Vitamin A And Joint Pains

[Dante]

It can also screw around with copper levels. I would check copper and ceruloplasmin levels.

Doesn't vitamin A bring up ceruloplasmin levels so more iron efflux from cells and copper influx inside cells. Isn't that good ?

 

[Ella]

Doesn't vitamin A bring up ceruloplasmin levels so more iron efflux from cells and copper influx inside cells. Isn't that good ?

Yes, it does but it is way more complicated and many factors to consider.
I was specifically referring to Vitamin A supplementation and not retinol that you get from eating liver. If retinol is coming from eating liver, it comes together with its own carrier protein, also liver provides pre-formed CP, copper and zinc all complete with their carrier proteins and yes also iron that needs proper management again by copper.

Now it is well known in the research literature that there is an intimate relationship between copper, zinc and Vitamin A. I think we should by now all know that vitamin A and zinc are synergistic molecules. However Vitamin A and copper have an inverse relationship. So when copper is high, vitamin A will be low and visa a versa. Vitamin A is antagonistic to copper. When we eat liver, these minerals and vitamins are provided in the ratio that nature intended. However, if we are supplementing Vitamin A and the same can be said for zinc or copper then we upset this delicate balance and we can expect consequences. The following papers may help to understand.

Although interactions between Zn and Cu and between Zn and vitamin A have been well described, less is known about interactions between Cu and vitamin A. Retinol and Cu are stored preferentially in liver and carried in blood plasma bound to retinol binding protein and ceruloplasmin respectively (Goodman, 1984 ; Cousins, 1985). Complex interactions between retinol and Cu have been reported in chronic Cu poisoning in sheep (Moore et al. 1972), but little is known about interactions between Cu and vitamin A under more usual circumstances.

Also Adrenal hormones are required to produce ceruloplasmin. Underactive, exhausted adrenal glands or sluggish liver activity cause a decrease in ceruloplasmin production. As a result, copper is not properly bound and is less available to the body. So when we are being chased by that tiger, the production of CP will be inhibited. The copper bound to CP is tightly bound but the fraction bound to albumin is only weakly bound, so it will fall off its taxi and become un-useable and cause havoc.

Pituitary–Adrenal Regulation of Ceruloplasmin

Pituitary–Adrenal Regulation of Ceruloplasmin

Many other molecules will deplete copper and not just Vitamin A.

Sulphur: Egg Yolks are high in sulphur. The yellow colour in yolks is due to their sulphur content. Sulphur binds to copper and greatly facilitates its excretion. The higher serum levels that you are experiencing may indicate greater mobilisation of copper. We know from the literature that urine levels are not alway representative of what is ingested and there is great variance among people. Wilson's Disease and Menke's and perhaps other conditions may confound results.

Taking the egg yolks out of the diet may provide a two-punch hit. Lowering Hmcy and preventing further loss of copper. Just saying - you need to investigate. Hmcy is a neurotoxin and it in itself can result in an inflammatory milieu.

isoprostanes deplete copper and this takes us back to pufas AGAIN!!

Although isoprostanes have a short half-life, some of them have potent biological activities, especially in the lungs and kidney, and they may even function in normal physiology. They are believed to be useful markers for oxidative stress, and importantly they can be assayed by non-invasive means. Related compounds are formed from eicosapentaenoic and docosahexaenoic acids in animals and from α-linolenic acid in plants. Isoprostanes were first produced in the test tube as long ago as 1967, but it was more than twenty years later before it was realized that they were also formed in appreciable amounts in vivo and had important biological properties.

Isoprostane-like compounds, i.e. F3, A3 and J3 isoprostanes, the last two with cyclopentenone rings, are formed from the oxidation of eicosapentaenoic acid (20:5(n-3)) in the heart muscle of mice in vivo. In addition, brain tissue contains relatively high proportions of docosahexaenoic acid (22:6(n-3)), and this gives rise to isoprostane-like compounds that have been characterized and termed neuroprostanes. There is a special interest in F4 neuroprostanes, which appear to be promising biomarkers for a variety of neurodegenerative disorders, including Alzheimer's disease, multiple sclerosis and Huntington’s disease. Indeed, related compounds can be formed from any lipid with a 1,4,7-octatriene unit, although the additional double bonds in eicosapentaenoic and docosahexaenoic acids mean that there is a much wider range of products, even if the general mechanisms are the same. However, isoprostanes derived from omega-3 fatty acids are not easy to quantify in urine

Synthesis of isoprostanes in animal tissues in vivo is brought about by a series of free radical-catalysed reactions, most of which do not involve enzymes, and any fatty acid with three or more double bonds can be a substrate

Isoprostanes are believed to be valuable indicators of oxidative stress in animal tissues, which has been defined as "a disturbance in the prooxidant–antioxidant balance in favour of the former", i.e. there is an excessive production of lipid peroxidation products, which may be involved in the development or exacerbation of cancer, and cardiovascular and neurological diseases, for example. They have been detected in all biological fluids and tissues analysed to date. In particular, there is growing acceptance that measurement of the relatively stable F2-isoprostanes and their metabolites in urine is a reliable non-invasive approach to the determination of the degree of oxidative stress in patients.

The following is their implications in diabetes 2 and CVD

https://academic.oup.com/cardiovasc...ative-stress-and-cardiovascular-complications

Copper deficiency also implicated in CVD and heart disease.

Cardiovascular disease from copper deficiency--a history. - PubMed - NCBI

High Vitamin A levels can result in bone pain. Bones also require copper for collagen formation.

Here a case history of a women with copper deficiency. Notice the ferritin was 354 ng/mL This should have been enough the alert that copper was not right.

A decrease in the copper-dependent enzymes (ceruloplasmin and cytochrome-c) that aid in iron metabolism and transportation has been proposed as a potential factor for anemia (6). Mitochondria from copper-deficient animals are deficient in cytochrome oxidase activity and fail to synthesize heme from ferric iron and protoporphyrin at the normal rate, leading to mitochondrial iron accumulation (7, 8). The mechanism underlying neutropenia in hypocupremia remains unknown.

So we started off with Vitamin A and end up with copper deficiency.

Here is a case of a zinc denture cream and copper deficiency. How many people are using zinc creams for diaper rash, sunscreens etc.?

Nature Clinical Practice Neurology | When metals compete: a case of copper-deficiency myeloneuropathy and anemia | Article

Remove the food or supplement and see if the symptom or biomarker improves.

When it comes to supplementation, please know what you are doing, if you are low in copper then don't supplement vitamin A or zinc and careful with sulphur. Your are asking for trouble. A good diet should give you plenty of everything.

Improve the adrenals, control stress, inflammation, toxic metals, pufas and ceruloplasmin will come up with time. Meanwhile, stick to eating liver and oysters.

 

[Mito]

Doesn't Vitamin A and Zinc play together? Couldn't high doses of Vitamin A screw around with the Zinc balance in the body?

The transport, metabolism, and activity of Vitamin A are all zinc dependent.

 

[REOSIRENS]

Vitamin A gives me as joint pain as well because it lowers cholesterol... I think its best taken in very low doses or with pregnenolone

 

[Dante]

Yes, it does but it is way more complicated and many factors to consider.
I was specifically referring to Vitamin A supplementation and not retinol that you get from eating liver. If retinol is coming from eating liver, it comes together with its own carrier protein, also liver provides pre-formed CP, copper and zinc all complete with their carrier proteins and yes also iron that needs proper management again by copper.

Now it is well known in the research literature that there is an intimate relationship between copper, zinc and Vitamin A. I think we should by now all know that vitamin A and zinc are synergistic molecules. However Vitamin A and copper have an inverse relationship. So when copper is high, vitamin A will be low and visa a versa. Vitamin A is antagonistic to copper. When we eat liver, these minerals and vitamins are provided in the ratio that nature intended. However, if we are supplementing Vitamin A and the same can be said for zinc or copper then we upset this delicate balance and we can expect consequences. The following papers may help to understand.

Although interactions between Zn and Cu and between Zn and vitamin A have been well described, less is known about interactions between Cu and vitamin A. Retinol and Cu are stored preferentially in liver and carried in blood plasma bound to retinol binding protein and ceruloplasmin respectively (Goodman, 1984 ; Cousins, 1985). Complex interactions between retinol and Cu have been reported in chronic Cu poisoning in sheep (Moore et al. 1972), but little is known about interactions between Cu and vitamin A under more usual circumstances.

Also Adrenal hormones are required to produce ceruloplasmin. Underactive, exhausted adrenal glands or sluggish liver activity cause a decrease in ceruloplasmin production. As a result, copper is not properly bound and is less available to the body. So when we are being chased by that tiger, the production of CP will be inhibited. The copper bound to CP is tightly bound but the fraction bound to albumin is only weakly bound, so it will fall off its taxi and become un-useable and cause havoc.

Pituitary–Adrenal Regulation of Ceruloplasmin

Pituitary–Adrenal Regulation of Ceruloplasmin

Many other molecules will deplete copper and not just Vitamin A.

Sulphur: Egg Yolks are high in sulphur. The yellow colour in yolks is due to their sulphur content. Sulphur binds to copper and greatly facilitates its excretion. The higher serum levels that you are experiencing may indicate greater mobilisation of copper. We know from the literature that urine levels are not alway representative of what is ingested and there is great variance among people. Wilson's Disease and Menke's and perhaps other conditions may confound results.

Taking the egg yolks out of the diet may provide a two-punch hit. Lowering Hmcy and preventing further loss of copper. Just saying - you need to investigate. Hmcy is a neurotoxin and it in itself can result in an inflammatory milieu.

isoprostanes deplete copper and this takes us back to pufas AGAIN!!

Although isoprostanes have a short half-life, some of them have potent biological activities, especially in the lungs and kidney, and they may even function in normal physiology. They are believed to be useful markers for oxidative stress, and importantly they can be assayed by non-invasive means. Related compounds are formed from eicosapentaenoic and docosahexaenoic acids in animals and from α-linolenic acid in plants. Isoprostanes were first produced in the test tube as long ago as 1967, but it was more than twenty years later before it was realized that they were also formed in appreciable amounts in vivo and had important biological properties.

Isoprostane-like compounds, i.e. F3, A3 and J3 isoprostanes, the last two with cyclopentenone rings, are formed from the oxidation of eicosapentaenoic acid (20:5(n-3)) in the heart muscle of mice in vivo. In addition, brain tissue contains relatively high proportions of docosahexaenoic acid (22:6(n-3)), and this gives rise to isoprostane-like compounds that have been characterized and termed neuroprostanes. There is a special interest in F4 neuroprostanes, which appear to be promising biomarkers for a variety of neurodegenerative disorders, including Alzheimer's disease, multiple sclerosis and Huntington’s disease. Indeed, related compounds can be formed from any lipid with a 1,4,7-octatriene unit, although the additional double bonds in eicosapentaenoic and docosahexaenoic acids mean that there is a much wider range of products, even if the general mechanisms are the same. However, isoprostanes derived from omega-3 fatty acids are not easy to quantify in urine

Synthesis of isoprostanes in animal tissues in vivo is brought about by a series of free radical-catalysed reactions, most of which do not involve enzymes, and any fatty acid with three or more double bonds can be a substrate

Isoprostanes are believed to be valuable indicators of oxidative stress in animal tissues, which has been defined as "a disturbance in the prooxidant–antioxidant balance in favour of the former", i.e. there is an excessive production of lipid peroxidation products, which may be involved in the development or exacerbation of cancer, and cardiovascular and neurological diseases, for example. They have been detected in all biological fluids and tissues analysed to date. In particular, there is growing acceptance that measurement of the relatively stable F2-isoprostanes and their metabolites in urine is a reliable non-invasive approach to the determination of the degree of oxidative stress in patients.

The following is their implications in diabetes 2 and CVD

https://academic.oup.com/cardiovasc...ative-stress-and-cardiovascular-complications

Copper deficiency also implicated in CVD and heart disease.

Cardiovascular disease from copper deficiency--a history. - PubMed - NCBI

High Vitamin A levels can result in bone pain. Bones also require copper for collagen formation.

Here a case history of a women with copper deficiency. Notice the ferritin was 354 ng/mL This should have been enough the alert that copper was not right.

A decrease in the copper-dependent enzymes (ceruloplasmin and cytochrome-c) that aid in iron metabolism and transportation has been proposed as a potential factor for anemia (6). Mitochondria from copper-deficient animals are deficient in cytochrome oxidase activity and fail to synthesize heme from ferric iron and protoporphyrin at the normal rate, leading to mitochondrial iron accumulation (7, 8). The mechanism underlying neutropenia in hypocupremia remains unknown.

So we started off with Vitamin A and end up with copper deficiency.

Here is a case of a zinc denture cream and copper deficiency. How many people are using zinc creams for diaper rash, sunscreens etc.?

Nature Clinical Practice Neurology | When metals compete: a case of copper-deficiency myeloneuropathy and anemia | Article

Remove the food or supplement and see if the symptom or biomarker improves.

When it comes to supplementation, please know what you are doing, if you are low in copper then don't supplement vitamin A or zinc and careful with sulphur. Your are asking for trouble. A good diet should give you plenty of everything.

Improve the adrenals, control stress, inflammation, toxic metals, pufas and ceruloplasmin will come up with time. Meanwhile, stick to eating liver and oysters.

Ok ,lol, too much complexity.
Edit: a doubt - can tanking estradiol levels down forcefully by supps/AIs hurt ceruloplasmin levels ?Ray often talks about copper deficiency being implicated in age related diseases, i think it's more to do with low ceruloplasmin(a functional copper deficiency) levels with aging.

 

[Ella]

Ok ,lol, too much complexity.
Edit: a doubt - can tanking estradiol levels down forcefully by supps/AIs hurt ceruloplasmin levels ?Ray often talks about copper deficiency being implicated in age related diseases, i think it's more to do with low ceruloplasmin(a functional copper deficiency) levels with aging.

As estradiol corresponds with copper levels and Vitamin A is anti-estrogenic, then yes. If Vitamin A is antagonist to copper, then we would expect lower synthesis of the carrier protein ceruloplasmin. Less copper = less taxis.

The following study looks at the influence of estradiol on ceruloplasmin levels in over-stressed rats. Rats were injected with estradiol after ovaries were removed and ceruloplasmin increased. I know this study is probably justification for HRT but as ceruloplasmin is also an acute phase protein, it might be indicating that being subjected to the stress of ovary removal was more stressful than swimming till exhaustion or swimming til exhaustion plus removal of ovaries plus injection of estradiol was extremely stressful and CP increased. Peat says estrogen is a non-specific stress response hormone and is triggered just like histamine when organism or cells sense stress. So the fact that estradiol increases CP and that these are both acute phase proteins may not translate to a favourable response. I could not access the full paper even though it free.

It is generally accepted that estradiol raises both copper and ceruloplasmin. However, I have seen high estradiol in a male from pesticide exposure with extremely low copper and ceruloplasmin levels. He was also on large dose of zinc that did not do him any favours. Ceruloplasmin slow to come up, if liver is toxic. His ferritin levels extremely high = fatty liver and poor synthesis of CP.

I ask this question before somewhere on the forum whether it was possible to target estrogen too aggressively. I think this is what happened to me from eating so many tropical fruits, OJ and sugar. I think I either caused and imbalance with copper or depletion resulting in too low estrogen. I found I had to increase liver intakes and I think if I eat the liver ever day, I do better. I'll do hair testing to see exactly what I have done along with RBC and hormones.

ndian J Med Sci. 2004 Apr;58(4):150-4.
Effect of estrogen on plasma ceruloplasmin level in rats exposed to acute stress.
Ganaraja B1, Pavithran P, Ghosh S.
Author information
Abstract
BACKGROUND:

Plasma ceruloplasmin, a copper containing protein, belongs to a class called acute phase proteins. Reduced level of ceruloplasmin was associated with Wilson's disease and Menke's kinky hair disease in man, primarily affecting copper metabolism. Stress was known to increase Ceruloplasmin. Several stress associated changes were commonly observed in women at menopause and also those who underwent overiectomy. Present experiment investigated the effect of estrogen on ceruloplasmin level in acute stress.

AIMS:
To assess the estradiol induced changes in plasma ceruloplasmin concentration on exposure of the rats to acute stress.

SETTINGS AND DESIGN:
Acute stress was induced by forcing the rats to swim till exhaustion. The rats were overiectomised bilaterally to remove the primary source of sex hormones. And hormone replacement was done later.

MATERIAL AND METHODS:
Wistar albino female rats were used. Acute stress was induced before overiectomy, following recovery from surgery, and again after Estradiol Valerate injection (for 10 days) in same group of rats. The plasma ceruloplasmin was estimated immediately after stress during each stage--that is preoperative control, stressed control, after overiectomy and then following treatment with Estradiol Valerate.

STATISTICAL ANALYSIS USED:
Paired sample T test was applied to analyze the findings.

RESULTS:
We found lowest ceruloplasmin level after stress in overiectomised animals, while on substitution of estradiol the trend appeared to be reversed.

CONCLUSION:
The result suggested a direct effect of estrogen on hepatic ceruloplasmin production/release and this could account for some of the beneficial effects of hormone replacement therapy.

 

[YourUniverse]

Bump.

Have been having ~3oz of liver as part of breakfast for a little over a week, before which my liver intake had been extremely sporadic, and without vitamin A supplementation.

I have developed a sort of weird knee pain. It doesn't hurt when bent or fully extended, only when pressure is placed from the medial plane.

Vitamin A has been shown to lower cortisol (And increase 5AR, and a few other seemingly nice things), could it be that I've had this knee pain/injury for some time, but that it was covered or suppressed by cortisol which is anti inflammatory? And now that the vitamin A is high, the cortisol has dropped, revealing the extent of the injury?

I think it was Ray that said age-related testosterone decreases have less to do with age per se, than having to do with the accumulation of injury and insult over time, and the necessary rises of cortisol to compensate. Something I'm pondering, could this be what's happening?

 

[ebs]

I eat a ton of sugar. If I eat sugar without niacinamide, it makes me anxious and irritable. Working on that and hoping to come down in dose.

For me it's the other way around... I need sugar with niacinamide for it to work properly (euforia, positive minded).

 

[japanesedude]

10000IU Vitamin A(orally) cracked my joints more than Androsterone and Vitamin K.

 

[LeeLemonoil]

Maybe joint and sceleton pain from Vitamin A is not (only) from Estrogen reduction:

Too much vitamin A may increase risk of bone fractures

Consuming too much vitamin A may decrease bone thickness, leading to weak and fracture prone bones, according to a study published in the Journal of Endocrinology. The study, undertaken in mice, found that sustained intake of vitamin A, at levels equivalent to 4.5-13 times the human recommended daily allowance (RDA), caused significant weakening of the bones, and suggests that people should be cautious of over-supplementing vitamin A in their diets.

 

[Hgreen56]

With high dose Vitamin A, 25,000 IU or more, I get joint pains. I always thought this was low estrogen before getting into the Peat world. Since I believe I have issues with vitamin A deficiency like keratinosis pilaris and acne, I would like to get more Vitamin A, but I'm not sure what causes these joint pains. Vitamin K2 doesn't seem to help, but I'm going to continue supplementing.

i see you still active here, how you doing? you solved the problem?

 

[GorillaHead]

I can tell u guys that i had the exact symptoms when i took too much zinc.

so perhaps it depletes copper somehow