Vitamin A And Osteomalacia

[Travis]

Just trying to get the word out that excessive Vitamin A is invariably associated with negative calcium balance and osteoporosis. Here are a few quotes from studies on this effect:
Excessive Dietary Intake of Vitamin A Is Associated with Reduced Bone Mineral Density and Increased Risk for Hip Fracture

Results: In multivariate analysis, retinol intake was negatively associated with bone mineral density. For every 1-mg increase in daily intake of retinol, risk for hip fracture increased by 68% (95% CI, 18% to 140%; P for trend, 0.006). For intake greater than 1.5 mg/d compared with intake less than 0.5 mg/d, bone mineral density was reduced by 10% at the femoral neck (P = 0.05), 14% at the lumbar spine (P = 0.001), and 6% for the total body (P = 0.009) and risk for hip fracture was doubled (odds ratio, 2.1 [CI, 1.1 to 4.0]).

Bone resorption activity of all-trans retinoic acid is independent of vitamin D in rats

The mechanism by which all-trans retinoic acid (ATRA) induces bone resorption is unknown. However, an interaction between vitamin A and vitamin D has been established....vitamin A has been shown to be a weak antagonist of the actions of vitamin D....Various bone parameters were measured after 3-8 wk. Regardless of the presence or absence of vitamin D(3), ATRA was able to cause bone resorption...Changes in dietary levels of Ca and P did not affect the ability of ATRA to cause bone resorption....Overall, the ability of ATRA to cause bone resorption is not dependent on vitamin D(3), dietary Ca or dietary P.

Vitamin A Intake and Hip Fractures Among Postmenopausal Women

Context Ingestion of toxic amounts of vitamin A affects bone remodeling and can have adverse skeletal effects in animals...A total of 72 337 postmenopausal women aged 34 to 77 years...After controlling for confounding factors, women in the highest quintile of total vitamin A intake (≥3000 µg/d of retinol equivalents [RE]) had a significantly elevated relative risk (RR) of hip fracture (RR, 1.48; 95% confidence interval [CI], 1.05-2.07; P for trend = .003) compared with women in the lowest quintile of intake (<1250 µg/d of RE). This increased risk was attributable primarily to retinol (RR, 1.89; 95% CI, 1.33-2.68; P for trend <.001 comparing ≥2000 µg/d vs <500 µg/d)...Beta carotene did not contribute significantly to fracture risk (RR, 1.22; 95% CI, 0.90-1.66; P for trend = .10 comparing ≥6300 µg/d vs <2550 µg/d). Women currently taking a specific vitamin A supplement had a nonsignificant 40% increased risk of hip fracture (RR, 1.40; 95% CI, 0.99-1.99) compared with those not taking that supplement, and, among women not taking supplemental vitamin A, retinol from food was significantly associated with fracture risk (RR, 1.69; 95% CI, 1.05-2.74; P for trend = .05 comparing ≥1000 µg/d vs <400 µg/d)

Retinol Intake and Bone Mineral Density in the Elderly: The Rancho Bernardo Study

Retinol is involved in bone remodeling, and excessive intake has been linked to bone demineralization...showed an inverse U-shaped association of retinol...supplement users had 0.02 g/cm2 (p = 0.02) lower BMD and 0.23% (p = 0.05) greater annual bone loss, and nonusers had 0.02 g/cm2 (p = 0.04) greater BMD and 0.22% (p = 0.19) greater bone retention...suggesting total intake is more important than source. In both sexes, increasing retinol became negatively associated with skeletal health at intakes not far beyond the recommended daily allowance (RDA)...

These are just truncated abstracts, but there was a really good study done at UW Madison that I will post below. The data is presented in table form, but I should be able to find time to graph some of it.

 

[Travis]

Here is the study: Vitamin A Antagonizes the Action of Vitamin D in Rats. They incinerated the bones of the mice and measured the mineral content after feeding increasing amounts of Vitamin A with or without Vitamin D. Here is the second set of data which illustrates how bone calcium increases with Vitamin D and decreases with Vitamin A:

This is only after 21 days, but you can see the trend. Bone density is clearly a function of Vitamins A and D.

 

[Travis]

The Linus Pauling Institute recommends:

...taking a multivitamin/mineral supplement that provides no more than 2,500 IU (750 μg) of preformed vitamin A...

, essentially setting the Food and Nutrition Board's RDA as the recommended upper limit. The FNB's tolerable upper intake level is officially set at 3,000 micrograms.

The foods with appreciable retinol contents seem to be fish, eggs, cheese, and liver. High intakes of these foods coupled with low Vitamin D intakes (extreme latitudes) may help to explain the osteoporosis prevalence among countries:

 

[paymanz]

I been worry about this too,however I recently seen this study showing vitamin A has no problem for bones if adeque vitamin D be available.
Vitamin A Intake, Serum Vitamin D and Bone Mineral Density: Analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008–2011)

But of curse I think the vitamin A dosage in that study is not that high..

 

[Travis]

Yes, the highest average intake group in the Korean survey study was only 1353 micrograms. The authors did not make clear what they mean by "Vitamin A". Did they assess beta carotene intake as well as retinol? And if they did, what conversion factors did they use? I wish they would have made this clear.

Most studies, especially the ones where people supplement, show a correlation. But most studies in which they actually measured Vitamin D as well, show that it does offer some protection.

Just as long as people don't go crazy with liver, supplements, and cheese they should be OK; most people here avoid eating fish anyway. Vitamin A is certainly the vitamin with the narrowest therapeutic range, and this should be made clear. Many studies show negative consequences at only 2-3x the RDI.

 

[paymanz]

I think ray reccomends high vitamin A only when you get high sun light exposure, as UV rays destroy it.

I haven't read that study entirely.

 

[Peater Piper]

I'm wondering what the ratio of D to A needs to be to obtain protection. Cod Liver Oil does not seem to have an adequate ratio imo, which seems to be about 1:10. It's also worth noting that in locations near the equator (and farther from the equator during summer months), assuming adequate cholesterol, a very large amount of D can be produced from some midday sun, and the intense UV rays can degrade Vitamin A at a high rate. In locations far from the equator, not only are people producing inadequate levels of Vitamin D, but covering a lot of the skin due to cooler weather probably prevents the degradation of the Vitamin A stores, which throws off their ratio even further.

 

[paymanz]

in regard of ratio ,Chris masterjohn has good information.haidut also has some post on that.

Also K and E having their roles in this interaction as well.chris has a good informative video on YouTube about this.

 

[Travis]

Yes, all of the fat-soluble vitamins seem to influence each other. The safest one seems to be Vitamin K. There is a Wikipedia page on Hypervitaminosis A, Hypervitaminosis D, and Hypervitaminosis E.

Apparently, there is no such thing as Hypervitaminosis K.

Dairy has a very high Vitamin A/Vitamin D ratio.

 

[aarfai]

in regard of ratio ,Chris masterjohn has good information.haidut also has some post on that.

Also K and E having their roles in this interaction as well.chris has a good informative video on YouTube about this.

Hey Payam would you be willing to post these preferred ratios?

 

[paymanz]

Hey Payam would you be willing to post these preferred ratios?

I should look at those info again honestly,but if I remember right it is 1:3 d:a but check it you're of,check haiduts post.
I personally don't go more than 5k vitamin A a day usually.and same for vitamin d.my ratio more is 1:1,but idk that might not be optimal.

I think even red light or infrared light helps to utilize larger amounts of vitamin A.

 

[Travis]

For what it's worth, here are the Linus Pauling Institute recommendations and derived ratio in international units: 2,500 IU/2,000 IU = 5/4 [A/D]

 

[Giraffe]

Dairy has a very high Vitamin A/Vitamin D ratio.

Unless you eat quite a bit of fish, there is no way to get sufficient vitamin D from diet alone; unless the stuff is fortified (then it doesn't count as food source in my books). To look at vitamin A/vitamin D ratios in food does not make sense to me.

 

[Travis]

Well, if you get 100% RDA of Vitamin A from eggs, you also get 93% RDA of Vitamin D. Getting the full RDA of Vitamin A from cheese, leaves you with only 15% RDA Vitamin D.

If you believe that Vitamin D can ameliorate Vitamin A overload, then this may be something to consider.

There is no other natural food that I am aware of besides eggs, cheese, and liver that can give you too much Vitamin A. Getting an RDA of Vitamin A from eggs gives you a potentially protective dose of Vitamin D.

Subclinical hypervitaminosis A causes fragile bones in rats

However, in the 50 x C group, a characteristic thinning of the cortex (cortical area -6.5% [p < 0.001]) and reduction of the diameter of the long bones were evident (bone cross-sectional area -7.2% [p < 0.01] at the midshaft and -11.0% [p < 0.01] at the metaphysis), as measured by peripheral quantitative computed tomography. In agreement with these data and a decreased polar strength strain index (-14.0%, p < 0.01), the three-point bending breaking force of the femur was reduced by 10.3% (p < 0.01) in the 50 x C group.

Sure, the rats were fed megadoses for 12 weeks, but this goes with the trend. Vitamin A certainly has hormonal effects that seem to influence bone mineralization at high doses. Exactly what causes higher rates of osteoporosis in the Nordic countries is debatable, but it could certainly be high amounts of Vitamin A from dairy exacerbated by low Vitamin D.

 

[Giraffe]

Well, if you get 100% RDA of Vitamin A from eggs, you also get 93% RDA of Vitamin D. Getting the full RDA of Vitamin A from cheese, leaves you with only 15% RDA Vitamin D.

If you believe that Vitamin D can ameliorate Vitamin A overload, then this may be something to consider.

There is no other natural food that I am aware of besides eggs, cheese, and liver that can give you too much Vitamin A. Getting an RDA of Vitamin A from eggs gives you a potentially protective dose of Vitamin D.

So you would eat 10-20 eggs a day to get the RDA for vitamin D?

It would be better to get vitamin D from sunlight's action on the skin if you can, wouldn't it?

Office of Dietary Supplements - Vitamin D
Egg, whole, raw, fresh Nutrition Facts & Calories

Regarding getting too much vitamin A from food... The RDA in the US is 3,000 IU (= 900 RAE) for men. The tolerable upper intake level is 10,000 IU. IIRC Peat thinks you need anything from 5,000 IU upwards (depending on thyroid function and sun exposure). Assuming 1,000 IU retinol in non-fortified full-fat milk, you would need:

• 3 liters to meet RDA
• 10 liters to hit the tolerable upper intake level
• a minimum of 5 liters to meet Peat's recommendations

to get the vitamin A from milk.

Vitamins in milk
Vitamin A

I wouldn't overdo on liver or supplemental vitamin A. However people who don't eat liver and don't convert beta carotene well (for example hypothyroid folk) need to make sure they get enough preformed vitamin A.

 

[EIRE24]

So you would eat 10-20 eggs a day to get the RDA for vitamin D?

It would be better to get vitamin D from sunlight's action on the skin if you can, wouldn't it?

Office of Dietary Supplements - Vitamin D
Egg, whole, raw, fresh Nutrition Facts & Calories

Regarding getting too much vitamin A from food... The RDA in the US is 3,000 IU (= 900 RAE) for men. The tolerable upper intake level is 10,000 IU. IIRC Peat thinks you need anything from 5,000 IU upwards (depending on thyroid function and sun exposure). Assuming 1,000 IU retinol in non-fortified full-fat milk, you would need:

• 3 liters to meet RDA
• 10 liters to hit the tolerable upper intake level
• a minimum of 5 liters to meet Peat's recommendations

to get the vitamin A from milk.

Vitamins in milk
Vitamin A

I wouldn't overdo on liver or supplemental vitamin A. However people who don't eat liver and don't convert beta carotene well (for example hypothyroid folk) need to make sure they get enough preformed vitamin A.

What about the people taking very high doses for acne? You'd suggest against it?

 

[Giraffe]

What about the people taking very high doses for acne? You'd suggest against it?

Not sure. Peat thinks too much vitamin A is anti-thyroid, and I have seen studies that confirm this. One explanation Peat gave is that thyroid hormone and vitamin A are carried on the same protein in the blood. I would look out for orange calluses on the palms of the hand and feet. With too little vitamin A you don't produce enough steroid hormones. I guess it's a matter of try and error to find out how much is optimal for you. If I planned to ingest high doses of vitamin A for longer than a few weeks I would definitely look into vitamin D as well. Peat said that vitamin E protects vitamin A, so I would make sure I have enough of this one.

I think there are a few threads about the relation between the fat-soluble vitamins, and Haidut based the mix in his product Estroban on studies.

 

[Travis]

Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Preformed Vitamin A (retinol and retinyl esters) bythe European Scientific Committee on Food

Moreover, RARs and RXRs show specific spatio-temporal patterns of expression in all developing systems during embryonic development, which suggests that retinoic acid signalling is involved in most, if not all, morphogenetic and patterning processes (Morriss-Kay and Sokolova, 1996).

Retinoic Acid is a powerful growth regulator.

The development of 6 reversible bulging fontanelle (BF) has been reported in a number of these studies...BF may represent the infant form of the headaches that are frequently reported during hypervitaminosis A in adults, and which may possibly arise from increased intracranial pressure (although it is actually not measured). In older children or in adults, the increased volume of the cerebro-spinal fluid can be linked to an increased intra-cranial pressure (Babikian et al., 1994).

It almost seems that intracranial pressure, dependent on Vitamin A, could be the factor that regulates skull expansion and growth during infancy.

In the most comprehensive available set of data, 41 patients were diagnosed with a vitamin A-induced hepatic pathology, at various levels of severity; nine (22%) died in less than 2 years following diagnosis and progression of the disease was demonstrated in 3 others...Mechanisms of hepatic effects are linked to overload of the storage capacity of the liver for vitamin A...producing collagen type III, and promoting fibrosis and potential cirrhosis.

It would almost seem that the liver absorbs Vitamin A too keep the blood levels at a certain level [see retinol binding protein]. Once the liver becomes saturated, the plasma levels increase and fibrosis can ensue. Alcohol potentiates hepatic Vitamin A injury.

Several isolated cases of skeletal problems in children with severe hypervitaminosis A have been reported (reviewed in Biesalski, 1989). Bone symptoms involve a decrease in density, osteoporotic changes and cortical thickening of the long tubular bones, leading to retarded growth.

And of course the nutritional committee discusses it's effect on bone.

A molecular interaction of vitamin A and vitamin D could also be responsible for the antagonism of vitamin A towards the action of vitamin D reported in rats (Rohde et al., 1999). A recent trial on 9 human healthy volunteers receiving either 15 mg of retinyl palmitate (8250 ug RE), or 2 µg of 1,25(OH)2D3 vitamin D, or a mixture of both, indicated that retinyl palmitate antagonizes the rapid calcium 9 response to physiological levels of vitamin D (Johansson and Melhus, 2001). These data suggest that excessive vitamin A may increase bone resorption and decrease bone formation (Binkley and Krueger, 2000).

Antagonizes Vitamin D..

The teratogenic effects of retinoic acids, the active oxidized metabolites of vitamin A, have been known for a long time and documented both in animals and in humans. Children exposed in utero to isotretinoin (13CRA) exhibit a pattern of congenital malformations, known as “the retinoic acid syndrome”, which includes defects of the craniofacies (small or absent external ears and auditory canals, cleft palate, micrognathia, low set ears), of the central nervous system (micro- or anopthalmia, cerebellar or cortical defects, microcephaly), of the thymus and of the cardiovascular system (transposition of the heart vessels, aortic arch hypoplasia, ventricular septal defects) (Lammer et al., 1985; Chan et al., 1996; Sinning, 1998). The risk of these defects was 25 times higher in the exposed children,..Although the data represent a series of anecdotal cases, they confirm the link between excessive vitamin A intake and teratogenesis, which has been clearly documented in various animal species, including mice, rabbits, rats (Piersma et al., 1996) and non human primates.

The table on page 10 implies that the first month of gestation represents the most critical period.
Starting on page 12, they summarize in an apparent attempt at setting a maximum tolerable intake:

The duration of high intake averaged 7.17 ± 1.21 years (range 0.2-15 years). Interestingly, these authors reported that the most severely affected subjects, i.e. those with cirrhosis (n=13), had consumed significantly more vitamin A, both daily and in total, than the patients without cirrhosis. The lowest continuous daily consumption in patients with cirrhosis was 7500 ug RE/day taken over 6 years. A similar case (7500 mg RE/day for 6 years) has been reported more recently (Kowalski et al., 1994), in which progressive liver failure led to death of the patient. Cases of hepatotoxicity have not been reported below 7500 ug RE/day, and it can be hypothesized that this value might be the upper threshold of the storage capabilities of the liver.

The risk for hip fracture in Swedish women (Melhus et al., 1998) is doubled for retinol intake greater than 1500 g RE/day as compared to intakes less than 480 ug RE/day.

The authors found that the women taking daily more than 4500 mg RE of total vitamin A (from food and supplement) had a 3.5 times higher risk of giving birth to a child with cranial-neural-crest defects, than mothers ingesting less than 1500 ug RE/day. When the analysis was restricted to the supplemental intake of vitamin A only, the relative risk for mothers ingesting more than 3000 ug RE/day was 4.8 higher than those ingesting 1500 mg RE/day...The quantitative conclusion from the Rothman’s study was that 3000 ug RE/day of supplemental vitamin A can be considered as a threshold for teratogenicity

They ended up setting the maximum tolerable intake at 3000 ug/day. This is slightly higher than 3x the RDA, but twice the amount that has led to bone thinning in elderly and perhaps Vitamin D deficient Swedes and Norwegians.

 

[Travis]

But this map on Vitamin A intake looks identical to a map of osteoporosis prevalence:
Vitamin A deficiency - Wikipedia, the free encyclopedia

 

[schultz]

Chris Masterjohn talks about this subject quite a bit. He warns against excessive vitamin D supplementation. A lot of people supplement vitamin D now but get pathetically low amounts of pre-formed vitamin A. I'm not sure an ideal ratio has been figured out yet, but I would definitely keep my vitamin A at least as high as my vitamin D. So if you supplement 5,000 IU of vitamin D per day you likely should be getting at least 5,000 IU of vitamin A as well. Personally though, I aim more for 3 to 1 ratio, though I'm not anal about it or anything. I would love to see good research on this though.

Vitamin A On Trial: Does Vitamin A Cause Osteoporosis? - Weston A Price

Update on Vitamins A and D - Weston A Price