Taking a broader view on bone health
Even in the broad view, misconceptions about bones abound. “Bones are often thought of as hard and lifeless, but bones are actually living, growing tissue,” says Kathy Lund, vice president of business development and marketing at AIDP Inc. (City of Industry, CA).
Roughly half of bone mass is made up of inorganic minerals, mainly calcium-phosphate crystals that give bone its density, while the other half comprises mostly collagen, providing calcium with a sturdy yet flexible structure for attachment. Lund likens the arrangement to that of a skyscraper: “Collagen is the steel frame, and calcium is the cement.”
As living, growing tissue, these skeletal skyscrapers are in continuous remodeling mode, with cells called osteoblasts directing the production of new bone through synthesis of collagen matrix and bone mineralization, and other cells, called osteoclasts, resorbing old bone-that is, breaking it down.
Though this breakdown may sound harmful to bone health, it’s a fundamental component. “If micro-damaged bone is not resorbed and effectively removed from the bone matrix, bones may continue to increase in density due to the bone-building process, but they may lose their pliability and strength because of the presence of the old, damaged, or weakened bone,” explains Nena Dockery, technical support for ESM, Stratum Nutrition (St. Charles, MO). The upshot: “The risk of fractures increases.”
Ultimately, healthy bones are those in which resorption more or less balances formation. But that equilibrium can shift in response to diet, illness, smoking status, and activity level, among other factors. “It’s well known that estrogen and other hormones, such as parathyroid hormone, play a significant role in bone health,” notes Lew Hendricks, technical services manager at Innophos Inc. (Cranbury, NJ). “Not surprisingly, we are learning to see bone health from a holistic health perspective.”
Perhaps the strongest shaper of bone health-certainly the most inevitable-is age. During childhood and adolescence, our bones grow vigorously, attaining peak mass between ages 18 and 25. Thereafter, says Lund, “The balance between bone formation and bone loss starts to change by slowly losing more bone than is formed.” This process accelerates in men and women during midlife and really takes off in women following menopause, when estrogen levels drop sharply. “In fact,” Lund says, “in the five to seven years after menopause, women can lose up to 20% or more of their bone.”
Sometimes this results in osteoporosis, a disease in which reduced mass and structural deterioration weaken bones so much that they can break from even minor falls. And osteoporosis is a major public health threat. The World Health Organization places the number of people with osteoporosis at 200 million globally. Their lifetime risk of fracture is nearly one in two for women and one in three for men. And, even if diet, in theory, were sufficient to turn those numbers around, the typical American diet in practice does not. Which makes the same strong case for supplementation that we’ve been making all along. At an estimated cost of $13.8 billion annually, the disease burdens not just its sufferers, but our entire healthcare system.
Osteoporosis is not solely a concern of the elderly. “The idea that women don’t have to worry about osteoporosis until later is grossly misunderstood and wrong,” says Jason Kwon, technical support, Vesta Pharmaceuticals Inc. (Indianapolis). “What recent research has shown is that women who have healthy and higher bone mineral density at a younger age-say, 19 to 23-tend to be less susceptible to fractures and osteoporosis at later ages.” Evidence also suggests that what best develops this bone mineral density is regular weight-bearing exercise and sufficient intake of bone-building nutrients.
Of course, the highest-profile bone-building nutrient is calcium. But calcium is hardly a solo act in fostering skeletal wellness. Calcium relies on an extensive supporting cast. As Dockery says, “Though many still associate bone health with calcium supplementation alone, most scientists have known for decades that other nutrients are crucial to the functioning of calcium in bone health.”
Take vitamin D. This steroid hormone aids in the mineralization of the bone matrix “partially through stimulating intestinal absorption of calcium,” Dockery says. It also participates in healthy bone resorption and helps maintain adequate blood serum calcium and phosphorus levels, she adds.
Vitamin D in its cholecalciferol (or vitamin D3 ) form, is just one component of a patented bone-health supplement from LycoRed (Beer Sheva, Israel). The product, Lyc-O-Fem, combines vitamin D3 with the phytoestrogen genistein and natural tomato lycopene.
Genistein in its aglycone form “appears to be the most effective isoflavone in preserving bone health,” says Tal Offer, PhD, product development manager at LycoRed. The company uses a natural genistein extracted from Sophora japonica-the Japanese Pagoda Tree-standardized to 98% and delivered in a slow-release formulation. “This technology allows better and more convenient compliance due to the ability to maintain a steady-state level of the phytohormone in the body for a longer period of time,” says Offer.
As for the lycopene, not only has it been shown to have a beneficial effect on bone modulation during osteoporosis, but Offer says the carotenoid appears to ameliorate the adverse effects of some forms of hormone replacement therapy. To wit, estrogen-based treatments activate estrogen receptor alpha (ER-α), which “is associated with increased risk of breast cancer and uterine stimulation,” says Offer. “The combination of genistein, an ER-β selective compound, with natural tomato lycopene, which has been found to inhibit estrogen activity in breast cells but not in bone cells, offers an integrative and safe approach.”
Vladimir Badmaev, MD, PhD, head of R&D at NattoPharma ASA (Oslo, Norway), notes that preclinical and human studies credit long-chain polyunsaturated fatty acids with enhancing calcium absorption, reducing urinary calcium excretion, and increasing bone calcium content. In particular, says Badmaev, supplementation with omega-3 DHA appears to correlate significantly with bone density and bone calcium content in studies on experimental animals. Further, he says that DHA supplementation increases absorption of calcium and accrual of calcium in bone significantly more than omega-3 EPA.
Considering collagen’s intimacy with calcium in the skeletal matrix, its supplementation might be a boon to bone health, too. Indeed, research finds that a patented compound of hydrolyzed collagen peptides and calcium “supports increased bone mineral density and flexibility,” says Lund. The compound, called KoACT, delivers collagen and calcium in a form that is said to mimic bone’s natural biological structure. “The result is a synergistic effect of both calcium and collagen in bone, creating superior bone strength,” says Lund.
A human clinical trial on KoACT randomly assigned 20 postmenopausal women to daily supplementation with either 500 mg of elemental calcium (calcium carbonate) or 5 g of KoACT (also with 500 mg of elemental calcium) for three months. Analysis of total-body bone mineral density showed a respective decrease and increase from baseline in the control and KoACT groups, respectively, between which the difference was highly significant. The study will continue to verify the observations through a six-month regime. Lund says the research is pending publication, and specific data may soon be available.
Calcium carbonate-the calcium form used in the aforementioned study-is the most common form of calcium found in nature, and it contains the highest levels of elemental calcium: 35% to 40%, ESM’s Dockery says. But, in the absence of adequate gastric acid, our bodies often inefficiently absorb calcium carbonate. Moreover, calcium carbonate mined from rock or seashell may carry a substantial load of heavy metals, says Dockery.
Eggshell calcium, by contrast, is an all-natural, food-derived form with heavy metal levels well below even California’s strict Proposition 65 mandates, she says. In addition to delivering about 35% elemental calcium, eggshell calcium benefits from specific “transport proteins” that Dockery claims make it “as absorbable as calcium citrate and other highly absorbable forms that contain less elemental calcium.”
But calcium isn’t the only mineral in town. It’s calcium’s partnership with phosphorus, potassium, zinc, manganese, copper, and other minerals that “has proven critical for improving bone health,” says Max Motyka, director of the human products division at Albion Laboratories Inc. (Clearfield, UT).
Magnesium, in particular, pays bone-health dividends by suppressing parathyroid hormone release and thus decreasing osteoclast activity. “This has the net effect of drawing calcium into the bone structure,” says Motyka. “Without magnesium, calcium may not be fully utilized.”
But, for any bone-building mineral to be fully utilized, we must consume it in a bioavailable form. Motyka notes, for example, that individuals vary widely in their ability to absorb different forms of iron. Robab Emami, technical services manager at AMT Labs and Kelatron Corp. (Ogden, UT), divisions of Innophos Inc., adds that in the acidic environment of the stomach, minerals dissociate into charged ions that are attracted to other charged stomach contents-say, fiber and fat. “Therefore, only a small portion of the mineral content will be absorbed,” she says.
Most minerals naturally occur in an inorganic state and require conversion to a stable organic form for optimal absorption. This conversion process is called chelation, says Emami, “where a metal is bonded to an organic ligand, such as an amino acid, to protect the mineral from ionization and optimize its absorption in the body.” Chelation minimizes mineral dissociation in the stomach, which Emami says not only increases absorption but reduces stomach irritation, too.
To be successful, mineral chelates must make it through the stomach intact, so they can pass into the small intestine-the duodenum and jejunum sections-where their chances of absorption are much greater, says Motyka. To produce its specialty Calcium Bisglycinate Chelate, his company uses a patented technology to bond chelated minerals to amino acid ligands, “creating a stable molecule with a neutral charge,” he says. “This molecule passes through the stomach intact and is available for absorption. This is particularly important for bone-health nutrients because the body recognizes the amino acid components as food and absorbs them a little more easily.”
And, while increased mineral uptake may not top the list of prebiotic fiber’s most ballyhooed benefits, Patrick Luchsinger, marketing manager of nutrition at Ingredion (Westchester, IL), points out that his company’s patented prebiotic short-chain fructooligosaccharide, NutraFlora, improves bone strength by improving absorption of minerals like calcium. But how?
As beneficial gastrointestinal bacteria ferment the fiber, they produce short-chain fatty acids that “nourish the gut tissues through which minerals are absorbed,” Luchsinger says, “while at the same time lowering the pH to an optimal level for ionizing and solubilizing minerals.” The most recent study on the fiber’s relationship to bone health has been submitted for review and publication, and scientific studies show that about 3.2 g of NutraFlora per day may significantly and immediately improve calcium and magnesium absorption in human subjects.
The role of minerals in building healthy bone is undisputed. But research raises questions about whether calcium supplementation may do more harm than good-for the heart, that is.
The results of an epidemiological study published in 2013 in the Journal of the American Medical Association (Xiao et al.) indicate that daily intake of 1000 mg of supplemental calcium correlated with significant increases in death from cardiovascular disease (CVD), particularly in men. And, notes NattoPharma’s Badmaev, further studies reveal similar risks in women. “Use of calcium supplements with or without vitamin D was associated with a significant 24% increase in risk of coronary heart disease in a cohort of 10,555 Finnish women,” he says (Pentti K.).
Granted, numerous studies have yielded no evidence of such a link, and calcium’s defenders point out that the calcium-rich DASH (Dietary Approaches to Stop Hypertension) eating plan correlates with positive outcomes for hypertension and cardiovascular health. Nevertheless, the calcium-CVD story is grabbing headlines and crying out for some sort of explanation.
The answer may come in the form of vitamin K2. Badmaev says the nutrient has an increasingly recognized role as a “calcium chaperone”; that is to say, by carboxylating osteocalcin, a protein produced in bone-building osteoblast cells, the fat-soluble vitamin activates the protein, enabling it to shunt calcium out of circulation and into the bone, where it strengthens the collagen-mineral matrix.
Vitamin K2 also carboxylates and activates matrix GLA-protein (MGP), which promotes elasticity and prevents calcification of blood vessels. “This dual function of vitamin K2 is sometimes referred to as the vitamin K paradox,” Badmaev says. “Vitamin K2 helps build calcium deposits in the bone via carboxylated osteocalcin, yet has the opposite effect on the circulatory system by activating MGP, which prevents calcium deposits in the arteries, and is one of the most potent arterial calcification inhibitors known.”
But not all forms of vitamin K2, known as menaquinones, are equally effective. Though vitamin K forms share the structural similarity of a central quinone ring, the length of their isoprenoid side chains distinguishes each form-and determines its biological activity. The side chain of menaquinone-7, or MK-7, has seven isoprenoid units, and evidence suggests that MK-7, more than shorter-chain forms MK-4 and MK-5, optimally promotes bone and cardiovascular health.
A double-blind randomized clinical trial published this year in Osteoporosis International (Knapen et al.) evaluated a three-year daily supplementation regime of 180 mcg of MK-7-in the form of NattoPharma’s MenaQ7-among 244 healthy post-menopausal women ages 55 to 65. The results showed that this sub-pharmacological, nutritional dose provided statistically significant cardiovascular protection and improved bone and metabolic health. The trial also showed that a nutritional MK-7 dose provides substantial benefits in preventing age-related stiffening of the human arteries.
But while the dose was indeed “nutritional,” getting even that much MK-7 from diet alone is challenging. The flagship food source of vitamin K2 in its MK-7 form is natto, a traditional Japanese preparation of fermented soybeans. Given that natto is at best an “acquired taste” for American palates, consumers here may choose to look elsewhere for their MK-7.
Again, supplementation could save the day. “It has become increasingly obvious that the current status of nutritional supplementation, especially with vitamin K2 subtypes, is insufficient,” Badmaev says. “Additional supplementation with vitamin K2 may help prevent osteoporosis and cardiovascular disease in both men and women.”
In fact, Badmaev sees vitamin K2, calcium, and other bone-building supplementation as united in a “new paradigm” that “makes bone health an integral part of general well being.” This paradigm, he predicts, will “advocate the use of multiple synergistic nutrients” that not only interact in complex ways with each other, but go beyond bones to effect changes in everything from the heart to the inflammatory response. So stick around. Things are bound to get interesting.