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Bone-Building Ingredients

By Yousry Naguib, Ph.D.

March 2004—NUTRACEUTICALS WORLD MAGAZINE

Adequate intakes of nutrients composing the bone matrix and regulating bone metabolism appear necessary to maintain bone health and prevent bone disorders and diseases.

A startling image of the skeleton is often created when we think of bones. The importance of bones providing the framework structure in the body is clear, but their nature of complexity is not always fully appreciated. Bone is in fact a living tissue that is constantly being renewed and removed through the bone turnover cycle. Like other body tissues, bones are vulnerable to disorders and diseases, the most prevalent ones being osteoporosis and arthritis.

Bone is a specialized form of dense connective tissue, which give the body’s skeleton the necessary rigidity to function as attachment and lever for muscles, and supports the body against gravity.

Bone is composed primarily of the minerals calcium and phosphorus, as well as the protein collagen. It is the calcium and phosphorus component of bone that makes it hard and rigid. The organic component of the bone matrix comprises 40% of the dry weight of bone, of which 90% is collagen and 10% proteoglycans and proteins. The inorganic components of the bone matrix, 60% of dry weight bone, is composed of calcium phosphate and calcium hydroxyapatite, which are responsible for the compression strength of bone.

Bone Diseases & Conditions

According to the National Institutes of Health (NIH), Bethesda, MD, an estimated 28 million Americans have low bone mass, which is an early warning sign of osteoporosis. Another 10 million Americans, 80% of whom are women, have osteoporosis.

Osteoporosis is a bone disease in which the bone becomes weaker and more likely to fracture. It is considered a women’s disease, but the prevalence in men also increases with age. Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures of the hip, spine and wrist.

The disease can occur due to estrogen deficiency in women, or as an age-related bone loss in both women and men. Some medications, such as glucocorticords or some anti-convulsions, may also have a negative effect on bone density and increase the chances for osteoporosis.

Osteoporosis is manifested clinically as fractures and on non-invasive imaging tests as low bone density. Prevention of osteoporosis is the most cost effective means of managing this disease, which is why it is crucial to have bone mass (bone mineral density) measured.

A bone mineral density (BMD) test can help diagnose osteoporosis. BMD tests are safe, painless and non-invasive; they involve measuring bone density in the spine, hip and/or wrist, which are the most common sites of fractures due to osteoporosis. Several different kinds of machines can do BMD testing. The most common methods incorporate low-dose x-rays, such as DXA (Dual Energy X-Ray Absorptiometry), which measures the spine, hip or total body.

BMD testing is recommended for all women aged 65 and older, and women under 65 with additional risk factors, such as estrogen deficiency and hyper-parathyroidism.

Arthritis comes from the Greek word “arthron” meaning a joint. Arthritis affects nearly 40 million Americans, roughly one American in six; and in 2020 an estimated 60 million Americans will have some form of the disease. The most common forms of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA).

OA accounts for more than half of all arthritis cases; an estimated 25 million Americans—mostly women over 45—have OA. OA is a degenerative disorder in which the cartilage between the joints wears away. Normally, cartilage provides a cushion to help bones glide over one another and to absorb shock from physical movement, such as running. When the cartilage breaks down and wears away, the bones rub together causing pain and swelling.

OA is usually age-related and most often occurs at the ends of the fingers and thumbs, neck, lower back, knees and hips. OA is also one of the most frequent causes of physical disability among adults.

RA (from the Latin rheumatisms catarrh) is an inflammatory autoimmune disease that affects the whole body, primarily the joints. It is believed that RA occurs when the body’s immune system turns against itself and starts to damage joint tissues. RA causes inflammation and deformity of the joints. According to the Arthritis Foundation, RA affects two million Americans and usually strikes in middle age (35 to 50 years old). Women are three times more likely than men to develop the disease. RA can begin very gradually or it can strike without warning. The first symptoms are pain, swelling and stiffness in the joints. The most commonly involved joints include hands, feet, wrists, elbows and ankles.

RA commonly affects joints on both sides of the body at the same time and can involve the small joints found in the fingers, wrists, ankles and toes as well as the shoulders and the knees.

Minerals

Calcium: Calcium is an essential nutrient that is required structurally in bones and teeth as an intracellular regulator and as a cofactor for numerous proteins and enzymes. Consumption of adequate dietary calcium reduces the risk of several disorders, the most studied of which is osteoporosis.

A low calcium intake has been postulated to be an important predictor of fractures because bones are largely composed of calcium phosphate and a combination of calcium phosphate and calcium hydroxide (called hydroxyapatite). Calcium supplements usually include other nutrients, including vitamin D, magnesium and riboflavin.

There are many forms of calcium, such as calcium carbonate, calcium citrate, calcium gluconate, oyster shell calcium, scallop shell calcium, eggshell calcium, milk products and coral calcium, and they all have varying degrees of bioavailability and effectiveness. Calcium carbonate is the most widely used and least expensive form of calcium. When taken with meals, calcium carbonate has been shown to be as absorbable (39%) as other forms of calcium, including calcium acetate (32%), calcium lactate (32%), milk (31%), calcium citrate (30%) and calcium gluconate (27%) (1).

In a recent clinical study, both calcium carbonate and calcium citrate showed equivalent bioavailability (2). However, earlier studies have indicated that calcium citrate is better absorbed than calcium carbonate by approximately 22-27%, either on an empty stomach or co-administered with meals (3).

Research published in 1991 on calcium therapy for preventing osteoporosis indicated that while calcium supplementation does not halt the development of osteoporosis, it significantly slows bone loss in postmenopausal women (4). Elderly women with decreased fractional calcium absorption (the fraction of calcium absorbed from the gut) and low calcium intake are at greater risk for hip fracture (5).

Active Absorbable Algal Calcium (AAA Ca). AAA Ca is oyster shell heated under reduced pressure to which a heated seaweed powder has been added. The original oyster shell contains calcium carbonate and the oyster shell heated in vacuo contains both calcium carbonate and calcium oxide. AAA Ca has been reported to be absorbed from the intestine more efficiently than calcium carbonate.

Its benefit on osteoporosis was demonstrated in a randomized, double-blind study. Fifty-eight women with a mean age of 80 years were divided into three groups: group A received 900 mg per day AAA Ca, group B 900 mg per day calcium carbonate and group C placebo. All groups were given a regular diet containing approximately 600 mg calcium per day for 24 months. From the 6th to the 24th month, group A, and not B and C, showed a significant increase in lumbar spine BMD. After 12 months, the serum parathyroid hormone was lower in group A than in groups B and C. AAA Ca appeared to be more effective in increasing BMD than calcium carbonate containing the same amount of elemental calcium (6).

In a follow-up study, the researchers reported that, in addition to increasing BMD and preventing fracture, AAA Ca, but not calcium carbonate, appeared to inhibit new occurrence of vertebral deformity and fracture, and to decrease body fat content (7).

Chicken Eggshell Powder: Supplementation with chicken eggshell powder may increase BMD of the hip in late postmenopausal women in 12 months. Eighty-five healthy women aged 50 to 70 years, who were at least five years postmenopausal, were given either chicken eggshell powder, calcium carbonate or a placebo for 12 months—both calcium sources were provided in combination with minerals and vitamins, including magnesium, cholecalciferol and phylloquinone. Only the eggshell group showed a significant increase in the BMD of the femoral neck. This increase coincided with significant decreases in markers of bone resorption and formation (8).

Coral Calcium: The majority of coral calcium products are made of calcium carbonate from coral reefs. Coral calcium has been shown to be an optimal source of calcium and magnesium in the desired ratio of two to one.

In a small cross-over clinical trial, 12 healthy adult volunteers ingested either coral-added crackers (providing 525 mg calcium) or calcium carbonate-added crackers. Urinary calcium excretion was significantly greater after ingestion of coral added-crackers than calcium carbonate-added crackers. These limited data suggest that the calcium of coral origin was better absorbed from the intestine than calcium from calcium carbonate (9).

Boron: Boron is effective in helping bones retain calcium. The herb stinging nettle contains 47 parts per million of boron. This means that a 100-gram serving of stinging nettle could contain more than the recommended amount of boron.

Vitamins

Vitamin D: Vitamin D is a primary regulator of calcium absorption in the body. It is formed in the skin after exposure to ultraviolet radiation and is also absorbed from the diet. It is converted in the liver into 25-hydroxy-vitamin D, and again in the kidney to 1,25-dihydroxy-vitamin D. Adequate vitamin D and calcium intake is the cornerstone of osteoporosis prevention and treatment.

Combined calcium (500 mg of elemental calcium as carbonate) and vitamin D (400 IU) daily supplementation was found to significantly increase bone mineral density in elderly women with vitamin D deficiency (10).

In an earlier study, daily supplementation with 500 mg calcium and 700 IU vitamin D for three years was shown to moderately reduce bone loss and fracture incidence in 389 men and women over the age of 65 years (11).

Vitamin D intake between 500 and 800 IU daily, with or without calcium supplementation, has been shown to increase BMD in women with a mean age of approximately 63 years. In women older than 65, there is even more benefit with vitamin D intakes of between 800 and 900 IU daily and 1200-1300 mg of calcium daily, resulting in increased bone density, decreased bone turnover and decreased non-vertebral fractures (12).

In a recent prospective analysis involving 72,337 postmenopausal women, researchers at Harvard Medical School found that women who consumed more than 12.5 mcg vitamin D per day from food plus supplements had a 37% lower risk of hip fracture than did women who consumed less than 3.5 mcg per day vitamin D. Both total calcium intake and milk consumption were not associated with a lower risk of hip fracture. The study concluded that adequate vitamin D intake is associated with a lower risk of hip fracture in postmenopausal women. Neither milk nor a high calcium diet appeared to reduce risk of hip fracture (13).

Vitamin K: Low dietary vitamin K intake has been associated with an increased risk of hip fracture in men and women. This was demonstrated in a study conducted at Tufts University, where researchers examined the association of the dietary and supplemental intakes of vitamin K and BMD of the hip and spine in 1112 men and 1479 women aged 29-86 years. Women with lowest vitamin K intakes had significantly lower BMD at the femoral neck and spine than did those with the highest vitamin K intakes. However, no significant association was found between dietary vitamin K intakes and BMD in men (14).

Vitamin K, co-administered with vitamin D and minerals, was also found to retard bone loss in postmenopausal women. In a randomized, double-blind, placebo-controlled study, 155 healthy postmenopausal women between 50 and 60 yeard of age received a daily supplement containing either placebo, or calcium, magnesium, zinc and vitamin D (MD group), or the same formulation with additional vitamin K (MDK group). After three years treatment, the group receiving the supplement containing additional vitamin K showed reduced bone loss of the femoral neck (15).

Other Nutrients

Phytoestrogens: Phytoestrogens, estrogen-like natural compounds known as isoflavones, may also play a role in countering bone loss. Phytoestrogen isoflavones therapy has been proposed as a natural alternative to hormone replacement therapy (HRT), which also has a beneficial effect on bone.

In a recent double-blind, randomized, placebo-controlled trial, 177 women aged 49-65 years received a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A, 16 mg formononetin, 1 mg genistein and 0.5 mg daidzein, or placebo for one year. Loss of lumbar spine bone mineral content and BMD was significantly lower in the women taking the isoflavone supplement than in those taking the placebo. The study suggested that isoflavones have a potentially protective effect on the lumbar spine in women (16).

The association between usual and un-supplemented dietary isoflavone intake and BMD was evaluated in 208 postmenopausal women. Information on intake of isoflavones over a year was assessed with a standard questionnaire. Women with the highest daily intake of dietary isoflavones had lower concentration of bone resorption (removal) markers, and greater bone density at the spine. The data suggested that dietary isoflavone consumption may also be protective against bone loss in postmenopausal women (17).

In another recent study, 23 healthy postmenopausal women were randomly assigned to receive either 62 mg isoflavones or placebo daily for four weeks. Both excretion of bone loss markers, and total serum cholesterol and LDL-cholesterol (bad cholesterol) were reduced significantly in the isoflavones group. The study concluded that soy isoflavones supplementation may reduce the risk of postmenopausal osteoporosis and cardiovascular diseases in women (18).

Glucosamine & Chondroitin: The top supplement ingredient for joint problems is still glucosamine sulfate (GS), a building block needed for the synthesis and repair of joint cartilage. Chondroitin sulfate (CS) is also an important component of the body’s natural building blocks found in the proteoglycans of cartilage. CS is a glycosaminoglycan, a polymeric material consisting of repeating glucuronic acid and N-acetylgalactosamine units. Glucosamine on the other hand acts as the building block for the biosynthesis of glycosaminoglycans needed for the formation of proteoglycans , which are important constituents of cartilage.

Both glucosamine and chondroitin are made from animal sources: Glucosamine sulfate is derived from chitin, a tissue found in shellfish; and chondroitin comes from the cartilage of sharks, cows and pigs.

Glucosamine sulfate not only relieves arthritis symptoms but also helps the body repair damaged joints (19).

A three-year double-blind, randomized, controlled clinical trial examined the effect of glucosamine sulfate on preventing joint space narrowing, a measure of progression of osteoarthritis, in 212 patients older than 50 with mild to moderate knee osteoarthritis. Patients took either 1500 mg/day of glucosamine sulfate or placebo over three years. X-ray radiographs of the knee showed that the average mean joint space loss was 0.31 mm in the placebo group and 0.07 mm in the treatment group (20).

A 16-week double-blind study conducted by the U.S. Navy on 34 males with chronic pain and radiographic degenerative disease of the knee found that patients who took the therapeutic combination of chondroitin sulfate (1,200mg/day), glucosamine hydrochloride (1,500mg/day) and manganese ascorbate (226mg/day) experienced significant relief of knee pain but no improvement in function (21). Most manufacturers recommend 500 milligrams of glucosamine and 400 milligrams of chondroitin three times daily.

Type-II Collagen: There are several types of collagen; the main ones are designated Type-I, Type-II and Type-III. Type-II collagen is found predominantly in articular cartilage and is sold in dietary supplements, such as Biocell Collagen-II (hydrolyzed collagen type II protein) and UC-II (not hydrolyzed). In a recent study, researchers found that 39% of 54 RA patients treated orally with un-denatured (not hydrolyzed) Type-II collagen demonstrated significant improvement, while only 19% of 57 RA patients taking placebo showed improvement (22).

Hyaluronic Acid (HA): HA is a polysaccharide composed of repeating units of N-acetyl-glucosamine and D-glucuronic acid. In humans, HA is found in the soft connective tissue, and the synovial joint fluid (the fluid secreted by the lining of the joint to nourish and lubricate the joint).

In OA, the concentration of HA is decreased in both the cartilage and synovial fluid. In 1997, the FDA approved HA for the treatment of OA of the knee. Clinical studies have shown that intra-articular injections of HA produce rapid pain relief and improved mobility in OA subjects (23).

One commercial source of HA is rooster combs (Injuv™) and another important source includes microorganisms, through a fermentation process.

References

1. Sheikh MS et al. “Gastrointestinal absorption of calcium from milk and calcium salts.” New England J Med 1987;317:532.

2. Heaney RP et al. “Absorbability and cost effectiveness in calcium supplementation.” J Am Coll Nutr 2001;20:239.

3. Sakhaee K et al. “Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate.” Am J Ther 1999;6:313.

4. Dawson-Hughes B. “Calcium supplementation and bone loss: A review of controlled clinical trials.” Am J Clin Nutr 1991;54:274S.

5. Ensrud KE et al. “Low fractional calcium absorption increases the risk for hip fracture in women with low calcium intake.” Study of Osteoporotic Fractures Research Group. Ann Intern Med 2000 7;132:345.

6. Fujita T et al. “Heated oyster shell-seaweed calcium (AAA Ca) on osteoporosis.” Calcif Tissue Int 1996;58:226.

7. Fujita T et al. “Reappraisal of Katsuragi calcium study, a prospective, double-blind, placebo-controlled study of the effect of active absorbable algal calcium (AAACa) on vertebral deformity and fracture.” J Bone Miner Metab 2004;22:32.

8. Schaafsma A et al. “Positive effects of a chicken eggshell powder-enriched vitamin-mineral supplement on femoral neck bone mineral density in healthy late postmenopausal Dutch women.” Br J Nutr 2002; 87:267.

9. Ishitani K et al. “Calcium absorption from the ingestion of coral-derived calcium by humans.” J Nutr Sci Vitaminol (Tokyo) 1999;45:509.

10. Grados F et al. “Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency.” Joint Bone Spine. 2003;.70:203.

11. O’Brien KO. “Combined calcium and vitamin D supplementation reduces bone loss and fracture incidence in older men and women.” Nutr Rev 1998;56:148.

12. Malabanan AO, Holick MF. “Vitamin D and bone health in postmenopausal women.” J Women’s Health (Larchmt) 2003;12:151.

13. Feskanich D, Willett WC, Colditz GA. “Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women.” Am J Clin Nutr 2003;77:504.

14. Booth SL et al. “Vitamin K intake and bone mineral density in women and men.” Am J Clin Nutr 2003;77:512.

15. Braam LA et al. “Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age.” Calcif Tissue Int 2003;73:21.

16. Atkinson C et al. “The effects of phytoestrogen isoflavones on bone density in women.” Am J Clin Nutr 2004;79:326.

17. Kritz-Silverstein D, Goodman-Gruen DL. “Usual dietary isoflavone intake, bone mineral density, and bone metabolism in postmenopausal women.” J Womens Health Gend Based Med 2002;11:69.

18. Uesugi T. et al. “Beneficial effects of soybean isoflavones supplementation on bone metabolism and serum lipids in postmenopausal Japanese women: A four-week study.” J Am Coll Nutr 2002;21:97.

19. Phoon S, Manolios. “N. Glucosamine: A nutraceutical in osteoarthritis.” Aust Fam Physician 2002;31:539.

20. Reginster JY et al. “Long-term effects of glucosamine on osteoarthritis progression: A randomized, placebo-controlled clinical trial.” Lancet 2001;357:251.

21. Leffler et al. “Glucosamine, chondroitin, and manganese ascorbate for degenerative disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study.” Mil Med 1999;164:85.

22. Barnett et al. “Treatment of Rheumatoid arthritis with oral type-II collagen.” Arthritis Rheum 1998;141:290.

23. Altman RD et al. “Intra-articular sodium hyaluronate in the treatment of patients with OA of the knee.” J Rheumatol 1998;25:2203.

 

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