February 16, 2012
Bone Health Research Highlights
Bone health is a cradle-to-grave issue. According to the National Institutes of Health (NIH), one of the main causes behind osteoporosis, the "silent disease" afflicting more than 40 million Americans with weakened bones, is inadequate optimal bone growth in childhood and adolescence. As a result, bones don't reach ideal peak bone mass. A consumer education piece developed by NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) said: "The bone mass attained in childhood and adolescence is an important determinant of lifelong skeletal health. The health habits your kids are forming now can make, or literally break, their bones as they age."
Consisting of collagen and crystals of calcium phosphate mineral, the salad days of bones' life cycle come early. Cells called osteoclasts and osteoblasts are also part of the composition and are responsible for bone remodeling, where osteoclasts remove old bone (bone resorption) and osteoblasts build new bone (bone formation). Until our early 20s, bone formation outpaces bone resorption. Bone mass may remain stable or decrease slightly for yearsthat's partly due to diet and physical activityuntil an age-related decline begins sometime after midlife.
According to NIH, environmental factors can determine anywhere from 10 percent to 50 percent of bone mass. The natural products industry has a number of options to help Americans of all ages improve their chances for a fracture-free future.
Next: Nutraceutical Ingredients
Calcium still ranks as one of the top bone health ingredients. According to SPINS, a market research and consulting firm for the natural products industry, calcium supplements supporting bone health earned $30.8 million in the natural channel for the 52 weeks ending Dec. 24, 2011. The skeleton is essentially a calcium and phosphorous warehouse. "When these elements are in short supply, the regulating hormones take them out of the bone to serve vital functions in other systems of the body," according to "Bone Health and Osteoporosis: A Report of the Surgeon General" (surgeongeneral.gov). "However, too many withdrawals weaken the bone and can lead to the most-common bone disorder, fractures." Phosphorous and calcium levels in the body must be balanced. If there's too much of the latter, the body will take away calcium from bones.
As for collagen, a French study featuring ovariectomized C3H mice of different ages fed a diet including hydrolyzed collagen revealed a reduction in bone loss via an increase in the diameter of the cortical areas of femurs.1 Collagen also works well in tandem with calcium. In a human study presented at the American Society for Bone and Mineral Research's annual meeting last fall, a calcium collagen chelate (as KoACT®, from AIDP) was shown to increase bone mineral density in total body DXA scans after three months of intake.2 When total body bone mineral density (BMD) was analyzed, the control group showed an average 1.2-percent decline from baseline, while the KoACT group showed an average 1.0-percent baseline increase.
Recent studies have illustrated the benefits of pairing vitamin Dretail's biggest moneymaker, according to SPINSwith calcium. Researchers at Australian Catholic University examined 20 pairs of peripubertal female identical twins, aged 9 to 13 years, who were randomly assigned to receive either 800 mg/d of calcium and 400 IU/d of vitamin D3, or a matched placebo.3 After six months, daily supplementation revealed, "greater gains in trabecular density, trabecular area, and strength strain index at the 4-percent of distal tibial and radial sites compared with the placebo group (p=0.001)." In another trial out of Greece, daily consumption of dairy products fortified with vitamin D3 and calcium by 40 post-menopausal women over 30 months yielded "favorable changes in several bone metabolism and bone mass indices and in counterbalancing seasonal variations in hormonal and biochemical molecules."4
A multi-pronged attack, one that goes beyond vitamin D and calcium, to bone health is advisable, according to a study from American University in Beirut.5 "Deficiencies in vitamin B, along with the consequent elevated homocysteine level, are associated with bone loss, decreased bone strength, and increased risk of fracture," according to researchers Hala Ahmadieh and Asma Arabi. "Deficiencies in vitamins C, E and K are also associated with compromised bone health; this effect may be modified by smoking, estrogen use or hormonal therapy after menopause, calcium intake and vitamin D."
Vitamins C and E have also shown potential in bone health. Researchers in Malaysia concluded after four months of giving normal male rats 60 mg/kg of alpha-tocopherol or gamma-tocotrienol that the latter improved, "all the parameters of bone biomechanical strength."6 A four-year study from Tufts University of 874 men and women (mean age 75) showed vitamin C could play a role in protecting the bone health of older men.7 Specifically, among male nonsmokers, total vitamin C intake (8.05 mug/d) was positively associated with femoral neck BMD.
What makes vitamin K useful in bone health combination formulas is that vitamin K2 activates the matrix GLA proteins responsible for removing circulating calcium from the arteries and binding it to the bone matrix. A Spanish cross-sectional analysis of 365 elderly men and women, 200 of whom were also included in a two-year longitudinal follow-up study, not only revealed, "a high dietary vitamin K intake [over 334 mcg for men; over 300 mcg for women] was associated with superior bone properties," but that the increased intake was, "significantly related to lower losses of bone mineral density and smaller increases in the porosity and elasticity attributed to aging."8
Next page: Soy, protein, magnesium, Quercetin and Cissus quadrangularis.
Soy contains a bevy of bone-beneficial elements, including the isoflavones daidzein and genistein. Five-week-old male mice given a diet containing 0.08-percent pure daidzein or genistein exhibited positive effects on bone formation after four weeks, Japanese researchers concluded.9 According to an Italian study, genistein stimulates osteoblast and inhibits osteoclast function, mainly through the osteoprotegerin-sRANKL system.10 An Indian study proposed one way daidzein prevented bone loss was by reversing, "the detrimental immune changes as a result of estrogen deficiency."11 In America, a controlled, parallel-arm, double blind trial involving 145 participants (ages 50 to 80) ingesting a daily soy beverage containing 83 mg of daidzein and genistein over 12 months saw a "modest benefit" in improving the spine's BMD, especially in women.12 A study at the Washington University School of Medicine, St. Louis, involving 43 postmenopausal women revealed soy protein isolate reduced bone turnover with no impact on BMD over nine months.13 Hens consuming 25 ppm of ipriflavone (made from daidzein) not only had greater serum alkaline phosphatase (ALP, an indicator of bone health) and bone GLA-protein levels than controls, their egg production increased, reported scientists from the College of Veterinary Medicine at China's Nanjing Agricultural University.14
Not everyone has rolled out the red carpet for soy. A 2009 randomized, double blind, placebo-controlled clinical trial from the University of Connecticut Health Center evaluated 97 healthy ambulatory women older than age 60.15 After a one-month baseline period, subjects were randomly assigned into an intervention group: soy protein (18 g) plus isoflavone tablets (105 mg isoflavone aglycone equivalents), soy protein plus placebo tablets, control protein plus isoflavone tablets, and control protein plus placebo tablets. The conclusion: soy protein and isoflavones, both individually and together, did not affect BMD. Researchers, however, suggested an alternative: dietary protein.
Dietary protein has long been associated with increased calcium expelled through urine. However, studies have questioned the accuracy of that belief. Increasing dietary protein raises the circulating level of insulin-like growth factor-1, which promotes osteoblast formation and bone growth.16 And an English study claimed protein's effect on bone, "may also depend on intake of [calcium]- and alkali-rich foods [e.g., fruit and vegetables]."17 In addition, that study noted low amounts of protein can reduce insulin-like growth factor production, which has, "a negative effect on calcium and phosphate metabolism, bone formation and muscle cell synthesis."
Magnesium is another category headliner. Though magnesium deficiency is considered a risk factor for osteoporosis, it's unclear how this brisk-selling mineral affects BMD.18 Recent research from Turkey found oral magnesium supplementation in postmenopausal osteoporotic women suppressed bone turnover.19 Thirty consecutive days of oral magnesium supplementation caused significant decreases in serum intact parathyroid hormone levels in the magnesium-supplemented group, which also featured a significant increase in serum osteocalcin levels and a decrease in urinary deoxypyridinoline levels.
Herbs and other agriculture-associated possibilities also abound. Quercetin, a flavonoid found in citrus fruits and vegetables, inhibited bone loss in mice whose ovaries were removed.20 The study, from the University of Tokushima, Japan, saw mice in the quercetin group with "completely" restored bone volume in the distal femoral cancellous bone, though osteoclast surface area and osteoclast number were not reduced. In a Virginia Tech, Blacksburg, study also featuring mice, quercetin protected fetal skeletal delay associated with a diet high in saturated fats.21
A perennial from the grape family, Cissus quadrangularis, has also entered the discussion. A six-month study in 40 perimenopausal women with low BMD showed taking 250 mg of C. quadrangularis extract (as Calzbone®, from Verdure Sciences), three times daily for six months significantly improved the BMD, T score and Z score of treated patients.22 The T score is a measure of the difference between the patient's BMD and the peak bone mass in normal young adults. The Z score measures the difference between the patient's BMD and the mean BMD of age- and gender-matched adults. Calzbone® increased BMD in treated group by more than 17 percent: 0.300 g/cm2 to 0.353 g/cm2, according to the India-based study.
Next: Coleus forskohlii, beta-glucans, red yeast rice, olives and green tea.
Coleus forskohlii, a member of the mint family, contains forskolin, which has been shown to increase bone mass. In a double blind, placebo-controlled study, 30 overweight men received forskolin (as ForsLean®, from Sabinsa) or a placebo for 12 weeks.23 Aside from favorably altering body composition, Forskolin (250 mg 10 percent forskolin twice daily) significantly increased bone mass.
A beta-glucan produced from Aureobasidium pullulans, commonly known as black yeast, has also shown promise. In a randomized, double blind, unpublished study from Chonbuk National University Hospital, Jeonju, South Korea, 60 women received 150 mg/d of the beta-glucan (as Polycan, from Anderson Global Group) for 12 weeks. The subjects' osteocalcin, the key marker for bone formation, increased by 22.7 percent; deoxypyridinoline, the key marker for bone resorption, declined 12.7 percent.
Researchers from Korea's Andong National University observed the methanol extract of red yeast rice extract powder may increase osteogenic effect by stimulating cell proliferation and ALP activity in osteoblastic cells.24 At the University of Hong Kong, bone defects were created in the parietal bones of two New Zealand white rabbits.25 In the test animal, two defects were grafted with collagen matrix mixed with red yeast rice extract. In the control animal, two defects were grafted with just collagen matrix. In the treated animal, red yeast rice extract stimulated new bone formation in bone defects in vivo and increased bone cell formation in vitro.
More compounds helpful for bone health can be found in olives. At Hospital Universitario Reina Sofía in Spain, scientists examined the effects of the polyphenol oleuropein on the processes of osteoblastogenesis and adipogenesis in mesenchymal stem cells from human bone marrow.26 Oleuropein reduced "the expression of peroxisome proliferator-activated receptor gamma (PPARγ), inhibit[ed] adipocyte differentiation, and enhanc[ed] differentiation into osteoblasts." Conclusion: oleuropein could prevent age-related bone loss and osteoporosis. A Japanese study found oleuropein (10 to 100μM) and hydroxytryrosol (50 to 100μM), another polyphenol found in olives, "suppressed the bone loss of trabecular bone" in the femurs of ovariectomized mice.27
Drinking water supplemented with antioxidant-rich green tea displayed a wealth of benefits, according to researchers at Texas Tech University Health Sciences Center, Lubbock.28 Ten middle-aged female rats, with and without their ovaries, were given drinking water containing zero, 0.1 or 0.5 percent green tea polyphenols (GTPs) for 16 weeks. The GTPs mitigated deterioration in both sets of rats by suppressing bone erosion, enhancing bone formation, and modulating endocortical and cancellous bone compartments. The result: a larger net bone volume. University researchers also supplemented GTPs and alfacalcidol in the drinking water of female rats previously administered lipopolysaccharide.29 Results showed "significant interactions in femoral mass and strength, trabecular separation, osteoclast number and tumor necrosis factor-alpha expression in proximal tibia. A combination of both showed to sustain bone microarchitecture and strength," according to the study. Green tea catechins may suppress lipopolysaccharide-induced resorption by inhibiting interlukin-1beta production or by "directly inhibiting" the building of osteoblasts, according to a study from the Nagasaki University Graduate School of Biomedical Sciences, Japan.30
With the help of nutritional ingredients, Americans can take steps to improve bone health throughout their lifetimes.
Still need to bone up on ingredients for bone health? Check out INSIDER's slide show, " Bone Health Beyond Calcium ."
Pete Croatto has written about the natural products industry since 2003. His articles have appeared in Natural Products Marketplace, Life Extension, Natural Foods Merchandiser and others. He is also the Supplements Community Manager of the SupplySide Community (Community.SupplySideShow.com).
References listed on the next page.
1. Guillerminet F et al. "Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice." Osteoporos Int. 2011 Sep 17. [Epub ahead of print]
2. Hooshmand S et al. "Evidence for Bone Reversal Properties of KoACT®, a Novel Dietary Supplement." Presented at American Society for Bone and Mineral Research's 2011 meeting.
3. Greene DA, Naughton GA. "Calcium and vitamin-D supplementation on bone structural properties in peripubertal female identical twins: a randomised controlled trial." Osteoporos Int. 2011 Feb;22(2):489-98. Epub 2010 Jun 11.
4. Tenta R et al. "Calcium and vitamin D supplementation through fortified dairy products counterbalances seasonal variations of bone metabolism indices: the Postmenopausal Health Study." Eur J Nutr. 2011 Aug;50(5):341-9. Epub 2010 Dec 14.
5. Ahmadieh H, Arabi A. "Vitamins and bone health: beyond calcium and vitamin D." Nutr Rev. 2011 Oct;69(10):584-98. doi: 10.1111/j.1753-4887.2011.00372.x.
6. Sahni S et al. "High vitamin C intake is associated with lower 4-year bone loss in elderly men." J Nutr. 2008 Oct;138(10):1931-8.
7. Shuid AN et al. "Vitamin E exhibits bone anabolic actions in normal male rats." J Bone Miner Metab. 2010 Mar;28(2):149-56. Epub 2009 Sep 25.
8. Bulló M, Estruch R, Salas-Salvadó J. "Dietary vitamin K intake is associated with bone quantitative ultrasound measurements but not with bone peripheral biochemical markers in elderly men and women." Bone. 2011 Jun 1;48(6):1313-8. Epub 2011 Apr 5.
9. Fujioka M et al. "Differential effects of isoflavones on bone formation in growing male and female mice." Metabolism. 2007 Aug;56(8):1142-8.
10. Bitto A et al. "Genistein aglycone: a dual mode of action anti-osteoporotic soy isoflavone rebalancing bone turnover towards bone formation." Curr Med Chem. 2010;17(27):3007-18.
11. Tyagi AM et al. "Daidzein prevents the increase in CD4+CD28null T cells and B lymphopoesis in ovariectomized mice: a key mechanism for anti-osteoclastogenic effect." PLoS One. 2011;6(6):e21216. Epub 2011 Jun 22.
12. Newton KM et al. "Soy protein and bone mineral density in older men and women: a randomized trial." Maturitas. 2006 Oct 20;55(3):270-7. Epub 2006 May 26.
13. Evans EM et al. "Effects of soy protein isolate and moderate exercise on bone turnover and bone mineral density in postmenopausal women." Menopause. 2007 May-Jun;14(3 Pt 1):481-8.
14. Yao J, Zhang J, Hou JF. "Effects of ipriflavone on caged layer bone metabolism in vitro and in vivo." Poult Sci. 2007 Mar;86(3):503-7.
15. Kenny AM et al. "Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial." Am J Clin Nutr. 2009 Jul;90(1):234-42. Epub 2009 May 27.
16. Dawson-Hughes B. "Calcium and protein in bone health." Proc Nutr Soc. 2003 May;62(2):505-9.
17. Ginty F. "Dietary protein and bone health." Proc Nutr Soc. 2003 Nov;62(4):867-76.
18. Ishimi Y. "Nutrition and bone health. Magnesium and bone. [Article in Japanese]" Clin Calcium. 2010 May;20(5):762-7.
19. Aydin H et al. "Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women." Biol Trace Elem Res. 2010 Feb;133(2):136-43. Epub 2009 Jun 2.
20. Tsuji M et al. "Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice." J Bone Miner Metab. 2009;27(6):673-81. Epub 2009 Jun 4.
21. Liang C et al. "Gestational high saturated fat diet alters C57BL/6 mouse perinatal skeletal formation." Birth Defects Res B Dev Reprod Toxicol. 2009 Oct;86(5):362-9.
22. Deshmukh VS et al. "Efficacy of Cissus Quadrangularis in Perimenopausal Low Bone Density Women." The Antiseptic. 2011 Oct;108(10):504-06
23. Godard MP, Johnson BA, Richmond SR. "Body composition and hormonal adaptations associated with forskolin consumption in overweight and obese men." Obes Res. 2005 Aug;13(8):1335-43.
24. Cho YE et al. "Red yeast rice stimulates osteoblast proliferation and increases alkaline phosphatase activity in MC3T3-E1 cells." Nutr Res. 2010 Jul;30(7):501-10.
25. Wong RW, Rabie B. "Chinese red yeast rice (Monascus purpureus-fermented rice) promotes bone formation." Chin Med. 2008 Mar 29;3:4.
26. Santiago-Mora R et al. "Oleuropein enhances osteoblastogenesis and inhibits adipogenesis: the effect on differentiation in stem cells derived from bone marrow." Osteoporos Int. 2011 Feb;22(2):675-84. Epub 2010 May 21.
27. Hagiwara K et al. "Olive polyphenol hydroxytyrosol prevents bone loss." Eur J Pharmacol. 2011 Jul 15;662(1-3):78-84. doi: 10.1016/j.ejphar.2011.04.023. Epub 2011 Apr 27.
28. Shen CL et al. "Green tea polyphenols mitigate deterioration of bone microarchitecture in middle-aged female rats." Bone. 2009 Apr;44(4):684-90. Epub 2008 Dec 11.
29. Shen CL et al. "Protective actions of green tea polyphenols and alfacalcidol on bone microstructure in female rats with chronic inflammation." J Nutr Biochem. 2011 Jul;22(7):673-80. Epub 2010 Oct 30.
30. Nakamura H et al. "Green tea catechin inhibits lipopolysaccharide-induced bone resorption in vivo." J Periodontal Res. 2010 Feb;45(1):23-30. Epub 2009 Jul 8.
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