#75

That is understandable. It is challenging to measure mood. Could also have the potential interactions etc.
I’ve tried selegiline. At around 5-10mg/day. It was ok.
If you want to stick to ITP stuff, protandim is a good option to try if you don’t like selegiline.
As I’ve tried all the protandim ingredients separately but never as the actual product.
Ashwaghanda and bacopa are probably the products that would affect mood the most.
Forskolin is also currently being tested with ITP, which raises cAMP (maybe boosting thyroid and testosterone?), and might boost dopamine or other chemicals which has some ability to boost mood.
I’ve seen some products with it mixed with various herbal extracts similar to protandim.

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#76

You’re right. +7% lifespan in males is not a lot but at least it shows it’s safe (in mice). Components are turmeric, milk thistle, bacopa, ashwagandha, and green tea. I wonder which one is the top contributor to life extension. Out of these 5, which one is best for depression? Sleep? Anxiety? Here again there’s not a lot of data about these compounds, what the optimal is, when to take them, etc.

#77

Indeed.
I saw that the ITP tested green tea extract, and curcumin (tumeric). Those did not increase life span.
So it’s either milk thistle, bacopa, or ashwagandha. Or maybe some interesting synergy with all 5 products together doing something.
From personal experience it would be ashwaghanda extract: 5% withanolides for sleep, and anxiety.
Ashwaghanda seems to have quite a few different extracts out on the market and many people seem to like/dislike various ones.
Some people say ashwaghanda worsens depression, and some say it works. So it’s very individual.
A quality product is key as many fake or under-dosed products out on the market.
Bacopa might be better for some with depression or memory issues. Or combining the 2 products.
I’ve seen people report various dosages with the different extracts.
Probably best to start low and slowly build up.

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#78

Good point. If you look at the details green tea and curcumin increased both median and max lifespan but it wasn’t statistically significant:

So it could just be that they all individually increase lifespan a bit but not enough to move the needle much unless combined.

That’s another issue with supplements. That’s why I prefer drugs. At least you’re sure of the quality. Even for omega 3 I’m considering switching to pharma-grade Vascepa (pure EPA) or Omacor (EPA + DHA) instead of whatever brand bought from Amazon with no supply chain control, potential contaminations, etc.

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#79

I remember testing my neurotransmitter levels more than a decade ago when I started to get into health optimization. Was def experimental, but might have advanced more since then. So might be with looking into.

At a glance

Neurotransmitter testing is an approach that assesses the levels of various neurotransmitters in the body, offering insights into the neurochemical balance. Common types of neurotransmitter testing include urine and blood tests, each providing distinct advantages. Urine tests, such as the Comprehensive Neurotransmitter Profile - 24 Hr by Doctor’s Data, measure the breakdown products of neurotransmitters to assess how the body synthesizes and metabolizes them. Blood tests, on the other hand, directly quantify the levels of neurotransmitters circulating in the bloodstream, offering real-time information.

These tests may play a role in assessing mental health by uncovering potential imbalances in neurotransmitter levels. For instance, mood changes may be associated with low levels of certain neurotransmitters. Selective serotonin reuptake inhibitors (SSRIs) are a class of medication often used to increase the amount of circulating serotonin. However, they may not be effective for mood changes associated with other neurotransmitter imbalances.

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#80

Haven’t read the paper (and know other papers has additional data), from the part you quoted we also have

The best responders were those with higher (aggregate) initial levels

High baseline RBC levels of EPA and DHA and a high EPA + DHA:AA ratio predict favorable depression outcomes in patients receiving omega-3 supplements.

And the best responders were those who ended up with the highest index levels

patients whose depression did not remit in the present study nevertheless increased their omega-3 RBC levels to an average of 7.2%, compared to 8% for the remitters. Further analysis of these data revealed that the probability of remission was highest in the participants in the omega-3 arm who had the highest blood levels after treatment, in the range of 9-10%, and these participants also had the highest blood levels before the trial began. This finding is similar to that reported in a review of trials of omega-3 to improve cardiovascular outcomes which concluded that the beneficial effects of omega-3 on cardiovascular outcomes in clinical trials were achieved by the patients who reached the highest blood levels of omega-3, which in many cases were higher than those typically observed in healthy controls.

So one simplified framework could also be:

  • even if higher than average levels of Omefa3 index you may want to supplement if depression

  • if you supplement, you may want to do it to above average levels

Not sure if that means that one should skip supplementing with EPA or DHA if that one is high at the outset (- based on this study)

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How much omega-3 do you need?
#81

That’s why I pay $40/year to be a member of consumerlab.com. They tested the Carlson Elite brand of EPA and it passed w/flying colors for purity, potency, lack of heavy metals, etc, and it’s the same form (and dosage) of EPA that’s in Vascepa.

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#82

Is that pure EPA? More accurate: E-EPA.

This is also ethyl esters.

#83

I don’t think this should be the framework because the papers I linked show that EPA and DHA taken individually matter as much as their sum (the so-called “omega 3 index”). So, could it be that the baseline EPA:DHA ratio determines answers to supplementation? What if someone with low EPA but normal or high DHA first rebalances EPA with EPA only supplementation and then adds DHA?

Great to know!

But I’d still prefer Vascepa. Consumer Lab does their test once, and that’s it. There can be problems in the future: supply chain issues, fraud, accident, Carlson can change their providers (contamination can come from a supplier producing the bottle, the lid, etc.), etc. On the other hand, each batch of drugs produced is tested for compliance with predetermined quality standards. No batch can be released for distribution without passing these tests. On top of that, there’s mandatory monitoring for adverse effects or quality issues.

Carlson Elite EPA contains 1.3 g of “fish oil”, including 1,000 mg of EPA as ethyl ester. Does Consumer Lab say what’s in the remaining 300 mg?

Vascepa contains 998 mg of EPA as icosapent ethyl. It also contains 30 mg maltitol (E965 ii), 83 mg sorbitol (E420 ii) and soya lecithin. Sorbitol and maltitol are sweetening agents I guess for the taste?

Yes pure EPA. Why E-EPA? Vascepa is icosapent ethyl.

Yes… so?

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#85

I was not meaning that a better framework would not take into account the subclasses

I was more saying that the data and quote you provided may not support this part of your framework:

  • Low EPA and high DHA: EPA only?
  • High EPA and low DHA: DHA only?

Perhaps the one that is low should be supplemented more, but at least the data in that post that you cited may mean or at least beg the question that/if one should not also increase the other one too

#86

My 78 yo father just did an Omega 3 test and found his level was at 4% and his Omega 6 to 3 ratio was 10:1. This is surprising as he takes 1 g of NOW Ultra Omega 3 each day and eats a lot of nuts such as walnuts.

To get him to the 8-12% range, we’re going to double the fish oil to 2 g of NOW Ultra Omega 3 and he’s going to eat more salmon.

Any other thoughts on how to improve Omega 3 levels? It seems the supplement isn’t being absorbed well???

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#87

Might be easier to figure out where all the O6 is coming from and stop it.

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#88

That could be another valid approach. Is it the ratio that is most important or the quantity. My guess is he consumes a lot of O6s so the ratio is heavily skewed.

#89

No. Here’s what is written in the OmegaQuant test:

Higher omega-3 blood levels are strongly related to improved health and longevity. Similarly, higher - not lower - blood levels of the main omega-6 fatty acid, linoleic acid, have been associated with better heart and metabolic health. AA blood levels alone are a poor predictor of health outcomes. However, there is considerable controversy regarding omega-6s in the diet and health, which is beyond the scope of this report.
Please consult with your healthcare provider before making any dietary changes. The most efficient way to lower both the Omega-6:Omega-3 and the AA:EPA ratios is to consume more omega-3 EPA and DHA from fish or supplements (see attached table). Omega-6 blood levels are less responsive to dietary changes than omega-3 blood levels. Therefore, lowering dietary omega-6s as a strategy to correct these ratios is typically less effective than raising intake of EPA and DHA. It will take 3-4 months for these ratios to reach their new levels and we recommend re-testing at that time.

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#90

Check the calculator: Omega-3 Index Calculator | OmegaQuant

He needs 2,220 mg omega 3 per day in ethyl ester form to go from 4% to 8%. But he’s already taking one capsule of NOW Ultra Omega 3 daily. Each soft gel contains 500 mg EPA + 250 mg DHA, so 750 mg omega 3. So he needs 1,470 mg more (2220-750). So 2 more capsules (1470/750). So, a total of three capsules per day. Could other brands be better? @Davin8r: how did NOW Ultra Omega 3 rank in Consumer Labs?

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#91

Thanks @adssx that’s the approach we are trying to go with. He’ll also be adding more salmon and herring to his diet to try and get the ratio back under control.

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#92

I don’t know. I think we’re missing one part of the equation and it’s probably not only the baseline EPA or DHA levels. For now, I’m sticking to EPA only as it makes me feel quite good (placebo? If so, then it’s great!). I’ll retest my omega 3 index in 3 months and adjust accordingly…

For Americans, OmegaCheck seems to be better than OmegaQuant’s Omega 3 Index. It’s more expensive, but it gives the EPA, DHA, and DPA % in RBCs whereas OmegaQuant only gives the sum of EPA + DHA in RBCs (that’s the Omega 3 Index) and if you pay more for the “Complete” test you can get the breakdown but in serum (not RBCs, less accurate). Here’s a sample report. (They’re also less conservative than OmegaQuant: for them an Omega 3 Index of 6% is optimal.)

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#93

The EPA:DHA ratio seems to matter: Heart Rate Variability and Long Chain n-3 Polyunsaturated Fatty Acids in Chronic Kidney Disease Patients on Haemodialysis: A Cross-Sectional Pilot Study 2021

Mean erythrocyte omega-3 index was not associated with HRV following adjustment for age, BMI and use of β-blocker medication. Higher ratios* of erythrocyte eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) were associated with lower 24 h vagally-mediated beat-to-beat HRV parameters. Higher plasma EPA and docosapentaenoic acid (DPAn-3) were also associated with lower sleep-time and 24 h beat-to-beat variability. In contrast, higher plasma EPA was significantly related to higher overall and longer phase components of 24 h HRV.

Healthy controls in this paper had:

  • 0.18 EPA:DHA ratio in RBC
  • 0.42 EPA:DHA ratio in plasma
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#95

Something I learned now: Ethyl esters are less bioavailable according to Rhonda Patrick:

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#96

Here’s the direct link to the guide for those who don’t want to be spammed by Rhonda Patrick: Omega-3 Supplementation Guide.pdf - Google Drive

I’m not sure the TG form is really superior to the EE form:

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What matters is reaching your EPA and DHA targets. Use the calculator: Omega-3 Index Calculator | OmegaQuant. Indeed, if you use EE, you need to take more. So what?

I asked ChatGPT what’s the best form and why pharmaceutical omega-3 products (Lovaza and Vascepa) use esters and not triglycerides:

Pharmaceutical omega-3 products use ethyl ester (EE) or icosapent ethyl (IE) forms because they:

  • Allow higher EPA/DHA concentrations.
  • Are easier and more cost-effective to manufacture.
  • Provide stability and consistency for regulatory approval.
  • Enable precise targeting of therapeutic needs.
    While triglyceride (TG) forms may be preferred for general supplementation due to superior bioavailability, the EE and IE forms are optimized for medical-grade use, focusing on delivering potent and targeted effects in patients with specific conditions.

Pharmaceutical companies spent millions in research to develop these products, if the TG form were superior, they would have chosen that.

So unless there’s data showing that one form is safer or leads to better outcomes, I think it is irrelevant.

Last but not least, I don’t think there’s pure EPA available in triglyceride form (without added vitamin E).

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