Bone health’s latest ingredient science.
Veterans of the rough-and-tumble of the dietary supplements trade know: This business ain’t beanbag. We’re no strangers to scrutiny, and the prying eyes of regulatory watchdogs are par for our professional course. But when controversy erupted earlier this year over the merits of supplementing with calcium and vitamin D—calcium and vitamin D?!—it felt as if the industry’s very foundations shook.
That’s because calcium and vitamin D are the mom-and-apple-pie of supplementation—our go-to ingredients for keeping bones, along with several other organs and systems, strong and healthy. If we can’t feel confident about them, what can we feel confident about?
But we needn’t worry. Controversy aside, calcium, vitamin D, and a host of other bone-building ingredients demonstrate a proven ability to boost bone health. A quick reminder of how and why they work should reassure us that while controversies come and go, sound science is here to stay.
What could possibly call into question the merits of supplementation with calcium and vitamin D? The first headline-grabber was an epidemiologic study published in May 2012 in Heart Journal (Li et al.). It found a worrying correlation between calcium supplementation and increased risk for myocardial infarction—but several factors about the study suggest that its conclusions might not be as worrisome as the response to them would imply.
First, the study drew those conclusions from a single cohort of a much broader prospective investigation into the relationship between nutrition and cancer—not nutrition and cardiovascular disease. Thus, the researchers didn’t adjust for confounding factors like participants’ age, smoking status, or baseline cholesterol levels that could increase myocardial infarction risk independent of calcium supplementation. Further, users of calcium supplements made up only a small fraction—3.6%—of the cohort’s almost 24,000 participants. With a mere seven self-reported cardiovascular events occurring among subjects supplementing solely with calcium, the association between the mineral and myocardial infarction appears thin.
Thinning it further are questions about a possible mechanism of action. Taylor Wallace, PhD, senior director, scientific and regulatory affairs, Council for Responsible Nutrition (CRN; Washington, DC), says that one “downfall” of epidemiologic studies like this is that “they don’t really pinpoint a biologically plausible mechanism” for how calcium, either dietary or supplemental, could increase cardiovascular risk. “In fact,” he says, “many randomized controlled trials show the exact opposite—that calcium supplements can actually help improve blood lipid levels, decrease blood pressure, and have a positive effect on the validated biomarkers of cardiovascular disease.”
Ultimately, says Cara Welch, PhD, senior vice president, scientific and regulatory affairs, Natural Products Association (NPA; Washington, DC), the study’s conclusion—“or at least the conclusion that was expressed in the media”— is “a stretch, at best. Making a headline and subsequent media frenzy out of this observation is irresponsible.”
Taken to Task
Which brings us to the next media frenzy. Barely a month after the Heart Journal study, the U.S. Preventative Services Task Force (USPSTF) released its draft guidance on calcium and vitamin D supplementation. Relying largely on clinical data from the Women’s Health Initiative (WHI), the USPSTF advised against supplementing with 400 IU or less of vitamin D3 and 1,000 mg or less of calcium carbonate per day for the primary prevention of fractures in noninstitutionalized postmenopausal women, stating that evidence was insufficient to show that taking the nutrients for that purpose was safe.
While the media tended to interpret this as a blanket judgment against vitamin D and calcium supplementation, that conclusion erases considerable nuance from the findings. To wit, the USPSTF acknowledged the need for more research on whether supplementation at levels above 400 IU of vitamin D3 and 1,000 mg of calcium carbonate might prove more effective against fractures—and not only in postmenopausal women but among other demographics, as well. It also suggested studying the effects of supplementation with different forms of the nutrients.
Welch notes that the guidelines are “out of step” with Institute of Medicine (IOM) targets of 600 to 800 IU of vitamin D and 700 to 1,300 mg of calcium per day, depending on age. And those IOM numbers may better reflect biological reality anyway; as Michael McBurney, head of scientific affairs, DSM Nutritional Products (Parsippany, NJ), notes, the IOM “evaluated the relationship between calcium retention with calcium intake and serum 25-hydroxyvitamin D concentrations with bone fracture risk. These are more robust measures of the value of supplementation.”
Keep in mind that the draft recommendations were just that: a draft. As such, NPA’s Welch says, “I wish their conclusions hadn’t generated the amount of media coverage that we saw.” But the controversy appears to have settled somewhat. Noting that her organization’s retailer members haven’t reported drops in vitamin D and calcium supplement sales, “or even much concern expressed by their customers,” Welch trusts that “consumers are confident in the benefits of vitamin D and calcium due to years of safe use and hundreds of studies promoting bone health.”
Their confidence, and ours, makes sense in light of the relationship between nutrition and bone health. Our skeletons exist in a constant cycle of building up and breaking down. As we grow, we add bone mass by extracting raw materials from the diet—or from supplements. After our bones reach their peak mass around age 30, the building-up/breaking-down balance tilts increasingly toward the latter, a process known as resorption. When the body can no longer adequately replace the bone it loses through resorption, osteoporosis results.
According to the International Osteoporosis Foundation (Nyon, Switzerland), the global incidence of osteoporotic fractures is 8.9 million annually, or roughly one every three seconds. Such breaks “are crippling events, shortening lives and robbing sufferers of quality of life through poor healing and ensuing complications,” says Vladimir Badmaev, MD, PhD, head of R&D, NattoPharma (Oslo, Norway). Yet while we associate osteoporosis with aging, “this negative impact of poor bone condition on overall health affects not only boomers and older individuals but also starts affecting Generation Xers in their thirties and mid-forties,” he says.
Calcium to the Core
The trick to reducing osteoporosis risk among young and old lies in maximizing bone mass, and that means feeding bones the right nutrients at the right time. Calcium, the chief mineral in bone, is tops. As CRN’s Wallace says, “We know that if you get adequate amounts of calcium, your bones become stronger—the micro-architecture of the bones becomes more compact and firm.”
But because the ramp-up toward peak bone mass occurs in childhood, Sarah Staley, vice president, business development, FrieslandCampina Domo (Paramus, NJ), stresses that “adequate calcium absorption is a key need for growing children.”
Unfortunately, even with supplementation, more than one-third of children fail to meet calcium recommendations, according to an analysis of National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2006, published online in June 2012 in The Journal of Pediatrics (R Bailey et al.). And because calcium absorption decreases with age, it’s even more imperative that “at-risk and vulnerable groups benefit from foods and dietary components that have the ability to enhance mineral absorption and potentially have a positive impact on long-term bone health,” Staley says.
A “D” for Effort
Enter vitamin D. In its active form—the hormone calcitrol—vitamin D “helps absorb calcium from the intestinal tract and bring it to the bones,” explains A. Karine Dedman, Active Nutrition, DuPont Nutrition & Health (Paris). If the body can’t capture enough calcium from the intestinal tract, it’ll take it from the bones instead, setting the stage for bone loss.
Vitamin D aids bones in other ways, too. Falls lead to fractures and fractures lead to falls, and vitamin D prevents both by helping muscles synthesize proteins for strength and function. Active vitamin D also stimulates the production of osteocalcin, which can “bind calcium to the bones and inhibit calcium deposits in the arteries,” Dedman says.
A Complex Vitamin
Osteocalcin is a vitamin K–dependent protein. It needs vitamin K as a cofactor in the carboxylation reaction that triggers its own activation. “K vitamins were previously only recognized for their role in blood-clotting processes,” Dedman says, “but today we know that the functions of this vitamin group are much more complex.” And much more specific, as not all K vitamins are created equal.
While all share the structural feature of a central quinone ring, vitamin K1, or phylloquinone, has a side chain consisting of four isoprenoid residues, one of which is unsaturated. Vitamin K2, which occurs in several forms collectively known as the menaquinones, can have a variable number of unsaturated isoprenoid residues in its side chain.
With a quinone ring at their heart, all K vitamins operate via a similar principle mechanism. But it’s the length of the side chain and its effect on lipophilicity that determine a particular K vitamin’s bioavailability. In general, Dedman says, the long-chain menaquinones—like vitamin K2 MK-7, with seven residues in its side chain—“are more effective in securing bone health than vitamin K1 or short-chain menaquinones like MK-4.”
Natto, a traditional Japanese food made from fermented soybeans, is “the best-known source of natural vitamin K2,” Dedman says, and MK-7 is its dominant menaquinone. DuPont Danisco took a cue from natto in designing its ActivK brand vitamin K ingredients, emphasizing MK-7 content in their formulations. The version called ActivK N is itself a natural extract of natto, made via controlled fermentation by a non-GMO strain of microorganisms on proteins from non-GMO soybeans.
“Numerous studies have confirmed the link between natto consumption in Japan and significant improvements in vitamin K status and bone health,” Dedman notes. But when intervention trials have tested supplemental doses of MK-7 for periods lasting a year or less, they haven’t produced the health improvements that researchers would expect.
That track record changed, though, with a study (C Vermeer et al.) funded and presented by NattoPharma at this year’s Vitafoods trade show in Europe. The double-blind randomized clinical trial evaluated the results of three years’ daily supplementation with 180 µg of MK-7 in a population of 244 healthy postmenopausal Dutch women aged 55 to 65. The women were randomly assigned to receive either MK-7—in the form of NattoPharma’s MenaQ7, a natural, branded vitamin K2 produced by Bacillus subtilis natto fermentation—or a placebo.
The study demonstrated MK-7’s clinically statistically significant protection against osteoporosis in the vertebrae and femoral neck, and against age-related stiffening of the arteries. But perhaps more notable was the length of time the results took to emerge: no sooner than two to three years into the supplementation regimen.
“This finding explains for the first time why shorter studies—12 months, as cited above—typically failed to show benefits of vitamin K on bone and cardiovascular health,” Badmaev says. Further, the study used a nutritional, not pharmacological, dose—180 µg of vitamin K per day as opposed to as much as 45 mg. And that, Badmaev says, is “a dose that can be obtained from a healthy Western-type diet.” Or from supplements.
More Good News
Other bone health products that withstand scientific scrutiny include galacto-oligosaccharides (GOS), dairy-derived prebiotics fermented in the gut to produce short-chain fatty acids that lower colonic and fecal pH—and, consequently, help solubilize bound calcium and improve its absorption.
Staley’s company, FrieslandCampina Domo, produces a branded GOS called Vivinal GOS. When it undergoes fermentation, she says, it appears to increase secretion of the calcium transporter protein calbindin, further facilitating calcium uptake and absorption. In the roughly 10 studies—a mix of company-conducted/funded studies and peer-reviewed journal studies—that currently support its benefits, “Different dosages showed a significant increase in calcium absorption, as well as magnesium and phosphorous where studied.” Studies involving bone measurements showed an increase in limbic bone mineral content. Staley suggests a daily dose of 5 g “for delivery of health benefits.”
Calzbone Extract is another branded product that its maker, Verdure Sciences (Noblesville, IN), claims has a demonstrated ability to boost bone mineral density and improve bone health. In a 26-week clinical study published in October 2011 in The Antiseptic (V Deshmukh et al.), a 250-mg dose of the botanical extract administered three times daily significantly improved bone mineral density 18% from baseline in the 40 healthy women, aged 45 to 55, who were the study’s subjects. “These findings,” the company wrote in a press release, “suggest strong potential for the use of Calzbone to support bone strength and healthy bone density.”
The product contains what the company calls a “proprietary natural spectrum” of phytohormones, phytosterols, calcium, and vitamin D. Interestingly, it’s derived from a climbing vine of the grape family, Cissus quadrangularis, that practitioners of Ayurvedic medicine have nicknamed—for reasons that should now be apparent—the “bone setter.” After centuries of use in that Indian tradition, it’s still attracting attention and giving hope that, centuries from now, supplements of calcium, vitamin D, and their bone health companions may do the same.