.

Agreed, i just feel we are wasting money by trying so many things. I feel like we would be more effective if we create some sort of funds and do tests in order to pinpoint the mechanisms behind POIS All vitamins and chemicals endogenous to the body usually work the first few times, things like vitamin D, ribosine, acetyl carnitine and so forth . I believe this is due to inflammation and malabsorption.

I agree quantum,  lets just keep it at that otherwise i make this thread so personal.

Anyone interested in  plants, take a look at hydrangea species they contain stilbenoids and all kinds of coumarins which are exclusive to hydrangea macrophylla and relatives. I don't have equipment to seperate the toxins with CO2 but so far i believe those plant to be a source of multiple mast cell stabilizing compounds

[nanna1]

Thanks Muon for your feedback and suggestions. The data (test results) you provided are very useful for determining which inflammatory paths might be more or less important. 

[nanna1]

Vitamin E:
Vitamin E (alpha-tocotrienol) has the strongest neuroprotective properties of any supplement I have ever seen. It's extremely anti-inflammatory for the brain. Natural vitamin E is a mixture of 8 molecules (alpha-tocopherol, gamma-tocopherol, beta-tocopherol, delta-tocopherol, alpha-tocotrienol, gamma-Tocotrienol, beta-tocopherol, delta-tocotrienol). Most vitamin E supplements sold in stores contain alpha-tocopherol, which is the cheapest and weakest form of the vitamin. The alpha-tocotrienol form can completely inhibit glutamate and homocysteine toxicity through 12-LOX and phospholipase A₂ inhibition.
This is most important for the protecting the brain.

Inhibitory potency:
alpha-tocotrienol (Vitamin E)(COX-2, IC40 = 1 uM)(12-LOX, IC100 = 0.05 uM)(phospholipase A₂, IC50 = 0.25 uM)(iNOS, IC50 = 1.2 uM)
gamma-Tocotrienol (Vitamin E)(5-LOX, IC50 = 5 uM)(NF-kB, IC50 = 5 uM)
gamma-tocopherol (Vitamin E)(5-LOX, IC50 = 3.2 uM)
alpha-tocopherol (Vitamin E)(5-LOX, IC50 = 5 uM)

Bioavailability in humans (blood plasma concentration after 280 mg/day oral dose):
alpha-tocotrienol = 0.98 uM
gamma-tocotrienol = 0.54 uM
delta-tocotrienol = 0.09 uM
(alpha-tocotrienol) This translates into 78mg/day for phospholipase A₂ inhibition and 14mg/day for 12-LOX inhibition.

Sources:
The alpha-tocopherol form vitamin E is not as strong of an anti-inflammatory/neuroprotective as alpha-tocotrienol. Below are some good sources tocotrienols.
--Life Extension Gamma E Mixed Tocopherols & Tocotrienols 60 Softgels
Vitamin E is fat-soluble, so it may take a couple of weeks of consistent supplementation to see the full effect. In general, fat-soluble supplements are not good pre-packs. Water-solubles are are better for prepacks. Also, it may be worth considering taking vitamin E with food.

alpha-tocotrienol neuroprotection against glutamate, homocysteine and arachidonic acid at nano-molar concentrations! Wow!

Tocotrienol Data Dump:
Biological properties of tocotrienols
A list of molecular targets modulated by tocotrienols in various cell types

Ref:
Neuroprotective properties of the natural vitamin E alpha-tocotrienol.
Nanomolar vitamin E alpha-tocotrienol inhibits glutamate-induced activation of phospholipase A2 and causes neuroprotection.
Inhibition of 5-lipoxygenase by vitamin E
Studies of LDL oxidation following alpha-, gamma-, or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans.

[b_jim]

I took vitamin E since many years, it didn't reduce my Pois.

[nanna1]

I took vitamin E since many years, it didn't reduce my Pois.

Thanks for sharing your experience. There are 8 forms of natural vitamin E that are listed in the post above. If you will, could you specify which form of E you supplemented and whether it was prepack or daily? I think that information would be really beneficial to the POIS community. alpha-tocopherol is the most common form of vitamin E sold in stores and online, and it's IC50 values show that it is not an anti-inflammatory.

  Only one of the forms, alpha-tocotrienol, is shown to be neuroprotective at low concentration. The IC50 values listed for alpha-tocotrienol indicates that (in the brain) it is a stronger anti-inflammatory than of all the supplements listed in the original post.

If you can't recall the form you took, your feedback is still helpful. I may not have explained clearly the importance/distinction of the alpha-tocotrienol form in the above post on E. In any case, I will be delighted to hear from anyone about experiences with supplementing the different tocotrienol versions of vitamin E.

[b_jim]

I checked : it's the common form : dl-alpha-tocopheryl acetate.
I take it daily 5-10 mg.
As I said, I don't have any problem with inflammatory theory.
But I don't have biological proof that there is inflammatory reaction after ejaculation. My CRP is normal after ejaculation.
I never had improvment with common anti-inflammatory med (ibuprofen, paracetamol). Anti-inflammatory diet never improved my Pois except white sugar and fish.
The "fish-test" is something I recommand to Poisers.

[Quantum]

I took vitamin E since many years, it didn't reduce my Pois.

Thanks for sharing your experience. There are 8 forms of natural vitamin E that are listed in the post above. If you will, could you specify which form of E you supplemented and whether it was prepack or daily? I think that information would be really beneficial to the POIS community. alpha-tocopherol is the most common form of vitamin E sold in stores and online, and it's IC50 values show that it is not an anti-inflammatory.

  Only one of the forms, alpha-tocotrienol, is shown to be neuroprotective at low concentration. The IC50 values listed for alpha-tocotrienol indicates that (in the brain) it is a stronger anti-inflammatory than of all the supplements listed in the original post.

If you can't recall the form you took, your feedback is still helpful. I may not have explained clearly the importance/distinction of the alpha-tocotrienol form in the above post on E. In any case, I will be delighted to hear from anyone about experiences with supplementing the different tocotrienol versions of vitamin E.

Very informative post, Nanna, thanks for your precision on the exact form of vitamine E that has a high potential of being beneficial in POIS. 

Neuroprotection abilities, for me, are very interesting in POIS, since neurotoxicity through kynurenine pathways activation ( through IDO/TDO upregulation), leading to neurotoxic products, is part of my hypothesis about POIS CNS/brain symptoms, ( cognitive and emotional symptoms).

I think that the natural supplement companies in general are not there yet with alpha-tocotrienol.  Most will list only tocopherols, and some will list tocotrienol as a whole, not detailing the concentration of the four different forms.  I have found one preparation listing all 8 forms of vitamin E, and there are 5.38 mg of alpha-tocotrienol in it ( see https://www.vitacost.com/vitacost-vitamin-e-tocotrienol-complex ).

I read in another post that you have started taking alpha-tocotrienol.  Did you find a specialized supplement with mainly alpha-tocotrienol, or a complex of tocotrienols, or a Vit E complex containing alpha-tocotrienol?   Could be interesting to share the dosage of alpha-tocotrienol in the preparation you take ( and, maybe, a link to this preparation).

One of the best dietary source of alpha-tocotrienol seems to be palm oil ( https://en.wikipedia.org/wiki/Tocotrienol#Sources )

I also stumble upon a tocotrienol education site:  http://tocotrienol.org/en/  .  However, this site appears to give information on tocotrienol in general, and not specifically on alpha-tocotrienol.


P.S.   After some more search, it seems that most, if not all, tocotrienol supplements uses the proprietary complexes of the EVNol serie, from a company named ExcelVite ( http://www.excelvite.com/products/evnol-palm-tocotrienol-complex/ ).  They mainly uses palm oil as a source, and they have 6 different versions of their EVNol complex.   The informational site that I have mentioned above, http://tocotrienol.org/en/ , have been created by ExcelVite ( but they have refrained to put any commercial link on this education site and really focus on the research results, which is good - their name only appear in the "contact" section.)

[certainlypois2]

Interesting, In the past I thought palm oil might be aiding my recovery. I eat beans cooked with palm oil, i noticed when i ate a lot of the beans during the week i have my best recovery especially from cognitive symptoms. Since living by myself my palmoil consumption is pretty much at zero  and the frequency of those great recoveries have reduced.

[nanna1]

Hi b_jim,
   Thanks for sharing the vitamin E form. I didn't know there were other forms of vitamin E until I recently started looking up the IC50 values for the allergy/inflammatory pathways. It seems that natural vitamin E found in nature is always a mixture of the 8 forms. The ratios vary depending on the source. dl-alpha-tocopheryl acetate is a synthetic form of vitamin E that is not found in nature. Chemist make dl-alpha-tocopheryl acetate in bulk to sell to supplement companies because it is cheaper to make dl-alpha-tocopheryl acetate than it is to extract d-alpha-tocopherol from a plant source.

   We may be using different definitions for what constitutes an anti-inflammatory. I am defining "anti-inflammatory" as an inhibitor of an inflammatory pathway according to a quote from Preclinical Development Handbook: ADME and Biopharmaceutical Properties. 

"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

   So when I talk about anti-inflammatory, I mean a substance that has an IC50 value less than 1 uM (micromol/L). According to the below chart, ibuprofen is not anti-inflammatory according to the above definition. But the substances listed under the COX-2 inhibitor section are anti-inflammatory (but not necessarily safe).

   For paracetamol, (COX-1, IC50=113.7 uM) (COX-2, IC50=25.8 uM). So paracetamol is not anti-inflammatory either according to the above definition.
   For vitamin D3 (5-LOX, small potentiation)(COX-2, IC50 = 0.1 uM)(TNF-α, IL-6 and NF-kB, IC50< 0.1 uM). Since the COX-2 IC50 for vitamin D3 is less than 1 uM, vitamin D3 is anti-inflammatory. To put this in perspective, D3 is an 800 times stronger inhibitor of COX-2 than ibuprofen and a 250 times stronger inhibitor than paracetamol.

[nanna1]

Hi Quantum & certainlypois2,

Sources:
Below is the source of tocotrienols I bought. Gamma-tocopherol and gamma-tocotrienol also have many general health benefits.
--Life Extension Gamma E Mixed Tocopherols & Tocotrienols 60 Softgels

Also, below are some natural sources of tocotrienols from "Tocotrienols, the Vitamin E of the 21st Century: Its Potential Against Cancer and Other Chronic Diseases":


Tocotrienol Data Dump:
Biological properties of tocotrienols
A list of molecular targets modulated by tocotrienols in various cell types

[certainlypois2]

nanna1 how many of those vitamin e pills do you use in a day.

[nanna1]

certainlypois2, I'm taking two per day. One at breakfast and one at dinner.

[certainlypois2]

certainlypois2, I'm taking two per day. One at breakfast and one at dinner.

what about AGPC is it a total of 1.2g a day or 2.4 g a day.

[romies]

Very good work on Vitamin E and Vitamin D, nanna1.

My personal experience is that supplementing Vitamin E also greatly increase my libido, e.g. 2-3x the frequency in wet dreams. For just a one-time single 400IU capsule (NOT daily), the effect lingers on for 4-6 days. So Vitamin E is a catch-22 for me personally.

[nanna1]

Thanks Romies!

[nanna1]

Gallic acid (COX-2 inhibitor, mast cell stabilizer):
  half-life: 1.19 hours, bioavailability max: 1.83 uM [1],
  COX-2 IC50=0.074 uM, COX-1 IC50=1.5 uM, MCD IC50=0.5uM, NF-kB IC50=76uM [2]
Gallic acid is naturally found (to varying degrees) in green tea, dark chocolate, apple cider vinegar [3], and Triphala.

Gallic acid sources:
1. gallicum acidum liquid
2. gallic acid monohydrate liquid

Pharmacokinetics (at 50mg)

Table from: "Pharmacokinetics of Gallic Acid and Its Relative Bioavailability from Tea in Healthy Humans (S. Shahrzad, et. al., 2001)"

Plasma time points

Figure 2 from: "Pharmacokinetics of Gallic Acid and Its Relative Bioavailability from Tea in Healthy Humans (S. Shahrzad, et. al., 2001)"

Anti-viral properties:

Figure from: "Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate (Kratz, et. al., 2008)"

Figure from: "Homology Modeling of DNA polymerases of Herpesviridae family and structure-based virtual screening for inhibitor identification. (Subhashini Pandey, et. al.2015)"
Alliin and Gallic acid bind to human herpes family DNA polymerases stronger than the anti-viral Acyclovir.

1. Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans.
2. Kinetics and docking studies of a COX-2 inhibitor isolated from Terminalia bellerica fruits.
3. Gallic acid - Wikipedia

[CuriousCharacter]

Note that there is some debate about whether the average essential oil is safe for ingestion. There are some essential oil manufacturers who specifically market their products as being safe for ingestion, but these tend to sell at a much higher price point.

[swell]

I just got CLA today, nanna1 uses it.  CLA multiplies the Omega-3 benefits without some of the drawbacks of high doses of fish-oil, plus CLA is very low cost so just combining Omega-3 supplement with CLA brings the total cost substantially down.   I'm out of my POIS now, but will start using it daily since its beneficial.

[nanna1]

Note that there is some debate about whether the average essential oil is safe for ingestion. There are some essential oil manufacturers who specifically market their products as being safe for ingestion, but these tend to sell at a much higher price point.

Hi CuriousCharacter,
  Thanks for sharing. You are correct that most essential oils are not safe to ingest. The only essential oil that I know of that is safe to ingest is d-limonene (from lemon or orange oil). And orange oil can only be ingested in one or two drop doses. I think other essential oils are not safe to ingest unless there is some special carrier oil preparation.

[nanna1]

  It may be worth looking into finding a xanthine oxidase (XO) inhibitor. I wrote about XO here. There is a cascade of inflammatory events:
1. Some herpes viruses (and influenza virus, and HIV) upregulate XO to increase superoxide (O₂^-).
2. Superoxide is then used by the other oxidative enzymes (COX-2, IDO, etc...) to oxidize substrates (arachidonic acid, tryptophan, etc...)
3. This produces (PGE₂, kynurenine) and peroxide (H₂O₂)
4. H₂O₂ activates NF-kB
5. chronically elevated NF-kB causes problems
In other words, blocking the activity of XO and/or the production of superoxide will dramatically reduce the activity of all the other oxidative enzymes and NF-kB.

I just wanted to dump this info here. Chrysin, Apigenin, Luteolin were the most potent "natural" xanthine oxidase inhibitors. Allopurinol was the most potent over-all inhibitor. Lower IC₅₀ values are better, but bio-availability is always the hidden variable. (click image to see full size)

Figure from: Structure−Activity Relationship and Classification of Flavonoids as Inhibitors of Xanthine Oxidase and Superoxide Scavengers