Quote from Navid on April 22, 2024, 3:00 pm

Quote from tim on April 22, 2024, 2:33 am

Vitamin A and Pregnancy: A Narrative Review

In a study with animals, severe VAD during pregnancy was associated with fetal renal agenesis [89], whereas mild VAD led to a decrease in kidney weight and the number of nephrons in the newborn [106]. Based on these findings, a study was conducted in 16 mothers with VAD and 64 mothers with vitamin A sufficiency. Newborn babies of the mothers with VAD had significantly lower mean retinol levels and the dimensions of both kidneys were smaller than those of the newborns of mothers with vitamin A sufficiency [63]. A recent systematic review found an association between vitamin A deficiency in pregnancy and a negative effect on kidney function and kidney structure in the child [107].

Even mild VAD may affect the kidney size of offspring.

@tim-2

From the study linked above, it states

Studies in humans suggest that low or excessive levels of vitamin A in the diet during pregnancy can result in adverse effects on the fetus [9]. Thus, a recent study evaluated 1180 pregnant women in the first trimester and observed that 48 newborns presented congenital malformations. The serum concentrations of selenium, zinc, magnesium, and vitamins A, E, B12, and folic acid were assessed, and were significantly lower in mothers of newborns with congenital malformations than in the mothers of newborns without malformations, thus highlighting a possible association between congenital malformations and VAD

When these studies are analyzing serum concentrations of vitamin A, are they controlling for the levels of other nutrients? Otherwise, isn't it possible that VAD is simply a correlate of other deficiencies, and that those other deficiencies are the true causes of congenital malformations?

Quote from tim on April 22, 2024, 9:08 pm

@navid

Reduced teragenicity of VAD by giving vitamin A has been demonstrated.

Teragenicity has been replicated in animals devoid of retinoic acid receptor function.

Quote from tim on April 22, 2024, 10:25 pm

@joe-2

Yep but it doesn't matter what my opinion is. What matters is that there is strong evidence for it being essential and I haven't seen anything that refutes the body of evidence.

Questioning scientific evidence and theories is healthy but for one to form a bias that vitamin A is non essential is not reasonable. It's not dissimilar to forming a bias that the earth is flat just because of an article written by a flat earther that one has read.

Because there is no way to test serum for liver retinyl levels I do see vitamin A depletion along with regular testing of serum retinol becoming a widespread health practice in the future. Once serum retinol indicates liver stores are becoming depleted then one will be able to go back onto a regular diet. Most will probably choose to permanently avoid large amounts of dairy products and high carotenoid foods though.

The CARET study and similar studies have shown that not just high retinoid intakes but also high carotenoid intakes (to a lesser degree) are toxic. I think it's reasonable to permanently reduce butter, cream, cheese, carrots, pumpkin and sweet potato in the diet.

The idea that dietary vitamin A intakes are responsible for the rising rates of disease over the last few decades is incorrect for the simple reason that total mean vitamin A intakes have decreased. Liver and high fat dairy consumption has declined while beta carotene intakes have increased.

Vitamin A supplementation has increased but only a subset of the population supplements to a significant degree.

People following fad extreme diets are often poisoning themselves with retinyl and beta carotene but the rest of the population is consuming less vitamin A than a few decades ago.

It's true however that we are depleting less now though due to less smoke and sunlight exposure. So it is possible that vitamin A stores have increased since then on average due to that.

Liver retinyl stores were high early last century though due to widespread cod liver oil use and that wasn't associated with a rise in autoimmunity and liver dysfunction comparable to the rise over the last few decades as far as I know.

 

Quote from David on April 22, 2024, 10:54 pm

Quote from jjk_learning on April 22, 2024, 7:14 am

Quote from David on April 22, 2024, 1:13 am

@joe-2

First I thought, as a serious question about any early pig studies:
Who cares about pigs?
-Who takes really good care of any pig?

Even most Germanic languages have mostly negative proverbs and idioms about pigs like:
•As sick as a pig.
•Choosy pigs never get fat. [a proverb not taken from the link below]
•It ain't fitting to roll with a pig.
https://owlcation.com/humanities/pig-idioms

Then in the 1935 Hale study, which you attached in your post, they had only a subjective measurement of what vitamin A deficiency was:

"Symptoms of vitamin-A deficiency in the gilts at the time of breeding were evidenced by their wobbly gait, weaving, and crossing of the hind legs at the walk, drooping of the ears, and loss of weight. After the gilts were bred, they remained on the vitamin-A-free ration for the first 30 days of the gestation period, the time during which it is known that the eye develops in the pig embryo. After the first 30 days of the gestation period had passed, the gilts were given an abundance of vitamin A in the form of cod-liver oil, so as to furnish them every opportunity to complete a full gestation period."

"DR. FREDERICK H. VERHOEFF : I should like to ask if it ever failed when you tried to do that [induce vitamin A deficiency birth defects]?
MR. HALE : Yes, it has, but it is hard to tell when these animals are depleted to the state where vitamin A is practically depleted out of the body. You have to observe that yourself and be enough of an animal husbandman to know the symptoms exhibited by those pigs with vitamin-A deficiency. I doubt if anyone who is not familiar with pigs showing vitamin-A deficiency could ever succeed, except through trial and error for a good many periods.
   We succeeded the very first effort we made, after we selected young gilts the same age and weight of the first gilt. When we failed, it was with mature animals. We thought the one-hundred-and-sixty-day period on which we kept the first gilt was of some significance, but found it is not of any significance. The important feature is to deplete the animal to a very low state in vitamin A. We kept mature animals on a deficient ration for one hundred and sixty days and failed, but never have failed when we withheld breeding until the animals showed depletion, by these vitamin-A symptoms, to a very low state."

Why would any real scientist blindly assume that the cause of vitamin A deficiency is the only cause of these seemingly neurolical birth defects?

From looking at a more modern case study from 2018 they mention that there could several other reasons for microphthalmia and I don't think any of these older studies have excluded the possibility of any other possibilities than vitamin A deficiency.
-On top of theat who measures retinoic acid in any of these studies or wonder where the retinol that is usually very high in the liver have gone?

This more recent case study from 2018 is called:
"Congenital Microphthalmic Syndrome in a Swine"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033249/

"A long-established cause of microphthalmia in swine is hypovitaminosis A [4–6]. Other known or suspected causes include gestational-acquired infections, drugs, and environmental pollutant toxicities [7, 8]. More recently, various genetic aberrations ranging from chromosomal duplications to mutations in a single gene SOX2 [8] were identified to be implicated in microphthalmia development in humans and other animal species.

Teschen/Talfan disease is caused by the ubiquitous Teschovirus A (previously classified as Serogroup 1 porcine enterovirus), a nonenveloped ssRNA(+) virus in the order Picornavirales, family Picornaviridae. There are 13 serotypes (PTV-1 to -13) [9] of different pathogenicity, but all of them exhibit gastrointestinal and neurotropism. Both domestic pigs and wild boars are the only known hosts [10].

"Apart from hypovitaminosis A, several other causes of microphthalmia were reported, including suspected drug toxicities and high levels of selenium in diet [7]. Hereditary microphthalmos has been reported in Yorkshire pigs [1], White Shorthorn cattle, Jersey calves, and Hereford cattle (as a part of encephalopathy-microphthalmos syndrome). The pattern of heritability seems to be autosomal recessive trait in all cases listed above [7]."

Thank you for this analysis, David.

I'm going to try to restate what you're saying to see if I'm comprehending it the way you are laying it out.

1. Pigs and humans are very different, so the relevance is questionable.
2. The "Vitamin A deficiency" was purely subjective, not any kind of outright measurement of Vitamin A levels. Therefore the "deficiency" could have been any number of nutritional issues. And on top of that... since the "deficiency" was marked as a deficiency only once the pigs started having myriad health issues, it makes sense that the pigs born to sick mothers would have defects. Circular reasoning: "Despite depleting them of Vitamin A for 160 days, they aren't deficient because we don't see them sick yet. Once they're sick and feeble, then we will know they are Vitamin A deficient and breed them."
3. There are no measurements to show serum retinol levels or anything similar.
4. 80 years later, there are other known causes of the same defects showing up in pigs and these were not known to be investigated or controlled for at the time of the original studies.

Does that do a decent job at capturing what you are laying out?

@joe-2
I think you made quite a good summary of what I tried to convey but I have some additional thought on your four points:

1. Pig and humans are fairly similar, people have gotten pig heart valve transplants for over 30 years:
   "For over 30 years, pig valves have been successfully planted in humans. Interestingly, a pig’s heart is similar in size, weight, and structure to a human’s heart."
   https://www.heart-valve-surgery.com/learning/pig-valve-replacement/
   My point was that if animals are mistreated they get sicker and then even the controls are more sick lowering the baseline of health in the animals. How many really cares about pigs, or production units as some farmers call them, and takes good care of them? This is not isolated to just pigs but my point is that we even use pigs in many proverbs and idioms as something purely negative. Don't be a pig for example.
2. In this particular study intentionally making pigs sick before breeding and then wonder why there are birth defects is just dumb. There have been positive effects of high vitamin A supplementation in humans as well but I think it is usually in malnurished African children, who probably carry on top of malnutrition some sort of disease. There have been thoughts mentioned here about vitamin A working against some pathogens through some toxicity. I would guess that in many warm and humid countries with minimal refrigeration they use chili and other strong spices in order to delay spoilage of their food.
3. Yes, Mr. Hale even said that their results was hard to replicate.
4. Yes, and these now other known causes could potentially worked in combination with this vitamin A "free" diet. As Grant Genereux showed the early studies never fed experiment animals a vitamin-A-free diet, and how could they with their primitive technics. Though I think it is unreasonable that the researchers didn't think toxicity when some animals quickly got seriously sick instead of deficiency which I believe in comparison is a slower and more gradual process.

There was also the lack of information on what they fed the pigs and they could very well have fed these pigs liver and other waste from other slaugthered pigs, because who cares about pigs? Remember mad cow disease that came from feeding dead cows to growing cows?

See the 1928 study mentioned in the 1935 Hale paper:
"Nerve Degeneration Resulting from Avitaminosis A"
https://doi.org/10.1093/jn/2.2.183 (available at sci-hub)

"In our studies (1928) of the importance of vitamin A for swine, six lots, including twenty-seven individuals, have been fed a ration which is deficient in vitamin A. This ration consisted of white corn, tankage [slaughter waste blood], and bone ash. Complications from rickets were avoided by allowing the pigs an outside yard where they received an abundance of direct sunshine. The pigs were placed on this vitamin A-deficient diet at weaning time and were continued on the diet until they died, or until they reached such an advanced stage of the disorder that they would have died in a few days, when they were killed for post-mortem examination."

For those more interesting in what tankage, meat scraps and meat meal are - there is this 1928 paper:
"What are Tankage, Meat Scraps and Meat Meal"
https://doi.org/10.3382/ps.0080011

"In 1900 a product for swine feeding was made from bones and meat trimmings which were immediately tanked, pressed and dried. Plumb and Van Norman6 in 1900 reported favorable results from feeding this tankage as a supplement to corn. As a result of continued favorable results today almost all of these residues are used for feeding purposes. Clemen1 states that at least 90 per cent of the high grade tankage and 75 per cent of the blood manufactured by national packers are now used in animal feeds."

Quote from Joe2 on July 28, 2025, 5:56 pm

 

"In 1900 a product for swine feeding was made from bones and meat trimmings which were immediately tanked, pressed and dried. Plumb and Van Norman6 in 1900 reported favorable results from feeding this tankage as a supplement to corn. As a result of continued favorable results today almost all of these residues are used for feeding purposes. Clemen1 states that at least 90 per cent of the high grade tankage and 75 per cent of the blood manufactured by national packers are now used in animal feeds."

Well played.  @david

Are you still on here?