Quote from Dr. Garrett Smith on March 3, 2019, 2:45 pm

If you aren't familiar with my body of work yet, I believe that chronic Vitamin A toxicity aka chronic hypervitaminosis A is a worldwide epidemic (and it isn't really a vitamin at all), and that Vitamin D *supplements* or large amounts of Vitamin D by mouth (think cod liver oil, which also contains Vitamin A) are toxic to all creatures big and small.  That intro will help what I'm about to explain make more sense.  For the rest of this article, I'll be referring to these two troublemakers as Poison/"Vitamin A" and Hormone D (I often refer to it as Hormone D because your body makes it and you shouldn't have to get it from your diet...like ALL your other hormones!).

We need bile to help us absorb fat-soluble compounds, this is true and accepted.  If our body encounters fat-soluble things that it WANTS, it would make sense that it would make MORE bile to opportunistically absorb as much as possible, right?  So why then does the body do the EXACT OPPOSITE?  This first paper is going to be the evidence that your body DOESN'T WANT EITHER OF THEM FROM THE DIET:

Regulation of Bile Acid Synthesis by Fat-soluble Vitamins A and D

Bile acids are required for proper absorption of dietary lipids, including fat-soluble vitamins. Here, we show that the dietary vitamins A and D inhibit bile acid synthesis by repressing hepatic expression of the rate-limiting enzyme CYP7A1. Receptors for vitamin A and D induced expression of Fgf15, an intestine-derived hormone that acts on liver to inhibit Cyp7a1. These effects were mediated through distinct cis-acting response elements in the promoter and intron of Fgf15. Interestingly, trans-activation of both response elements appears to be required to maintain basal Fgf15 expression levels in vivo. Furthermore, whereas induction of Fgf15 by vitamin D is mediated through its receptor, the induction of Fgf15 by vitamin A is mediated through the retinoid X receptor/farnesoid X receptor heterodimer and is independent of bile acids, suggesting that this heterodimer functions as a distinct dietary vitamin A sensor. Notably,vitamin A treatment reversed the effects of the bile acid sequestrant cholestyramine on Fgf15, Shp, and Cyp7a1 expression, suggesting a potential therapeutic benefit of vitamin A under conditions of bile acid malabsorption. These results reveal an unexpected link between the intake of fat-soluble vitamins A and D and bile acid metabolism, which may have evolved as a means for these dietary vitamins to regulate their own absorption.

The only way the above pattern makes sense is if the body believes that Poison/"Vitamin A" and Hormone D are TOXIC, and that the body has been built to reduce its ability to absorb them when they are eaten.  It is solely a protective mechanism, "to regulate their own absorption".  Note that this didn't start at toxic levels, it started IMMEDIATELY.

It is known that a specific enzyme (lipase, fat-related enzyme) in bile salts is key to Poison/"Vitamin A" uptake in the gut:

Retinyl ester hydrolases and their roles in vitamin A homeostasis

The bile-salt activated carboxyl ester lipase (CEL; EC 3.1.1.13) has long been known to exhibit broad substrate specificity (reviewed in [22]) and was considered as key enzyme in intestinal retinol uptake.

On to the next inquiry.  What if bile salts "potentiated" (increase the power, effect, or likelihood of something, especially a drug or physiological reaction) the toxicity of Poison/"Vitamin A"?

Potentiating effects of DPPD, bile salts and sulfasuxadine on hypervitaminosis A in the rat.

I can't find access to even an abstract for the above paper online, and I don't have time to go to the University of Arizona Health Sciences Library to find a hard copy.  I'm going to say that the title says enough for me!  Bile salts potentiate (increase) the negative effects of hypervitaminosis A in rats!  Bile salts make the entire situation worse, in effect.

Here's what we have so far:

• Consumption of Poison/"Vitamin A" (and Hormone D) from oral sources causes the body to REDUCE bile production/release.
• A key enzyme for absorbing Poison/"Vitamin A" from the gut is in bile salts.
• It has been shown that bile salts specifically increase the damaging effects from Poison/"Vitamin A" toxicity.

Now, does it make sense why the body slows down its bile production when Poison/"Vitamin A" is coming in?  This is showing a pattern of the body trying to PROTECT itself from a poison/toxin!

Note that Hormone D also inhibited the process as well, from the first paper above.  It also fits the pattern.  Maybe you had gallbladder issues show up sometime after you started high-dose Vitamin D supplements and/or cod liver oil?  There are NO coincidences.

Now, let's establish the pattern that excess Poison/"Vitamin A" and Vitamin D *supplements* cause liver and gallbladder disease in animals and humans.

It is likely that the mechanism of the damage that both Poison/"Vitamin A" and Hormone D supplements cause is through their physiological effect of causing hypercalcemia (excess calcium in the blood) when either or both of them is present in excess. Hypercalcemia has been linked to causing gallbladder stones (cholelithiasis).

What if during hypercalcemia, the body REDUCED its production of bile, possibly to reduce the absorption of Poison/"Vitamin A" and Hormone D from the diet?  That would also seem to make sense:

Bile secretion in acute and chronic hypercalcemia in the cat.

The reported coincidence of primary hyperparathyroidism and cholelithiasis led us to investigate the effects of acute and chronic hypercalcemia on bile secretion in cats. Acute hypercalcemia (6-7 mmol/liter) was induced by an intravenous calcium infusion. Chronic hypercalcemia (3-4 mmol/liter) was induced and maintained for 8-10 weeks by treatment with subcutaneous vitamin D3, oral dihydrotachysterol, and feeding a calcium-rich diet.

Chronically excessive calcium in the blood was maintained by Vitamin D3 and calcium supplements.  What have certain doctors been pushing on people for osteoporosis?  Make sure you keep this in mind when you see the "cod liver oil and milk" (contains Poison/"Vitamin A", Hormone D, and tons of calcium) combination cased study mentioned further below!

Bile secretion was then studied in acute experiments. We found that calcium concentrations in serum and hepatic bile were similar during all experimental normo- or hypercalcemic conditions (y = 1.12x - 0.85; r = 0.76). Biliary volume outputs were significantly decreased during both acute (P less than 0.002) and chronic (P less than 0.05) hypercalcemia compared with normocalcemic controls. Acute hypercalcemia also decreased total bile acid outputs (P less than 0.05), but had no effect on biliary bile acid concentrations. The inhibitory effect of acute hypercalcemia on biliary fluid and bile acid secretion was dose dependent and not antagonized by atropine. These findings suggest that calcium is secreted in hepatic bile at similar concentrations as present in the serum and that elevations of serum calcium concentration inhibit biliary volume and bile acid secretion in cats. Similar effects of hypercalcemia on bile composition in humans might promote calcium salt precipitation in bile.

And hypercalcemia is associated with more stones in both the urinary system and gallbladder:

Diseases associated with hypercalcemia

Conclusion: The results of the study show an increasing risk of urolithiasis [stones anywhere in the urinary tract, including kidneys and/or bladder], cholelithiasis [gall stones], gastritis and peptic ulcer in patients with hypercalcemia. The results may indicate an important role of hypercalcemia in the pathogenesis of these diseases.

Poison/"Vitamin A" was used to INDUCE gallstones in hamsters.  Boy, this seems pretty straightforward:

Pigment cholelithiasis induced by vitamin A and its prevention by butylated hydroxytoluene.

We previously reported on the induction by vitamin A of gallstones, rich in calcium and phosphate, in hamsters. On the other hand, it has been reported that the phenolic antioxidant butylated hydroxytoluene (BHT) potentiates the hepatotoxicity of vitamin A. In the present work we have tested the effect of BHT on the lithogenicity of vitamin A and on bile composition. The urinary excretion of calcium and phosphate was determined to assess a possible asymptomatic bone resorption due to vitamin A toxicity, and/or an effect of BHT on the homeostasis of calcium and phosphate. Three groups of 18 male hamsters were fed with the following diets for 70 days: Group 1, Purina Nutricubes (DB); Group 2, DB + 25,000 IU% retinol acetate (DL); Group 3, DL + 500 mg% BHT. Vitamin A (Group 2) induced gallstones in 78% of the animals, increased bile flow and biliary phosphate and calcium concentrations, and reduced those of bile salt, cholesterol and phospholipid. BHT (Group 3) reduced gallstone frequency to 5.5%, and decreased biliary phosphate, calcium and lipids toward more normal concentrations. Vitamin A alone or with BHT did not significantly affect food intake or urinary excretion of calcium and phosphate.

If you read the above and get the idea you're going to take a bunch of BHT to "fix your problem", know that I don't endorse that idea and I'm not going to be using it ever.

Look at what the research said Poison/"Vitamin A" did in dogs, note the liver and gallbladder:

The effect of hypervitaminosis A and other dietary factors on the young pig

Hypervitaminosis A in the dog, which is apparently more resistant to vitamin A toxicity than rats and mice, was exam­ined by Haddock et al. (1949). The results were similar to those previously described above with rats, but in addition it was found that serum cholesterol increased as did lipoid phosphorus in the blood. Some liver necrosis was found [dead/dying liver tissue] and vascular lesions in the media of arteries and veins [atherosclerosis aka cardiovascular disease], myocardium [heart disease], gallbladder [there it is!], and urinary bladder were observed. Wheeler (1945) reported that diets high in vitamin A or vitamin A precursors [carotenoids, also Poison/"Vitamin A"] caused diarrhea in dogs. [diarrhea commonly goes with gallbladder disease, as there is a breakdown in fat metabolism and bile production, which causes steatorrhea aka fatty stools, aka diarrhea with an oily film on the top of the toilet water]

On to how Poison/"Vitamin A" causes teratogenic malformations (birth defects) in "almost all organ systems" in animal studies including the liver and gallbladder:

Vitamin A and carotenoid toxicity

In animal experiments, hypervitaminosis A produced malformations in almost all organ systems. The type and incidence of malformation depends on the stage of gestation and dose and, to a lesser extent, on the species and strain. Reported structural defects in animals include defects of the brain, spinal cord, face, eye, all parts of the ear, teeth, salivary glands, aortic arch, heart, lungs, gastrointestinal tract, liver, gallbladder, urinary system, genitalia, pituitary, thyroid, thymus, skull, vertebrae, ribs, extremities, muscles, and situs inversus [43, 44, 67–69]

Let's go on to Vitamin D supplements causing gallstones.

The gentleman below killed himself with a Vitamin D supplement combined with some mineral salts (taking the wrong minerals or supplements in combination with Poison/"Vitamin A" and/or what we call Hormone D will only speed the diseases that are coming!):

METASTATIC CALCIFICATION ASSOCIATED WITH HYPERVITAMINOSIS D AND HALIPHAGIA

The observation of a recent case of metastatic calcification, in which the patient ingested vitamin D and several inorganic salts, furnishes provoking problems for solution.

REPORT OF CASE 

A cab driver, 44 years old, born in Scotland, was admitted to St. Luke's Hospital in Denver under the care of Dr. C. R. Cooper, who kindly gave permission for use of the clinical details. Since the patient was comatose, the history was obtained from his wife, who stated that for about 6 months before admission and for little understood reasons he had been taking daily doses of a vitamin D preparation as well as liberal amounts of a mildly laxative compound containing sodium sulfate, sodium bicarbonate, sodium phosphate, and sodium chloride. His wife warned him repeatedly that this was a hazardous procedure without the advice of a physician, but he persisted in his autotherapy.
[...]
The liver weighed 2,280 gm. The capsule was thin. The cut section was firm, tan, and focally marked by pale yellow areas, 6 to 12 mm. in diameter. The biliary ducts and blood vessels were well preserved. The gallbladder had a smooth serosa, a fairly thin wall, a dark green mucosa, and contained one large, oval stone measuring 4.5 by 3.5 by 2.5 cm., which was rough, tan and dark green, and six dark green, faceted calculi [stones] measuring 5 to 6 mm. in diameter. The bile was thick and dark green. The pancreas was normal in size, firm, tan, and coarsely lobulated.[...]The parenchymal cells of the liver showed the finely foamy appearance of abundant glycogen. A few groups of liver cells contained coarse cytoplasmic fat vacuoles. The blood vessels were well preserved and contained no calcium. The periportal areas and the biliary ducts were intact. The perimuscular coat of the gallbladder revealed increased fibrous connective tissue and infiltrations of lymphocytes.

In case you're having trouble with the idea that Vitamin D *supplements* have been causing problems ever since the days of cod liver oil becoming a snake oil health fad, I'd highly suggest you read this paper documenting some of the human damage it has caused, both in our current Vitamin D3 cholecalciferol fad, as well as previously during the Vitamin D2 ergocalciferol fad:

Hypercalcemia and metastatic calcification

Their cavalier approach was repeated with more disastrous results after 1924 when high doses of tasteless ergocalciferol (vitamin D₂) from irradiated ergosterol became available and were indiscriminately prescribed for rheumatoid arthritis, tuberculosis, Paget's disease and chilblains, in none of which it has been shown to produce benefit, and osteoporosis.

The effects of overdosage were described within four years of high dose ergocalciferol being released for sale; the condition was reviewed in a cluster of papers in the early 1950's [1–3]. Diagnosis was often delayed because the commonest symptoms were the non-specific ones of hypercalcemia — nausea, vomiting, weight loss, colic, constipation, thirst, polyuria, headache, weakness, apathy and depression roughly in that order [1]. Once suspected, the diagnosis was confirmed by the presence of hypercalcemia and renal impairment.

Consequently the half-life of hypercalcemia, which is about 3 weeks when modest therapeutic overdose occurs [5], may be more prolonged in severe vitamin D toxicity [6]. One lady who took the Viking mixture of cod liver oil and milk required treatment for hypercalcaemia for 21 months after withdrawal of vitamin D [5]and another elderly lady intoxicated with ergocalciferol had elevated blood vitamin D and 25(OH) vitamin D levels after 17 months [7].

Cod liver oil and milk causing toxicity, you say?  This woman's "food-based" approach required 21 MONTHS of treatment to get her blood calcium level back to normal, you say?  Do you know of any nutritional groups/cults out there pushing these two in combination?  I do!  I have to repair people from those so-called "traditional diet" disaster recommendations every day.  Remember, the quickest recipe for hypercalcemia is Poison/"Vitamin A" + Hormone D by mouth + large amounts of calcium...or if you want to simplify and do a "food-based" poisoning, just consume cod liver oil and milk!  Maybe even throw in some liver for good measure, you'll get there even quicker!

Put simply, Poison/"Vitamin A" and Hormone D cause your gallbladder to under-function (ruining your digestion) and eventually cause gallstones.  It's all right there.  Adding large amounts of calcium to the mix causes the disaster to happen even sooner.

 

 

 

Let's go on to Vitamin D supplements causing gallstones.

The gentleman below killed himself with a Vitamin D supplement combined with some mineral salts (taking the wrong minerals or supplements in combination with Poison/"Vitamin A" and/or what we call Hormone D will only speed the diseases that are coming!):

METASTATIC CALCIFICATION ASSOCIATED WITH HYPERVITAMINOSIS D AND HALIPHAGIA

The observation of a recent case of metastatic calcification, in which the patient ingested vitamin D and several inorganic salts, furnishes provoking problems for solution.

REPORT OF CASE 

A cab driver, 44 years old, born in Scotland, was admitted to St. Luke's Hospital in Denver under the care of Dr. C. R. Cooper, who kindly gave permission for use of the clinical details. Since the patient was comatose, the history was obtained from his wife, who stated that for about 6 months before admission and for little understood reasons he had been taking daily doses of a vitamin D preparation as well as liberal amounts of a mildly laxative compound containing sodium sulfate, sodium bicarbonate, sodium phosphate, and sodium chloride. His wife warned him repeatedly that this was a hazardous procedure without the advice of a physician, but he persisted in his autotherapy.
[...]
The liver weighed 2,280 gm. The capsule was thin. The cut section was firm, tan, and focally marked by pale yellow areas, 6 to 12 mm. in diameter. The biliary ducts and blood vessels were well preserved. The gallbladder had a smooth serosa, a fairly thin wall, a dark green mucosa, and contained one large, oval stone measuring 4.5 by 3.5 by 2.5 cm., which was rough, tan and dark green, and six dark green, faceted calculi [stones] measuring 5 to 6 mm. in diameter. The bile was thick and dark green. The pancreas was normal in size, firm, tan, and coarsely lobulated.[...]The parenchymal cells of the liver showed the finely foamy appearance of abundant glycogen. A few groups of liver cells contained coarse cytoplasmic fat vacuoles. The blood vessels were well preserved and contained no calcium. The periportal areas and the biliary ducts were intact. The perimuscular coat of the gallbladder revealed increased fibrous connective tissue and infiltrations of lymphocytes.

In case you're having trouble with the idea that Vitamin D *supplements* have been causing problems ever since the days of cod liver oil becoming a snake oil health fad, I'd highly suggest you read this paper documenting some of the human damage it has caused, both in our current Vitamin D3 cholecalciferol fad, as well as previously during the Vitamin D2 ergocalciferol fad:

Hypercalcemia and metastatic calcification

Their cavalier approach was repeated with more disastrous results after 1924 when high doses of tasteless ergocalciferol (vitamin D₂) from irradiated ergosterol became available and were indiscriminately prescribed for rheumatoid arthritis, tuberculosis, Paget's disease and chilblains, in none of which it has been shown to produce benefit, and osteoporosis.

The effects of overdosage were described within four years of high dose ergocalciferol being released for sale; the condition was reviewed in a cluster of papers in the early 1950's [1–3]. Diagnosis was often delayed because the commonest symptoms were the non-specific ones of hypercalcemia — nausea, vomiting, weight loss, colic, constipation, thirst, polyuria, headache, weakness, apathy and depression roughly in that order [1]. Once suspected, the diagnosis was confirmed by the presence of hypercalcemia and renal impairment.

Consequently the half-life of hypercalcemia, which is about 3 weeks when modest therapeutic overdose occurs [5], may be more prolonged in severe vitamin D toxicity [6]. One lady who took the Viking mixture of cod liver oil and milk required treatment for hypercalcaemia for 21 months after withdrawal of vitamin D [5]and another elderly lady intoxicated with ergocalciferol had elevated blood vitamin D and 25(OH) vitamin D levels after 17 months [7].

Cod liver oil and milk causing toxicity, you say?  This woman's "food-based" approach required 21 MONTHS of treatment to get her blood calcium level back to normal, you say?  Do you know of any nutritional groups/cults out there pushing these two in combination?  I do!  I have to repair people from those so-called "traditional diet" disaster recommendations every day.  Remember, the quickest recipe for hypercalcemia is Poison/"Vitamin A" + Hormone D by mouth + large amounts of calcium...or if you want to simplify and do a "food-based" poisoning, just consume cod liver oil and milk!  Maybe even throw in some liver for good measure, you'll get there even quicker!

Put simply, Poison/"Vitamin A" and Hormone D cause your gallbladder to under-function (ruining your digestion) and eventually cause gallstones.  It's all right there.  Adding large amounts of calcium to the mix causes the disaster to happen even sooner.