Low Toxin Diet Grant Genereux's Theory Of Vitamin A Toxicity

[zarrin77]

There are probably hundreds of publications talking about this supposed deficiency, and how mothers or infants need to be supplemented with DHA to prevent it. Most preterm infants are characterized as deficient since the small amount that is present in a newborn's brain is only incorporated into the brain during the end of the last trimester. It's a well known fact that, at birth, DHA concentration is very low, or deficient if you want, and then rapidly accrues during the first two years of life.

DHA Effects in Brain Development and Function

My question was: Please provide a source that babies are born “deficient in EPA / DHA”.

The source you gave says: “Its [DHA] accumulation in the fetal brain takes place mainly during the last trimester of pregnancy”.

Thus, babies are not born “deficient in DHA”.

And if you look at the plethora of data out there in both rodents and humans, having little to no omega 3 in the diet impairs fetal brain development, it never promotes it.

 

[zarrin77]

Not exactly what you are requesting, but close. I think Peat thinks that Mead Acid (produced endogenously during an EFA deficiency) can fulfill any requirements the body has for PUFA.

Abstract
To determine the incidence of essential fatty acid (EFA) deficiency during short term fat-free parenteral nutrition, the authors investigated prospectively the EFA status of nine low birthweight (1145 +/- 343 g) preterm (28.2 +/- 1.9 weeks) infants, in whom delivery of dietary fat was delayed postnatally for 2-9 days. Serial determinations of plasma fatty acids showed that during fat-free alimentation, the major EFA, linoleic acid (LA), decreased rapidly (-0.75% total fatty acids per day), accompanied by a rise in endogenously produced non-essential fatty acid, eicosatrienoic acid (Mead acid). Essential fatty acid deficiency was confirmed biochemically by an elevation in the triene-tetraene ratio in six of the infants, only one of whom developed clinical symptoms. Abnormal fatty acid profiles were corrected within a few days of fat delivery by either intravenous or enteral routes. Essential fatty acids and their metabolites are involved in a wide range of physiological functions vital to postnatal growth and development. Depletion of these nutrients can be corrected by providing a minimum of 0.25 g LA/kg per day (equivalent to 0.50 g/kg per day of 20% intralipid or 30-50 mL/kg per day of breast milk).
Essential fatty acid deficiency in parenterally fed preterm infants - PubMed

A fat free diet will always produce EFA deficiency. This study is nothing new. Babies shouldn’t be fed a fat-free diet, they should be getting breast milk.

 

[zarrin77]

For anyone reading the forum looking for health advice, read Ray's articles on his website and subscribe to his bi-monthly newsletter (all of which are fully cited). Here are some articles to get you started:

Unsaturated fatty acids: Nutritionally essential, or toxic?

The Great Fish Oil Experiment

Unsaturated Vegetable Oils: Toxic

I’ve gone through his references on his website with fish oil. The vast majority were rats using diets of 10-20% of calories as fish oil (the human equivalant of 30-60 GRAMS of fish oil a day). One of the studies injected fish oil in large amounts directly into the brain...

This is not the same as getting 1-3 grams of fish oil a day from either fresh fish or a respectable brand of fish oil (in the early 200’s most of the fish oils in the market were already rancid by the time you bought them, and thus didn’t get good results.)

 

[Tarmander]

I’ve gone through his references on his website with fish oil. The vast majority were rats using diets of 10-20% of calories as fish oil (the human equivalant of 30-60 GRAMS of fish oil a day). One of the studies injected fish oil in large amounts directly into the brain...

This is not the same as getting 1-3 grams of fish oil a day from either fresh fish or a respectable brand of fish oil (in the early 200’s most of the fish oils in the market were already rancid by the time you bought them, and thus didn’t get good results.)

to be fair, some of those studies he references are at the microbiology/petri dish level and are very convincing. I know alot of people poo poo those types of studies as not translating well to human experiences...buuutt when you see T cells and other immune markers being suppressed really hard, and then immune suppression is on of the symptoms of high fish oil intake...Ray has a point

 

[zarrin77]

to be fair, some of those studies he references are at the microbiology/petri dish level and are very convincing. I know alot of people poo poo those types of studies as not translating well to human experiences...buuutt when you see T cells and other immune markers being suppressed really hard, and then immune suppression is on of the symptoms of high fish oil intake...Ray has a point

I disagree. It is well kown that what plays out in-vitro doesn‘t necessarily occur in vivo, and much less, in humans. Many of the in-vitro studies used very large doses as well.

We cannot say that becuase something has a negative effect at very high (essentially non-physiological doses: How could you get 30-60 g of fish oil a day naturally?), that it is “bad” and should be avoided.

1-3g of fish oil a day has repeatedly shown beneficial effects in the highest quality of evidence: Human RCTs.

More food for thought: Mead acid has 3 double bonds, same as the omega 3 fatty acid ALA. Thus, it is JUST as susceptible to oxidation as ALA. Yet, administering ALA has shown neuroprotective effects again and again. This is likely partly becuase ALA (and the other omega 3s) can get non-enzymatically oxidized to *anti-inflammatory* oxylipins, which appears to benefits the body in low amounts.

The prostaglandins produced from EPA / DHA are also anti-inflammatory and *pro-resolving* in low amounts. Mead acid doesn’t do this, nor many of the other functions that omega 3s play a large role in.

Omega 3, In *normal* amounts, are not immunosuppresive:

“In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries.”
Impact of fish oils on the outcomes of a mouse model of acute Pseudomonas aeruginosa pulmonary infection - PubMed

“Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S [Saturated high fat diet] after S. aureus-induced sepsis compared with that in mice treated with vehicle.”
Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis

“In addition, herring oil, DHA, and EPA at 20 μg/ml significantly decreased the hemolytic effect of S. aureus on human red blood cells, and when pre-treated to S. aureus, the bacterium was more easily killed by human whole blood. Transcriptional analysis showed that herring oil, DHA, and EPA repressed the expression of the α-hemolysin hla gene. Furthermore, in a Caenorhabditis elegansnematode model, all three prolonged nematode survival in the presence of S. aureus. ”
Herring Oil and Omega Fatty Acids Inhibit Staphylococcus aureus Biofilm Formation and Virulence

I could keep going, but you get the point.

I like that Ray Peat has challenged the status quo and has had some great ideas (restricting omega 6 PUFA is fantastic, as an example). But he isn’t right about everything, and has clearly developed heavy biases.

 

[Tarmander]

I disagree. It is well kown that what plays out in-vitro doesn‘t necessarily occur in vivo, and much less, in humans. Many of the in-vitro studies used very large doses as well.

We cannot say that becuase something has a negative effect at very high (essentially non-physiological doses: How could you get 30-60 g of fish oil a day naturally?), that it is “bad” and should be avoided.

1-3g of fish oil a day has repeatedly shown beneficial effects in the highest quality of evidence: Human RCTs.

More food for thought: Mead acid has 3 double bonds, same as the omega 3 fatty acid ALA. Thus, it is JUST as susceptible to oxidation as ALA. Yet, administering ALA has shown neuroprotective effects again and again. This is likely partly becuase ALA (and the other omega 3s) can get non-enzymatically oxidized to *anti-inflammatory* oxylipins, which appears to benefits the body in low amounts.

The prostaglandins produced from EPA / DHA are also anti-inflammatory and *pro-resolving* in low amounts. Mead acid doesn’t do this, nor many of the other functions that omega 3s play a large role in.

Omega 3, In *normal* amounts, are not immunosuppresive:

“In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries.”
Impact of fish oils on the outcomes of a mouse model of acute Pseudomonas aeruginosa pulmonary infection - PubMed

“Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S [Saturated high fat diet] after S. aureus-induced sepsis compared with that in mice treated with vehicle.”
Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis

“In addition, herring oil, DHA, and EPA at 20 μg/ml significantly decreased the hemolytic effect of S. aureus on human red blood cells, and when pre-treated to S. aureus, the bacterium was more easily killed by human whole blood. Transcriptional analysis showed that herring oil, DHA, and EPA repressed the expression of the α-hemolysin hla gene. Furthermore, in a Caenorhabditis elegansnematode model, all three prolonged nematode survival in the presence of S. aureus. ”
Herring Oil and Omega Fatty Acids Inhibit Staphylococcus aureus Biofilm Formation and Virulence

I could keep going, but you get the point.

I like that Ray Peat has challenged the status quo and has had some great ideas (restricting omega 6 PUFA is fantastic, as an example). But he isn’t right about everything, and has clearly developed heavy biases.

I mean I am with you. I hope fish oils are good for us and Ray's petridish studies are not really translatable. I can't really explain it better than Peat either, but I think, and many others think, his case is well laid out. The immune suppression from fish oils at dosages in the reasonable dosage range, plus the industry lobbying is concerning enough to warrant conservativism from supplementation. Would you at least say that the industry message that fish oils are great for everyone, so supplement up, is incorrect?

 

[Lollipop2]

Kammas said: ↑
in the recent one radio network interview posted today, Ray talks about seb derm and its relation to excess vitamin A from too much supplementation. The question is at around 1 hour and 7 minutes.

Has he talked about this before?! Or has he been reading my posts? LOL I suffered with seb derm for 15 years and then discovered on my own that low vA is basically the cure for it. I've never seen anyone else talk about vA and seb derm before.

A prime example of how smart - able to think not just parrot another’s thoughts, nuanced, and well researched Ray Peat is.

 

[postman]

I disagree. It is well kown that what plays out in-vitro doesn‘t necessarily occur in vivo, and much less, in humans. Many of the in-vitro studies used very large doses as well.

We cannot say that becuase something has a negative effect at very high (essentially non-physiological doses: How could you get 30-60 g of fish oil a day naturally?), that it is “bad” and should be avoided.

1-3g of fish oil a day has repeatedly shown beneficial effects in the highest quality of evidence: Human RCTs.

More food for thought: Mead acid has 3 double bonds, same as the omega 3 fatty acid ALA. Thus, it is JUST as susceptible to oxidation as ALA. Yet, administering ALA has shown neuroprotective effects again and again. This is likely partly becuase ALA (and the other omega 3s) can get non-enzymatically oxidized to *anti-inflammatory* oxylipins, which appears to benefits the body in low amounts.

The prostaglandins produced from EPA / DHA are also anti-inflammatory and *pro-resolving* in low amounts. Mead acid doesn’t do this, nor many of the other functions that omega 3s play a large role in.

Omega 3, In *normal* amounts, are not immunosuppresive:

“In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries.”
Impact of fish oils on the outcomes of a mouse model of acute Pseudomonas aeruginosa pulmonary infection - PubMed

“Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S [Saturated high fat diet] after S. aureus-induced sepsis compared with that in mice treated with vehicle.”
Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis

“In addition, herring oil, DHA, and EPA at 20 μg/ml significantly decreased the hemolytic effect of S. aureus on human red blood cells, and when pre-treated to S. aureus, the bacterium was more easily killed by human whole blood. Transcriptional analysis showed that herring oil, DHA, and EPA repressed the expression of the α-hemolysin hla gene. Furthermore, in a Caenorhabditis elegansnematode model, all three prolonged nematode survival in the presence of S. aureus. ”
Herring Oil and Omega Fatty Acids Inhibit Staphylococcus aureus Biofilm Formation and Virulence

I could keep going, but you get the point.

I like that Ray Peat has challenged the status quo and has had some great ideas (restricting omega 6 PUFA is fantastic, as an example). But he isn’t right about everything, and has clearly developed heavy biases.

Those studies are rather meaningless without a control group (EFAD group).

 

[gaze]

I’ve gone through his references on his website with fish oil. The vast majority were rats using diets of 10-20% of calories as fish oil (the human equivalant of 30-60 GRAMS of fish oil a day). One of the studies injected fish oil in large amounts directly into the brain...

This is not the same as getting 1-3 grams of fish oil a day from either fresh fish or a respectable brand of fish oil (in the early 200’s most of the fish oils in the market were already rancid by the time you bought them, and thus didn’t get good results.)

but 2 eggs and oysters give enough omega 3s if you need it, why would you ever take fish oil. They smell horrible.

 

[mrchibbs]

but 2 eggs and oysters give enough omega 3s if you need it, why would you ever take fish oil. They smell horrible.

Moreover, shellfish contains these fatty acids, along with tons of vitamins and minerals.

I can remember a decade ago I was popping these fish oil capsules like it was candy, on a daily basis, I cannot believe what sort of harm I may have done to myself. Surely enough, my health collapsed in my early 20s, after maybe 3-4 years of intense fish oil consumption. (10 capsules a day, on average)

It wasn't the only factor, but it certainly did not help.

 

[zarrin77]

Those studies are rather meaningless without a control group (EFAD group).

Those comparitive studies unfortunately do not exist. However, we do have evidence that EFAD impairs the immune system:

”These biochemical signs of omega 6 fatty acid deficiency were associated with impaired neutrophil function in vitro. Both migration responses and superoxide generation stimulated by N-formyl-methionyl-leucyl-phenylalanine were significantly decreased by 12 days of lipid-free TPN, as was the capacity of activated cells to synthesize leukotriene B4. In contrast, functional responses of fatty acid-deficient neutrophils to leukotriene B4 and phorbol myristate acetate, which have little or no effect on arachidonate release or metabolism, were not significantly altered. These findings indicate that endogenous supplies of arachidonic acid and other essential omega 6 fatty acids influence the functional responsiveness of neutrophils. These studies also indicate that altered neutrophil function is a feature of essential fatty acid deficiency and that it may contribute to the increased risk of infection and decreased inflammatory responses observed in this condition.”
Essential fatty acid deficiency and neutrophil function: studies of lipid-free total parenteral nutrition in monkeys - PubMed

“Essential fatty acid (EFA) deficiency is a predisposing factor for pulmonary infection with Staphylococcus aureus and Pseudomonas aeruginosa, the two major pathogenic microorganisms in cystic fibrosis (CF).”
Essential fatty acid deficiency and predisposition to lung disease in cystic fibrosis - PubMed

“Many abnormalities are described following essential fatty acid deficiency, such as cessation of growth, dermatitis, loss of hair, increased susceptibility to bacterial infections, histological abnormalities and disturbances of biochemical and physiological processes. These disorders can be explained as the result of a disturbed membrane structure and function, due to an abnormal serum fatty acid composition.”
[Essential fatty acid deficiency in childhood] - PubMed


And then, on a somewhat related note, here is a good review on the multitude of effects that omega 3 have on the brain (Specifically wrt dopamine):
N-3 (OMEGA-3) FATTY ACIDS: EFFECTS ON BRAIN DOPAMINE SYSTEMS AND POTENTIAL ROLE IN THE ETIOLOGY AND TREATMENT OF NEUROPSYCHIATRIC DISORDERS


Again, I’m not saying to chug down fish oil. But purposefully trying to target EFAD is not a strategy for health and logevity.

 

[tim333]

but 2 eggs and oysters give enough omega 3s if you need it, why would you ever take fish oil. They smell horrible.

CLO is a cocktail of vA toxicity, rancid PUFA and oxysterols. I would imagine fish oil has plenty of rancidity also?

It's quite a broken approach fortifying food or supplementing with nutrients. Iodine can be added to salt and children can receive fish oil and "oh we better take some selenium". "Just eat some eggs and fish!"

 

[Potato]

CLO is a cocktail of vA toxicity, rancid PUFA and oxysterols. I would imagine fish oil has plenty of rancidity also?

It's quite a broken approach fortifying food or supplementing with nutrients. Iodine can be added to salt and children can receive fish oil and "oh we better take some selenium". "Just eat some eggs and fish!"

What about those kids who have seafood and egg allergy?

 

[mrchibbs]

What about those kids who have seafood and egg allergy?

That used to be me. Max allergies to everything, cats, dogs, nuts, fish, eggs, shellfish, mold, dust, pollen etc.

They disappeared in my teens only to come back now in my late 20s after years of illness.

Still, I can eat loads of shellfish, seafood, eggs now. I get good quality stuff though.

 

[Potato]

Just got my vitamin A test results. My result is 1.7 micromol/L and the reference range is 0.7-4.2. So I don't think vitamin A toxicity is my problem.

 

[Jessie]

Interesting reading low A testimonies. Nevertheless I think it's important for people to keep in mind vitamin A is a essential nutrient. And there's several mechanisms as to why people experience toxicity from it. For one, it must be balanced with vitamin D (vitamin D deficiency is exceedingly common). Secondly, the vitamin A molecule is unsaturated, much like PUFA. Therefore you also need vitamin E to prevent it's oxidation. Lastly, Ray has mentioned that people with low metabolisms have a lower threshold of vitamin A tolerance. So anyone with low metabolic rates will be more sensitive to smaller amounts of it.

 

[LLight]

"Finished and 86 hour dry fast which I did with the intention of healing my overly dry skin from being on accutane for 6 months.

Its truly amazing how effective this practice is, I have terribly dry skin on my arms and to a lesser extent my entire body from the medication and this single fast seems to have cleared it up a good 40%, will be jumping into another fast in two or so days to help clear the rest up.

3 1/2 days of fasting dry has done more for my skin than 5 multi day water fasts have done in the last month."​

 

[mmb82]

I figured people on this thread would be interested in Dr. Smith's latest vitamin A related YouTube video. It is about 37 minutes long. I have not looked into any of the studies he presents, so if anyone takes the time to, I'd be interested in hearing their thoughts.

 

[Potato]

I figured people on this thread would be interested in Dr. Smith's latest vitamin A related YouTube video. It is about 37 minutes long. I have not looked into any of the studies he presents, so if anyone takes the time to, I'd be interested in hearing their thoughts.

I wonder why he doesn't allow any comments in his videos...

 

[md_a]

That's likely involved, but folate isn't a main suspect. People also improve after prolonged sun exposure and the body stores of folate must be considerably more affected than the degree of contamination. It can be a case of Raj's 'internal malnutrition', but killcium [and laxarium (Mg)] dysregulation is more probable. Poison/"vitamin" A is dependent on various factors, different conditions are going to benefit from its restriction for sparing what's low, it's difficult to narrow it to a single nutrient because diverse conditions are being lumped together.

One person is improving from removing an allergenic food that led to chronic overactivation of the immune system and was messing up its metabolism; another could be stressed, depleted in ascourgic acid, peeric (PL) or uric (EN) acid will increase (tanka, 2019), perhaps burden molybdenum in the process, leaving the person unable to synthesize poisonoic acid; someone can have impaired cleavage of macabrotenoids (nice, it works) and they will start taxing the recyclants.

- Free Radical Mediated Oxidative Degradation of Carotenes and Xanthophylls

It probably stems from inflammation of unresolving infections (and what made the person susceptible to them), that tend to be barred at surfaces interacting with the environment (skin, mouth, stomach, intestines, lungs), which are tissues under control of this toxin. If nourishment has to be prioritized, sacrificing part of the skin integrity to maintain that of the gut or lungs is justifiable due to housing germs while having to be permeable (obstruction isn't a good alternative).

The liver not keeping up with the insults from the intestine and the metabolism suffering in consequence isn't rare either. Ramón mentioned somewhere one of his early experiences with antibiotics, that it provided marked relief and he noticed how much his metabolism had been suppressed without him realizing.

Just a few problematic substances present in the diet are enough to yield you an extensive list of foods to avoid when you combine the major sources. Those are not toxin bags (like carrots), they're being craved and have potential inconvenients that can be mitigated.
- Oxalate Toxicity

Yes, thanks for the comment, I thought the possibility of folic acid being neglected in the diet inspired from Ray Peat, because the other elements could be obtained more easily, although there may be a lack of B1, B2, zinc, magnesium, Vit D in the diet of many. I started eating like this around 2009, and recently in the last months I developed a kind of psoriasis on my elbows and knees, my hair gray faster, gum problems, acne, and so I may have accumulated a large amount of vitamin A. Beef liver no longer attracts me as in the past, a sign that it could be something. So I looked at my diet and noticed that I have not been able to cover the daily dose of folic acid for a long time and from what I have studied recently I think it is a vital element. As changes in the last month I started to include foods with folic acid plus a supplement Jarrow Formulas- Methyl Folate, more sun exposure because it's summer, a better ratio of calcium phosphate to each meal, oil Magnesium, and psoriasis in the elbows and knees has disappeared, acne has largely disappeared as well, the rest remains to be seen.I do not consider vitamin A toxic, for this reason, I try to understand how to use it without having toxicity problems from not using it properly. I am also curious to understand the role of aldehyde toxicity.

We Need to Talk about Aldehydes



...

Aldehyde Sources, Metabolism, Molecular Toxicity Mechanisms, and Possible Effects on Human Health

Abstract

Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.

https://www.tandfonline.com/doi/abs...scroll=top&needAccess=true&journalCode=itxc20