Osteocalcin - Possibly Very Androgenic

Hans

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Osteocalcin, acts as a hormone and is able to increase testosterone, increase insulin and its sensitivity, as well as decrease fat mass by increasing energy expenditure.

Osteocalcin, (a.k.a. bone gamma-carboxyglutamic acid-containing protein (BGLAP)), is a noncollagenous protein hormone found in bone and dentin. Osteocalcin is secreted mainly by osteoblasts and a few other tissues, such as adipose tissue, and it was mainly thought to only aids in bone-building,

When the osteoblast releases osteocalcin, it's either in it's carboxylated or undercarboxylated form. The carboxylated form is when vjtamin K "activates" it so that it can aid in bone mineralization in the bone matrix. The undercarboxylated osteocalcin are released into the blood stream. Undercarboxylated are the hormonally active form of osteocalcin.

High levels (too high) of undercarboxylated osteocalcin are associated with:

  • high levels of adiponectin (better insulin sensitivity)
  • more insulin secretion (it stimulates the beta cells of the pancreas)
  • increased energy expenditure
  • lower fat mass
  • higher testosterone
  • impaired glucose metabolism (hyperinsulinemia and hypoglycemia) (1)
  • Soft tissue calcification (thats why you need vitamin K to carboxylate a fraction of osteocalcin to prevent negative effects)
Whereas too low levels of undercarboxylated osteocalcin is associated with:

  • hyperglycemia
  • hypoinsulinemia
  • insulin resistance
  • reduced energy expenditure
  • obesity
  • reduced testosterone levels
Both lower and higher total osteocalcin levels predicted increased all-cause mortality rates, with comparable associations for cardiovascular and noncardiovascular deaths. (2)



Testosterone
Undercarboxylated osteocalcin acts on the Leydig cells of the testis to stimulate testosterone biosynthesis via the bone-testis axis. The undercarboxylated osteocalcin binds to a G protein-coupled receptor (GPCR6A), which is expressed in the testis, and regulates StAR, Cyp11a, Cyp17 and 3β-HSD, cAMP and Cyp2r1 expression, through CREB as the transcriptional mediator which activates these enzymes. (3, 4, 5)

StAR are the rate limited enzyme that transports cholesterol from the outer mitochondria into the inner mitochondria of the Leydig cells to synthesize the precursor to all steroids, pregnenolone.

Cyp11a is the enzyme that converts cholesterol into pregnenolone.

Cyp17 (17,20lyase) is the enzyme that converts pregnenolone to dehydroepiandrosterone (DHEA).

3β-HSD is the enzyme that converts pregnenolone to progesterone and DHEA to androstenedione in the adrenal gland.

cAMP acts as a second messenger in cells and also increases testosterone synthesis and further increases StAR activity.

Cyp2r1 is the enzyme that converts vitamin D into its active form. The active form of vitamin D also acts as a hormone, a steroid hormone, and has a significantly positive effect on steroidogenesis.

Osteocalcin-deficient mice exhibit increased levels of luteinizing hormone (LH), however this is not enough to raise testosterone to adaquate levels, hence the lower testosterone levels. (6) LH is associated with higher testosterone as well as higher estrogen.

Circulating undercarboxylated osteocalcin is also positively correlated with free testosterone. (7)



Exercise
Osteocalcin also acts on muscle cells to promote energy availability and utilization and in this manner favors exercise capacity. Osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, and it's also mostly responsible for the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise. (8)



How to increase osteocalcin:

Vitamin D
Vitamin D, and mostly the active form of vitamin D, stimulate the synthesis of osteocalcin (1,25-(OH)2D3) in a dose dependent manner. (9, 10)



Vitamin K2
High intake of vitamin K results in a low proportion of undercarboxylated osteocalcin. Osteoblast releases inactive (undercarboxylized) osteocalcin, which is then activated (carboxylized) by vitamin K, which then undergoes decarboxylation in the resorption lacunae (osteoclast). This means the osteoclast also releases undercarboxylated osteocalcin, which is hormanally active. Vitamin K has been associated with enhanced bone mineral density, increased testosterone, enhanced insulin sensitivity and better glucose tolerance. The exact same benefits as undercarboxylized osteocalcin, meaning higher intake of vitamin K might not lead to lower undercarboxylated osteocalcin, as both he osteoblast and the osteoclast releases it into the circulation. It's possible that vitamin K increases total osteocalcin, and therefore the amount of undercarboxylated osteocalcin increase, despite that the ratio of undercarboxylated osteocalcin to carboxylated osteocalcin stay he same or decrease a bit.



Insulin & leptin
The osteoblast in bone contains insulin receptors, and requires insulin to active the receptors and result in an increase in osteocalcin. (11) A high fat diet result in a decrease in undercarboxylated osteocalcin and thus a decrease in insulin sensitivity. This could leads to insulin resistance, low/impaired bone turnover and increased fat mass. (12)

Leptin also positively increases osteocalcin, whereas high levels decrease it. (13, 14)



Magnesium

Osteocalcin mRNA is reduced in a magnesium deficiency, and therefore osteocalcin synthesis is reduced. (15) Also, magnesium ions induce significant increases in osteocalcin levels in human osteoblasts. (16)



Exercise
Acute exercise (especially aerobic exercise) appeared at least in part related to increased undercarboxylated osteocalcin levels. (17)



Lower cortisol

Chronic elevated cortisol leads to weight gain, insulin resistance, and diabetes, increased aromatase, degraded androgen receptors and increase risk of autoimmune disease, etc, and it also suppresses osteoblast function, including osteocalcin synthesis. (18)



Zinc

Zinc is known to aid in bone formation and zinc intake are positively associated with osteocalcin levels as zinc stimulates the osteoblast. (19) Just be sure to consume enough zinc rich foods and maybe take a supplement. 50mg a day would be a good starting dose.



Growth hormone
Osteoblasts have receptors for GH and these cells produce large amounts of IGF-I. IGF-I has positive effects on bone formation; firstly, it is known to stimulate the formation of osteocalcin, collagen, and noncollagenous matrix proteins by differentiated osteoblasts and secondly, it increases the number of functional osteoblasts by promoting osteoprogenitor cell replication. (20)

Let me know what you guys think...
 

JoeKool

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Hey man this looks like some cool info. Very few ppl know of leptin, the satiation hormone. And what you listed to take are all good base supplements. Thanks for this write up
 

haidut

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Osteocalcin, acts as a hormone and is able to increase testosterone, increase insulin and its sensitivity, as well as decrease fat mass by increasing energy expenditure.

Osteocalcin, (a.k.a. bone gamma-carboxyglutamic acid-containing protein (BGLAP)), is a noncollagenous protein hormone found in bone and dentin. Osteocalcin is secreted mainly by osteoblasts and a few other tissues, such as adipose tissue, and it was mainly thought to only aids in bone-building,

When the osteoblast releases osteocalcin, it's either in it's carboxylated or undercarboxylated form. The carboxylated form is when vjtamin K "activates" it so that it can aid in bone mineralization in the bone matrix. The undercarboxylated osteocalcin are released into the blood stream. Undercarboxylated are the hormonally active form of osteocalcin.

High levels (too high) of undercarboxylated osteocalcin are associated with:

  • high levels of adiponectin (better insulin sensitivity)
  • more insulin secretion (it stimulates the beta cells of the pancreas)
  • increased energy expenditure
  • lower fat mass
  • higher testosterone
  • impaired glucose metabolism (hyperinsulinemia and hypoglycemia) (1)
  • Soft tissue calcification (thats why you need vitamin K to carboxylate a fraction of osteocalcin to prevent negative effects)
Whereas too low levels of undercarboxylated osteocalcin is associated with:

  • hyperglycemia
  • hypoinsulinemia
  • insulin resistance
  • reduced energy expenditure
  • obesity
  • reduced testosterone levels
Both lower and higher total osteocalcin levels predicted increased all-cause mortality rates, with comparable associations for cardiovascular and noncardiovascular deaths. (2)



Testosterone
Undercarboxylated osteocalcin acts on the Leydig cells of the testis to stimulate testosterone biosynthesis via the bone-testis axis. The undercarboxylated osteocalcin binds to a G protein-coupled receptor (GPCR6A), which is expressed in the testis, and regulates StAR, Cyp11a, Cyp17 and 3β-HSD, cAMP and Cyp2r1 expression, through CREB as the transcriptional mediator which activates these enzymes. (3, 4, 5)

StAR are the rate limited enzyme that transports cholesterol from the outer mitochondria into the inner mitochondria of the Leydig cells to synthesize the precursor to all steroids, pregnenolone.

Cyp11a is the enzyme that converts cholesterol into pregnenolone.

Cyp17 (17,20lyase) is the enzyme that converts pregnenolone to dehydroepiandrosterone (DHEA).

3β-HSD is the enzyme that converts pregnenolone to progesterone and DHEA to androstenedione in the adrenal gland.

cAMP acts as a second messenger in cells and also increases testosterone synthesis and further increases StAR activity.

Cyp2r1 is the enzyme that converts vitamin D into its active form. The active form of vitamin D also acts as a hormone, a steroid hormone, and has a significantly positive effect on steroidogenesis.

Osteocalcin-deficient mice exhibit increased levels of luteinizing hormone (LH), however this is not enough to raise testosterone to adaquate levels, hence the lower testosterone levels. (6) LH is associated with higher testosterone as well as higher estrogen.

Circulating undercarboxylated osteocalcin is also positively correlated with free testosterone. (7)



Exercise
Osteocalcin also acts on muscle cells to promote energy availability and utilization and in this manner favors exercise capacity. Osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, and it's also mostly responsible for the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise. (8)



How to increase osteocalcin:

Vitamin D
Vitamin D, and mostly the active form of vitamin D, stimulate the synthesis of osteocalcin (1,25-(OH)2D3) in a dose dependent manner. (9, 10)



Vitamin K2
High intake of vitamin K results in a low proportion of undercarboxylated osteocalcin. Osteoblast releases inactive (undercarboxylized) osteocalcin, which is then activated (carboxylized) by vitamin K, which then undergoes decarboxylation in the resorption lacunae (osteoclast). This means the osteoclast also releases undercarboxylated osteocalcin, which is hormanally active. Vitamin K has been associated with enhanced bone mineral density, increased testosterone, enhanced insulin sensitivity and better glucose tolerance. The exact same benefits as undercarboxylized osteocalcin, meaning higher intake of vitamin K might not lead to lower undercarboxylated osteocalcin, as both he osteoblast and the osteoclast releases it into the circulation. It's possible that vitamin K increases total osteocalcin, and therefore the amount of undercarboxylated osteocalcin increase, despite that the ratio of undercarboxylated osteocalcin to carboxylated osteocalcin stay he same or decrease a bit.



Insulin & leptin
The osteoblast in bone contains insulin receptors, and requires insulin to active the receptors and result in an increase in osteocalcin. (11) A high fat diet result in a decrease in undercarboxylated osteocalcin and thus a decrease in insulin sensitivity. This could leads to insulin resistance, low/impaired bone turnover and increased fat mass. (12)

Leptin also positively increases osteocalcin, whereas high levels decrease it. (13, 14)



Magnesium

Osteocalcin mRNA is reduced in a magnesium deficiency, and therefore osteocalcin synthesis is reduced. (15) Also, magnesium ions induce significant increases in osteocalcin levels in human osteoblasts. (16)



Exercise
Acute exercise (especially aerobic exercise) appeared at least in part related to increased undercarboxylated osteocalcin levels. (17)



Lower cortisol

Chronic elevated cortisol leads to weight gain, insulin resistance, and diabetes, increased aromatase, degraded androgen receptors and increase risk of autoimmune disease, etc, and it also suppresses osteoblast function, including osteocalcin synthesis. (18)



Zinc

Zinc is known to aid in bone formation and zinc intake are positively associated with osteocalcin levels as zinc stimulates the osteoblast. (19) Just be sure to consume enough zinc rich foods and maybe take a supplement. 50mg a day would be a good starting dose.



Growth hormone
Osteoblasts have receptors for GH and these cells produce large amounts of IGF-I. IGF-I has positive effects on bone formation; firstly, it is known to stimulate the formation of osteocalcin, collagen, and noncollagenous matrix proteins by differentiated osteoblasts and secondly, it increases the number of functional osteoblasts by promoting osteoprogenitor cell replication. (20)

Let me know what you guys think...

We posted about this before, but thanks for gathering all of this info. I think it helps to have it all in one thread for those interested in learning more.
Vitamin K And D Reverse Muscle Aging, May Act Like Sports Doping Agents
 

Jon

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Colorado
Found a cool infographic to give a picture to your book lol it's very basic but nice to look at.

IMG_3129.JPG

Good stuff man.
 

BigChad

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Joined
Jun 28, 2019
Messages
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Osteocalcin, acts as a hormone and is able to increase testosterone, increase insulin and its sensitivity, as well as decrease fat mass by increasing energy expenditure.

Osteocalcin, (a.k.a. bone gamma-carboxyglutamic acid-containing protein (BGLAP)), is a noncollagenous protein hormone found in bone and dentin. Osteocalcin is secreted mainly by osteoblasts and a few other tissues, such as adipose tissue, and it was mainly thought to only aids in bone-building,

When the osteoblast releases osteocalcin, it's either in it's carboxylated or undercarboxylated form. The carboxylated form is when vjtamin K "activates" it so that it can aid in bone mineralization in the bone matrix. The undercarboxylated osteocalcin are released into the blood stream. Undercarboxylated are the hormonally active form of osteocalcin.

High levels (too high) of undercarboxylated osteocalcin are associated with:

  • high levels of adiponectin (better insulin sensitivity)
  • more insulin secretion (it stimulates the beta cells of the pancreas)
  • increased energy expenditure
  • lower fat mass
  • higher testosterone
  • impaired glucose metabolism (hyperinsulinemia and hypoglycemia) (1)
  • Soft tissue calcification (thats why you need vitamin K to carboxylate a fraction of osteocalcin to prevent negative effects)
Whereas too low levels of undercarboxylated osteocalcin is associated with:

  • hyperglycemia
  • hypoinsulinemia
  • insulin resistance
  • reduced energy expenditure
  • obesity
  • reduced testosterone levels
Both lower and higher total osteocalcin levels predicted increased all-cause mortality rates, with comparable associations for cardiovascular and noncardiovascular deaths. (2)



Testosterone
Undercarboxylated osteocalcin acts on the Leydig cells of the testis to stimulate testosterone biosynthesis via the bone-testis axis. The undercarboxylated osteocalcin binds to a G protein-coupled receptor (GPCR6A), which is expressed in the testis, and regulates StAR, Cyp11a, Cyp17 and 3β-HSD, cAMP and Cyp2r1 expression, through CREB as the transcriptional mediator which activates these enzymes. (3, 4, 5)

StAR are the rate limited enzyme that transports cholesterol from the outer mitochondria into the inner mitochondria of the Leydig cells to synthesize the precursor to all steroids, pregnenolone.

Cyp11a is the enzyme that converts cholesterol into pregnenolone.

Cyp17 (17,20lyase) is the enzyme that converts pregnenolone to dehydroepiandrosterone (DHEA).

3β-HSD is the enzyme that converts pregnenolone to progesterone and DHEA to androstenedione in the adrenal gland.

cAMP acts as a second messenger in cells and also increases testosterone synthesis and further increases StAR activity.

Cyp2r1 is the enzyme that converts vitamin D into its active form. The active form of vitamin D also acts as a hormone, a steroid hormone, and has a significantly positive effect on steroidogenesis.

Osteocalcin-deficient mice exhibit increased levels of luteinizing hormone (LH), however this is not enough to raise testosterone to adaquate levels, hence the lower testosterone levels. (6) LH is associated with higher testosterone as well as higher estrogen.

Circulating undercarboxylated osteocalcin is also positively correlated with free testosterone. (7)



Exercise
Osteocalcin also acts on muscle cells to promote energy availability and utilization and in this manner favors exercise capacity. Osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, and it's also mostly responsible for the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise. (8)



How to increase osteocalcin:

Vitamin D
Vitamin D, and mostly the active form of vitamin D, stimulate the synthesis of osteocalcin (1,25-(OH)2D3) in a dose dependent manner. (9, 10)



Vitamin K2
High intake of vitamin K results in a low proportion of undercarboxylated osteocalcin. Osteoblast releases inactive (undercarboxylized) osteocalcin, which is then activated (carboxylized) by vitamin K, which then undergoes decarboxylation in the resorption lacunae (osteoclast). This means the osteoclast also releases undercarboxylated osteocalcin, which is hormanally active. Vitamin K has been associated with enhanced bone mineral density, increased testosterone, enhanced insulin sensitivity and better glucose tolerance. The exact same benefits as undercarboxylized osteocalcin, meaning higher intake of vitamin K might not lead to lower undercarboxylated osteocalcin, as both he osteoblast and the osteoclast releases it into the circulation. It's possible that vitamin K increases total osteocalcin, and therefore the amount of undercarboxylated osteocalcin increase, despite that the ratio of undercarboxylated osteocalcin to carboxylated osteocalcin stay he same or decrease a bit.



Insulin & leptin
The osteoblast in bone contains insulin receptors, and requires insulin to active the receptors and result in an increase in osteocalcin. (11) A high fat diet result in a decrease in undercarboxylated osteocalcin and thus a decrease in insulin sensitivity. This could leads to insulin resistance, low/impaired bone turnover and increased fat mass. (12)

Leptin also positively increases osteocalcin, whereas high levels decrease it. (13, 14)



Magnesium

Osteocalcin mRNA is reduced in a magnesium deficiency, and therefore osteocalcin synthesis is reduced. (15) Also, magnesium ions induce significant increases in osteocalcin levels in human osteoblasts. (16)



Exercise
Acute exercise (especially aerobic exercise) appeared at least in part related to increased undercarboxylated osteocalcin levels. (17)



Lower cortisol

Chronic elevated cortisol leads to weight gain, insulin resistance, and diabetes, increased aromatase, degraded androgen receptors and increase risk of autoimmune disease, etc, and it also suppresses osteoblast function, including osteocalcin synthesis. (18)



Zinc

Zinc is known to aid in bone formation and zinc intake are positively associated with osteocalcin levels as zinc stimulates the osteoblast. (19) Just be sure to consume enough zinc rich foods and maybe take a supplement. 50mg a day would be a good starting dose.



Growth hormone
Osteoblasts have receptors for GH and these cells produce large amounts of IGF-I. IGF-I has positive effects on bone formation; firstly, it is known to stimulate the formation of osteocalcin, collagen, and noncollagenous matrix proteins by differentiated osteoblasts and secondly, it increases the number of functional osteoblasts by promoting osteoprogenitor cell replication. (20)

Let me know what you guys think...

Have high doses of mk4 ever been tested as it relates to osteocalcin? Based on this, if vitamin k decreases undercarboxylated osteocalcin this would mean high dose vitamin k causes increased fat gain among other effects. So based on this perhaps it's better to limit oral K intake? Or, drastically increase D intake if taking K?
 

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