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  #31  
Old 11-19-19, 10:15 PM
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Re: I'm Sure There Must Be Hormones Involved (Might Not Be the Ones You Think)

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So I wonder what is the neurochemistry of food cravings, anyway?
Unfortunately I think most of this "listen to your body" advice has no scientific credibility, but here is an amusing chart of what your body is supposedly trying to tell you by whispering "chocolate" and "donuts" to your vagus nerve and trying to get it to agitate your brain to send out for room service. Honestly I think your gut bacteria probably have more to do with unhealthy cravings. Still, the fish craving is curious, isn't it?


In my case I have clear laboratory evidence that any craving for salt in pickled herring is NOT due to a genuine need for Chloride, as I am borderline hyperchloremic, which I am trying to bring down with small daily bites of sodium or potassium bicarbonate (luckily I don't have to worry about either Na or K, and bicarbonate should release and replace the excess chloride I seem to be hanging onto...next labs will tell if I am right about this)
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Old 11-19-19, 10:20 PM
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Re: Head's Up on Long-term High-dose Omega-3's

Are you aware of the work of Dr Patrick Nemechek on dysautonomia (specially focussing on autism?).
One of his areas of interest is microglial inflammation.
He is looking at a regimen focussing on vagus nerve infammation, omega 3s and olive oil (a fat alternative that is not high in omega 6).
His work is summed up here, and he has good short books on his commercial site.
My take on this is that I would like to see more confirmation, but the basic physiology is sound.


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  #33  
Old 11-19-19, 10:56 PM
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Re: Head's Up on Long-term High-dose Omega-3's

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Originally Posted by Kunga Dorji View Post
Are you aware of the work of Dr Patrick Nemechek on dysautonomia (specially focussing on autism?).
One of his areas of interest is microglial inflammation.
He is looking at a regimen focussing on vagus nerve infammation, omega 3s and olive oil (a fat alternative that is not high in omega 6).
His work is summed up here, and he has good short books on his commercial site.
My take on this is that I would like to see more confirmation, but the basic physiology is sound....
That is interesting, and may resonate with a general notion I have that our modern life and culture tends to continuously overactivate the sympathetic nervous system, while understimulating and undersupporting the parasympathetic system.

The 2 most basic balancing strategies I've come up with are 1)getting more sleep and rest intermittently with getting adequate exercise, and 2) fasting--or at least not snacking-- intermittently with eating well. But others such as walking outdoors, early morning sunlight, deep breathing, meditation, yoga and socializing may all tend to support better parasympathetic tone.

And I would love to understand more about the vagus nerve and heart rate variability. Not having access to a vagus stimulating device, I have attempted to improvise my own vagus nerve stimulation through singing, long exhalations and occasional Valsalva maneuvers, but I have no way of assessing the effect. Just a hunch, really.

And microglial activation is something that has just come onto my radar, too recently for me to have much idea about it. Interesting to think that the olive oil, Omega-3's and curcumin I already take might be helping....
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Old 11-20-19, 01:13 AM
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Re: Head's Up on Long-term High-dose Omega-3's

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That is interesting, and may resonate with a general notion I have that our modern life and culture tends to continuously overactivate the sympathetic nervous system, while understimulating and undersupporting the parasympathetic system.

The 2 most basic balancing strategies I've come up with are 1)getting more sleep and rest intermittently with getting adequate exercise, and 2) fasting--or at least not snacking-- intermittently with eating well. But others such as walking outdoors, early morning sunlight, deep breathing, meditation, yoga and socializing may all tend to support better parasympathetic tone.

And I would love to understand more about the vagus nerve and heart rate variability. Not having access to a vagus stimulating device, I have attempted to improvise my own vagus nerve stimulation through singing, long exhalations and occasional Valsalva maneuvers, but I have no way of assessing the effect. Just a hunch, really.
Sticking your head in a bucket of Ice water works well for vagal tone for about the next 30 minutes.

Re sympathetic tone: Ive had a breakthrough there.
It relates to the neck- which was still tight on the back right- and I had an abnormally strong R sided sympathetic response.

I finally got the neck to behave (the problem was lack of movement on the R side- leading to a cascade up to the right cortex, leading to a descending lack of activity passing through the pontomedullary reticular formation and a failure of suppression of the right intermediolateral column in the spinal cord.

The IML is a column of 'always on' cells in the sympathetic nervous system that suppresses the parasympathetics and relies on suppression from the same side PMRF.

This is a huge shift, and I immediately (well withing 10 minutes) found the sympathetic tone dropped and my fingers warmed up.
Im sure this is of wider importance.

Its explained in better detail here:
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  #35  
Old 12-16-19, 05:18 PM
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Strikingly Different Functions of EPA and DHA

I came across this older article from 2012 which offers a readable description of how the 2 marine Omega-3's, EPA and DHA, are different molecules with completely different characteristics and functions, both in the brain and in the peripheral circulation.

https://www.psychologytoday.com/ca/b...en-epa-and-dha

Although there is nothing in the article about the risks to getting too much of either, we can probably gather that the risks of oversupplementation--when they are reported-- will be completely different for EPA than DHA. Despite the fact that there is some convertibility amongst the Omega-3's, one might even guess that a person could continue to be deficient in one whilst becoming oversaturated in another (particularly DHA, as it is the endpoint of the conversions with supposedly the longest half-life?).

One interesting point in the article is that DHA inhibits (article says "inhibits" but I think it might mean "competes for") an enzyme that helps convert an important Omega-6, GLA, into important metabolites. To get around this, it suggests that you might have to further supplement with DGLA:
it also has the more immediate effect of reducing the production of the next metabolite known as dihomo gamma linolenic acid or DGLA. This can be a disaster as a great number of powerful anti-inflammatory eicosanoids are derived from DGLA. This is why if you use high-dose DHA it is essential to add back trace amounts of GLA to maintain sufficient levels of DGLA to continue to produce anti-inflammatory eicosanoids.
Unfortunately there is no citation of the research on this point, so I will have to do some Google-fu to track it down.
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  #36  
Old 12-16-19, 05:21 PM
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Impulsivity--First Signs of a Downside to Excess EPA?

I just posted in another thread a very interesting study to come out of Taiwan. Children diagnosed with ADHD were given "high" doses of 1.2g EPA per day (not really very high, compared with other studies testing ADHD and MDD in adults using 3-5 grams combined fish oil per day) for 10 weeks. In this case, however, the children were tested at baseline for EPA concentrations in their blood, and this turned out to predict very different outcomes.

The children with low baseline EPA showed improvements in "attention" and "vigilance" even greater than with MPH medication. However the children with median to high baseline EPA not only did not improve, they also showed increased "impulsivity."
Previous studies have found inconsistent findings of omega-3 supplementation on ADHD symptoms, with overall effect sizes being relatively small. Standard treatments offered to parents whose children have ADHD include stimulants such as methylphenidate. The effect size of improvement in attention and vigilance from methylphenidate is 0.22-0.42. In comparison, the effect sizes in the trial of omega-3 supplementation for those children with low blood-levels of EPA were larger, at 0.89 for focused attention and 0.83 for vigilance.
It was also noted that fish consumption being relatively high in Taiwan, EPA levels in children elsewhere were likely to be lower than in this sample.

Omega-3 fish oil as effective for attention as ADHD drugs for some children,
https://medicalxpress.com/news/2019-...attention.html

Here is the original article: https://www.nature.com/articles/s41398-019-0633-0

Keep in mind we can guess that the reason some children had "naturally" high levels of EPA was that they ate more fish, or that the reason for their increased impulsivity was excessive EPA, but those aren't the only possibilities. The important takeaways from this study (and their previous one) are that those with ADHD who also have low levels of EPA are a) more likely to have more severe ADHD, and b) can show more improvement in attention from taking EPA than methylphenidate. (This is not to say they might benefit even more from taking both.)

I think this work also opens up 2 more important possibilities about Omega-3's, that goes beyond ADHD to other supposed benefits. The first is that any observational studies on Omega-3's should probably test for baseline levels first, as this is very likely to be a confounding factor in all subsequent results. And why wouldn't it be? Even if functional deficiencies are rampant in a modern urban diet, if you are not even slightly deficient, why would adding more be of benefit? There could be many reasons why the beneficial effects of Omega-3's will be greater in some people than others, but without baseline testing we have no basis for further questioning.

The second, following on my earlier post about the U-shaped curve found for one of the Alzheimer's processes in vitro, is that we may be starting to see more signs of a U-shaped curve for Omega-3's in human functioning. A "U-shaped curve" is similar to the Goldilocks principle: too little is bad, too much is also bad, but somewhere in the middle is just right.

To be honest, this is what I would expect to see with almost any substance that competes with other substances for enzymes and pathways, even more so if it is oil-based, so that any excess is less likely to be dissolved in water and excreted more or less immediately. I'm surprised it has taken this long to show up, and I expect to see more in the future.

Last edited by 20thcenturyfox; 12-16-19 at 05:35 PM..
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  #37  
Old 12-16-19, 05:24 PM
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Omega-3's and Depression: A Few More Hints of Dangers of Excess Supplementation

Long before I knew I had ADHD, I was aware of studies that supported Omega-3 fish oil for depression. Although many of the studies used doses of 4-5g per day, for a long time I only took around 2 g/day, along with antidepressants. I did have the impression it was helpful for concentration, which was my main depression complaint (maybe why my doc suspected ADHD before I did).

About 2 years ago, long after I had discontinued antidepressants, I had a depressive relapse, and started reviewing the literature again. Since the doses used in the studies were much higher than I was taking, I bumped up my Omega-3 supps to 4-5g/day. I have improved a lot (no telling which interventions are responsible), but I began having 2nd thoughts about continuous high doses of something oily, so that was the inspiration for this thread.

Now from China is a new review attempting to tease out the effects of EPA and DHA at different doses on depression. They did not find enough specifically on DHA alone to draw any conclusions, but they concluded there is good evidence of EPA improving depression at doses around 1g/day. They found there was no substantial evidence of more improvement at higher doses.

In the discussion were 2 interesting hints of possible problems with higher (how high? )doses of EPA. First was a speculation that EPA would only be helpful in those cases of MDD where neuroinflammatory markers were part of the pathology, and might even be harmful in cases where other processes were involved. (Rappoport, 2015, could not get full text, https://www.nature.com/articles/mp201522 )

The other was a study (uncited?) that excess EPA could interfere with the metabolism of SSRI anti-depressants:
Second, a study demonstrated that EPA at high dosages may hamper the activity of CYP2D6 and CYP2A4, which are considered major enzymes in the metabolism of antidepressant drugs (selective serotonin reuptake inhibitors, SSRIs).
Here's the review article: Efficacy of omega-3 PUFAs in depression: A meta-analysis, 2019, Liao et al https://www.nature.com/articles/s413...or-information
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Old 12-17-19, 01:10 PM
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Re: Impulsivity--First Signs of a Downside to Excess EPA?

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I just posted in another thread a very interesting study to come out of Taiwan. Children diagnosed with ADHD were given "high" doses of 1.2g EPA per day (not really very high, compared with other studies testing ADHD and MDD in adults using 3-5 grams combined fish oil per day) for 10 weeks. In this case, however, the children were tested at baseline for EPA concentrations in their blood, and this turned out to predict very different outcomes.

The children with low baseline EPA showed improvements in "attention" and "vigilance" even greater than with MPH medication. However the children with median to high baseline EPA not only did not improve, they also showed increased "impulsivity."
I don't know whether the above study is the first to report increased impulsivity as partial outcome of EPA supplementation, but unknown to me, there is actually a line of studies where Omega-3's have been used to reduce impulsivity and aggression in humans.

In another very comprehensive Italian review from 2012 the authors looked at all qualifying studies of the effects of Omega-3s in a wide range of psychiatric disorders, including ADHD and MDD, but also including aggression and impulsivity.
In the last two decades, growing attention has been given to the potential role of omega-3 in clinical conditions characterized by high impulsivity, hostility and aggressive behaviors [5]. The discovery of low levels of EPA and DHA in the central nervous system of patients with impulsive-aggressive, self-harm and parasuicidal behaviors [111,112] has encouraged the investigators to perform trials on omega-3 implementation in this clinical population characterized by a high level of impulsivity and aggression with favorable results in terms of mood symptoms and control of impulsivity [113,114]. Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data, 2016 Bozzatello et al, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999787/
What is most striking from that time is that, while efficacy ranged from inconclusive to dramatically positive, there was a remarkable lack of negative outcomes and adverse events.

This is best illustrated in a short section entitled "Adverse Effects" covering only bleeding risk, glucose control, and cardiovascular risk--nothing about possible neurological or other risks of oversupplementation:
Omega-3 fatty acids did not induce serious adverse effects and were generally well tolerated: most common side effects reported in clinical trials were nausea and a fishy aftertaste, but they were mild and rarely induced discontinuation [125]. The Panel of The European Food Safety Authority (EFSA) concluded that the available data are insufficient to establish a tolerable daily intake (UL) of DHA, EPA and DPA individually or in combination, but the supplementation with EPA and DHA up to 5 g/day is not dangerous for the general population [126]. In particular, EPA and DHA are generally recognized as safe and well tolerated at dose up to 5 g/day in terms of bleeding risk, as pointed out by Yokoyama et al. [127] and Tanaka et al. [128]. In addition, doses up to 5 g/day, consumed for a maximum period of 12–16 weeks, do not significantly affect glucose regulation in both healthy and diabetic subjects [119,129,130,131] and do not increase infection risk by the activation of inappropriate inflammatory responses [132]. The intake of EPA and DHA at the same dose and up to 16 weeks does not induce alteration of lipid peroxidation and does not increase cardiovascular risk [133]. Combined intake of EPA and DHA at the dose of 2–6 g/day and intake of DHA at the dose of 2–4 g/die are responsible for an LDL concentration increase (3%), but do not affect cardiovascular risk. At last, an intake of EPA at the maximum dose of 4 g/day does not induce significant changes in LDL plasma levels [134].
Of course it is still early days. But what the Taiwan research may be signalling is that, even if Omega-3 deficiencies are widespread in modern conditions, and even if such deficiencies are disproportionately prevalent/severe in psychiatric populations, the benefits of supplementation are likely to be limited to correcting the deficiency. Those with naturally (or already supplemented) high levels of plasma EPA are less likely to benefit from additional supplementation, and more likely to suffer some yet-to-be-identified consequences of excess Omega-3's.

Is this surprising? No. What is most surprising to me is that in 30 years of research and experimentation, no serious effects of oversupplementation have so far been identified. This must make Omega-3's the closest thing to snake oil, since Vitamin C!
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Old 12-17-19, 02:33 PM
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Re: Head's Up on Long-term High-dose Omega-3's

The only problem other than fishy burps I've ever read about was increased
risk of bleeding. I've been having purpura (spots of bleeding that look purple
just under the skin) on my arms for about 3 years. My PCP said it thin skin
from aging, but I cut back on my Omega 3, from 2000 units to 1000 units per
day. Hasn't made any difference with the purpura, but hasn't has a negative
impact on my focus either.
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Old 12-17-19, 10:26 PM
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Re: Impulsivity--First Signs of a Downside to Excess EPA?

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Is this surprising? No. What is most surprising to me is that in 30 years of research and experimentation, no serious effects of oversupplementation have so far been identified. This must make Omega-3's the closest thing to snake oil, since Vitamin C!
Interestingly, though not widely taken up yet, it looks like the role of high dose Vit C in overwhelming sepsis is valid.
These infections draw down Vit C supplies- creating a sort of acute scurvy, with soft tissue fragility and clotting in and bleeding from blood vessels.
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