The Relationship Between Zinc, IGF-I, and Osteo
The body does not need a lot of zinc but it closely regulates its zinc levels. One of the symptoms of zinc deficiency is impaired bone growth. Recent evidences suggest that zinc may even be more important for bone mineralization than calcium even though it makes up much less of the mineral content of bones. So, how does zinc improve bone health? What is the link between zinc and insulin-like growth factor? How does zinc influence the bone cells known as osteoblasts and osteoclasts? Read on to discover how zinc lowers the risk of bone fractures in osteoporosis.
by Brad Chase
Zinc is a trace but essential mineral in humans. Along with iron, it is the only other metal that is found in all classes of enzymes.
Zinc is not only important for enzymes but also for proteins and amino acid syntheses. It is involved in learning, memory formation, cellular signaling, gene expression and the metabolism of DNA and RNA.
The body keeps a store of 2 – 4 g of zinc most of which are found in the prostate gland, eye, brain, kidney, liver, muscles and bones.
The recommended dietary allowance for zinc is 8 mg/kg for women and 13 mg/kg for men. Excellent dietary sources of zinc include read meat, liver, beef, oyster and lobster. Good levels of zinc can also be found in whole grains, nuts, blackcurrant and seeds of sunflower, pumpkin, sesame, celery, poppy, alfalfa and mustard.
Zinc can also be obtained from diet through zinc-enriched foods especially nutrient-fortified cereals.
Zinc supplements are also available although the bioavailability of zinc varies widely between supplements. Studies find zinc sulfate to be better than zinc oxide and zinc carbonate.
Although most people meet the daily recommended dietary allowance for zinc, zinc deficiency is still common. This is because a number of chronic conditions can lead to low zinc levels.
Symptoms of zinc deficiency include impaired immunity, slow growth, hair loss, skin lesions, impotence, delayed sexual maturation, diarrhea, impaired appetite, cognitive decline and impaired metabolism of carbohydrates.
Zinc deficiency is most common among the elderly as well as among children especially those in developing countries.
Although calcium is the mineral most associated with bone formation, zinc is also found in the bones.
Although it makes up a small percentage of the bone, zinc is needed to form hydroxylapatite which is a naturally occurring crystalline calcium complex. Hydroxylapatite crystals form the bulk of bones and teeth.
Modified forms of hydroxyapatite actually account for about half of the weight of the bone.
Therefore, zinc is important to the proper mineralization of bones by contributing to its bone mass.
Zinc can also improve bone health indirectly by other means. For example, zinc promotes wound healing and enhances the functions of the immune system.
Therefore, zinc supplementation can help speed up the healing of fractured bones and ensure that the immune system protects bones from infections and toxins.
However, the major contributions of zinc to bone health are through its regulation of bone formation and bone resorption as well as its ability to affect the level of insulin-like growth factor.
Insulin-like growth factor (IGF-1) is released from the liver. It is transported to different tissues through the blood. This growth factor acts like a hormone and is required for different aspects of growth and maturation.
Since the bone is really a tissue, it is also affected by the level of IGF-1. At the bones, IGF-1 regulates bone homeostasis.
This means that it influences calcium balance in bones and, therefore, bone formation and re-absorption.
This regulation means that low blood levels of IGF-1 soon leads to loss of calcium from bones and increased risk of osteoporosis.
Studies have shown that zinc levels are positively correlated with IGF-1 levels. The evidence suggests that zinc stimulates the release of IGF-1. In fact, the impaired growth and poor bone health associated with zinc deficiency is believed to be due to low levels of circulating IGF-1.
Because zinc deficiency is common among the elderly, there is reason to believe that falling levels of IGF-1 also contributes to the higher risk of osteoporotic bone fractures among old people.
The contribution of IGF-1 to bone health also extends beyond bones. Because IGF-1 is used to drive muscle growth and maintain muscle strength, it can help prevent atrophy in the muscles surrounding the bones of the limbs.
Muscle loss occurs as we age and it can also be traced to falling IGF-1 levels. Therefore, when zinc stimulates the release of IGF-1, it strengthens the muscles and reduces the chance of falls that can lead to bone fractures in the elderly.
Another major contribution of zinc to bone health is its ability to stimulate osteoblasts and inhibit osteoclasts.
Osteoblasts and osteoclasts are bone cells. However, osteoblasts are needed for bone formation while osteoclasts are responsible for bone resorption.
Osteoblasts produce the protein, osteocalcin which is responsible for fixing calcium into bone matrix. When there is a healthy population of functional osteoblasts, bone mineral density increases. On the other hand, osteoclasts regulate bone resorption. This means that they promote the breakdown of bone and its reabsorption.
Therefore, osteoblasts are bone builders while osteoclasts are bone breakers.
By promoting the activities of osteoblasts and reducing the activity of osteoclasts, zinc produces a net bone-building effect. This increases bone mineral density and reduces the risk of osteoporotic bone fractures.
Because most studies on osteoporosis determine the effectiveness of treatments on osteoporotic old women, the researchers of a 2004 study published in The American Journal of Clinical Nutrition tried to determine whether the same can be applied to elderly men.
For this study (Rancho Bernado Study), 392 men aged 45 – 92 years were involved. Over a period of 4 years, the researchers collected data on the men’s diets, plasma zinc levels and bone mineral densities.
Their results showed that plasma zinc levels were determined by dietary zinc intakes.
In addition, zinc levels were lowest in men suffering from osteoporosis. These men also had the least bone mineral densities.
A similar study published in the Iranian Journal of Public Health in 2007 involved 600 men aged 20 – 69 years.
By measuring serum zinc levels, body mass indices and bone mineral densities, the researchers determined that zinc level was an accurate measure to predict bone mineral density in men over 40 years. In addition, they also found that osteoporosis was more common in men suffering zinc deficiency.
In a letter to the editor of BMJ published in 2005, a British researcher Ellen C.G. Grant MD corrected the conclusions of another researcher who discussed the relevant treatment choices of osteoporosis for postmenopausal women.
The author stated that contrary to popular belief, the evidence from past studies and the study in contention showed that the root cause of osteoporosis among postmenopausal women was not calcium deficiency or falling estrogen levels.
Rather, she contended that low serum bone alkaline phosphatase activity is responsible for the changes that cause osteoporosis.
Alkaline phosphatase is an enzyme that contributes to bone formation. When the activity of this enzyme is diminished, calcium is stripped from the bones.
However, the reduced activity of alkaline phosphatase is actually due to low serum levels of 3 key nutrients: zinc, magnesium and manganese.
The author not only condemned high-dose calcium supplementation in osteoporosis therapy but also hormone replacement therapy.
Hormone replacement therapy has been shown to lower blood levels of zinc, magnesium and alkaline phosphatase. In addition, studies show that people placed on hormone replacement therapy lose more zinc through urinary excretion.
The author backed up her assertions with the published observation that bone fractures among women aged 35 – 65 years were at the highest in countries where hormone replacement therapies are commonly prescribed.
These insights show that instead of giving postmenopausal women calcium and estrogen to prevent and treat osteoporosis, zinc and magnesium should be given to enhance the activity of alkaline phosphatase.
Although zinc is known to promote the activity and increase the population of osteoblasts (bone-forming cells), the exact mechanism by which it does that is not fully understood. However, a 2012 study published in the Journal of Translational Medicine provided a useful insight into the genetic mechanism involved.
The researchers found that osteoblasts and adipocytes (fat cells) are derived from the same stem cells.
In addition, they also found that osteoporosis results when the progenitor stem cells differentiate into adipocytes rather than osteoblasts.
By taking their investigation to the genetic level, they were able to determine that a zinc finger protein (Zfp467) was responsible for determining whether the parent stem cell became an osteoblast or an adipocyte.
This information is important because it can help drug scientists design better osteoporosis medications that target this zinc protein.
By encouraging Zfp467 to make osteoblasts (rather than fat cells) from this shared parent stem cell, bone mineral density can be increased and the risk of osteoporosis reduced.
A 1998 study published in The American Journal of Clinical Nutrition investigated the effects of common nutrients in the diet on insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding proteins (IGFBP).
By determining the nutrients in the diets of 119 postmenopausal women over a period of 2 years and comparing the levels of IGF-1 and IGFBP in these women, the researchers found out that zinc was the only nutrient that determined IGF-1 levels in the body.
From their results, they saw that low zinc intake was linked to low serum levels of IGF-1 in healthy postmenopausal women.
In addition, they found that protein intake did not affect IGF-1 level even though protein foods are importance sources of zinc.
A 2009 study published in The Journal of Nutrition, Health and Aging also determined the effects of zinc on IGF-1 levels in a community of the elderly.
The researchers believed that proteins can raise IGF-1 levels and reported the low intake of protein among the elderly as being partly responsible for the development of osteoporosis in that population.
The researchers, therefore, gave daily oral protein supplements to 61 hospitalized old people aged 66 – 106 years. During the 4-week period of the trial, they gave some of these participants 30 mg/day of zinc while the rest received placebo.
The results of the study showed that IGF-1 levels rose in all participants due to the protein supplement.
However, the rise was faster with those who received zinc. As early as the first week of the trial, the zinc group had double the IGF-1 level of the control group.
In addition, the zinc group experienced significantly lower level of serum bone resorption marker.
This study shows that zinc supplementation improves IGF-1 response to protein diet and should be used to prevent bone breakdown.
A 2010 study published in the journal, Molecular and Cellular Biochemistry outlined the different links between zinc and bone health.
The authors provided the following summary from their findings as well as past studies on the subject.
The researchers found that zinc compounds can stimulate bone formation. The two compounds identified were zinc acexamate and beta-alanyl-L-histidinato zinc or AHZ.
AHZ was found to stimulate bone formation a lot more than the more common zinc supplement, zinc sulfate.
The authors pointed out that AHZ or zinc acexamate can reverse bone loss caused by aging; skeletal unloading; aluminum bone toxicity; deficiencies of estrogen, calcium and vitamin D; arthritis; diabetes; and healing fractures.
The breadth of zinc’s effect on bone health highlights the growing belief that it should be one of the recommended primary supplements given to people suffering from osteoporosis.
It also means that zinc addresses the root cause of osteoporosis and should replace calcium as a first-line nutritional supplement for osteoporosis.
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