Perplexity is the beginning of knowledge

–Khalil Gibran

n essence, the dietary factors needed to support and maintain healthy bone are the same ones needed to combat all of the degenerative processes of aging. It’s no coincidence, for example, that age–related bone loss directly parallels other age–related phenomena such as joint degeneration, arterial and soft tissue calcification, hormonal imbalance, kidney and liver dysfunction, blood lipid disorders, and blood sugar dysregulation.

But, by looking at bone metabolism in particular, we’ll gain an understanding of exactly how and why all manifestations of aging are related; and we’ll be able to concoct a food a supplement program which will not only protect our bones, but our entire body from the relentless assault of aging.

In the previous articles in this series, we looked at the hormonal contributions to bone loss, and saw that many potent hormonally–active substances in foods and nutritional supplements may be apt to disrupt proper bone building and other aspects of metabolism. We’ll now examine nutrients which are apt to be especially helpful for building strong bones, while supporting the overall health of the body as well.

Beyond Calcium

The role of calcium as a structural component of bone is well–recognized, but the fundamental factor underlying bone loss in aging is often not a calcium deficiency per se, but rather, the age–related decline in proper cellular energy production. That is to say, in aging, even though abundant amounts of calcium may be present (due to supplementation or a carefully selected diet), bone building is often compromised not due to a lack of “building materials,” but due to disorders in the cellular “assembly lines” which produce energy, and ultimately support the structure of all of our cells.

Such disorders of energy production alter calcium–handling by the cells, and are the reason that aging is characterized by the reduced deposition of calcium in bone, with the concomitant increased deposition of calcium in soft tissues such as the arteries, brain and kidneys. Fortunately, physiologically–sound strategies to prevent bone loss should also reduce the pathological calcifications of aging as well.

Correcting a calcium deficiency if one exists is an important first step in the nutritional approach to supporting healthy bones, but in light of rampant calcium supplementation in recent years, caution should be taken to prevent the intake of excess calcium. Rather than indiscriminately consuming calcium supplements, it’s likely that most people should focus their attention on obtaining the many accessory nutrients needed for proper calcium metabolism.

Vitamin D

Perhaps the most well–known of these nutrients is vitamin D. In recent years, it has become well–documented that Vitamin D can, indeed, improve calcium absorption and metabolism:

Study Link – Optimal vitamin D status for the prevention and treatment of osteoporosis.

Quote from the above study:

Vitamin D(3) (cholecalciferol) sufficiency is essential for maximizing bone health. Vitamin D enhances intestinal absorption of calcium and phosphorus…Patients being treated for osteoporosis should be adequately supplemented with calcium and vitamin D to maximize the benefit of treatment.

And the recent media coverage of vitamin D research is an encouraging sign that the integrated nature of nutrition is beginning to be widely recognized. Even many mainstream physicians and health experts now recommend vitamin D in doses well above the recommended daily allowances (RDAs) to prevent age–related bone loss. But in supporting bone health, even calcium and vitamin D may merely be the tip of the nutritional iceberg.

Vitamin K

Vitamin K plays a unique role in supporting proper calcium deposition in bone, while at the same time preventing age–related soft tissue calcification. Biochemically speaking, vitamin K functions as a cofactor for the enzyme which catalyzes the carboxylation of glutamic acid to form gama–carboxyglutamate (Gla). The proteins upon which Vitamin K performs this vital function just so happen to all be involved in proper calcium binding.

Vitamin K increases the activity of the bone–building protein, osteocalcin (while synergistically, the active form of Vitamin D is thought to increase osteocalcin production). Vitamin K also activates matrix Gla Protein (MGP) which is thought to be responsible for preventing calcification of the soft tissues such as the arteries and cartilage.

Study Link – Role of vitamin K and Gla proteins in the pathophysiology of osteoporosis and vascular calcification.

Quote from the above study:

Osteocalcin metabolism has been implicated in the pathogenesis of osteoporosis through an unknown mechanism that may be linked to suboptimal vitamin K status resulting in its undercarboxylation and presumed dysfunction. Recent studies that have investigated this hypothesis are discussed, as are recent promising clinical studies of vitamin K supplementation in osteoporosis. A recently delineated function of matrix Gla protein is as a powerful inhibitor of calcification of arteries and cartilage.

As evidence of their synergy, the combination of Vitamin D and Vitamin K has been shown to help maintain the healthy elasticity of the arterial wall in post–menopausal women:

Study Link – Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow–up study.

Quote from the above study:

It is concluded that a supplement containing vitamins K1 and D has a beneficial effect on the elastic properties of the arterial vessel wall.

Yet, despite Vitamin K’s remarkable ability to build bone and prevent arterial calcification (aka the “hardening of the arteries” characteristic of heart disease), the vitamin is probably most well–known for its role in blood clotting. Because blood which clots excessively is itself thought to be a risk factor for heart disease, the anti–coagulant drug, warfarin, is often used in cardiac patients. It’s for this reason that patients taking warfarin are often advised to avoid foods containing Vitamin K. But warfarin, which acts specifically by antagonizing the function of Vitamin K, has often been shown to increase arterial calcification..

Study Link – Warfarin exposure and calcification of the arterial system in the rat.

Quote from the above study:

Sprague–Dawley rats were treated from birth for 5–12 weeks with daily doses of warfarin and concurrent vitamin K1. This treatment causes an extrahepatic vitamin K deficiency without affecting the vitamin K–dependent blood clotting factors. At the end of treatment the rats were killed and the vascular system was examined for evidence of calcification. All treated animals showed extensive arterial calcification…It is likely that humans on long–term warfarin treatment have extrahepatic vitamin K deficiency and hence they are potentially at increased risk of developing arterial calcification.

Traditionally, researchers assumed that an adequate level of vitamin K was simply one which allowed for proper blood clotting. And since most of the vitamin K–dependent blood–clotting proteins are synthesized by the liver, it makes sense that the liver tends to accumulate Vitamin K at a higher rate than the rest of the body. But in the above study, researchers discovered that extrahepatic (outside of the liver) vitamin K deficiency (such as that caused by warfarin) can lead to arterial calcification, even when hepatic vitamin K levels remain adequate to support blood clotting.

Like the prevention of arterial calcification, bone–building is largely dependent on adequate vitamin K levels throughout the body; and in some (but not all) studies, warfarin, by causing a relative extrahepatic vitamin K deficiency, has been shown to increase the risk of osteoporosis – at least in men:

Study Link – Risk of Osteoporotic Fracture in Elderly Patients Taking Warfarin.

Quote from the above study:

Long–term use of warfarin was associated with osteoporotic fractures, at least in men with atrial fibrillation.

Noting the previously unrecognized roles of Vitamin K in supporting bone calcification while preventing soft tissue calcification, some researchers have asserted that the recommended daily allowance of the nutrient should be increased to higher levels than those needed for proper blood clotting:

Study Link – Role of vitamin K and vitamin K–dependent proteins in vascular calcification.

Quote from the above study:

The hypothesis is put forward that undercarboxylation of MGP is a risk factor for vascular calcification and that the present RDA values are too low to ensure full carboxylation of MGP.

Vitamin K occurs in two major forms – K1 (K1 comprises both phylloquinone – the natural version of K1 found mostly in green leafy vegetables such as spinach, and phytonadione – the synthetic version of K1 often found in supplements); and K2 (menaquinone – which is produced by intestinal bacteria, and can be found in some fermented foods, such as natto).

For dietary vitamin K, green leafy vegetables are among the best sources. Many vegetable oils also contain vitamin K, but their use should be avoided as much as possible. Vegetable oils contain other substances which are likely to decimate bone and overall health.

And although the “good” intestinal bacteria are known to produce Vitamin K2, there exists some question as to how well–absorbed and utilized this bacterial–derived vitamin K is in humans. Recent research, however, has indicated that there may be unique benefits to supplementing with some types of vitamin K2:

Study Link – Vitamin K2 improves bone strength in postmenopausal women.

Quote from the above study:

High vitamin K intake is associated with improved bone health and prevention of osteoporotic fractures. At nutritional doses, both vitamins K 1 and K 2 may contribute to optimizing bone mineral density; intervention studies suggest a synergistic effect with vitamin D and calcium. At higher intakes, vitamin K was demonstrated to also increase bone strength by improved bone geometry, but this effect was restricted to K 2.

Magnesium

According to data compiled by the United States Department of Agriculture, the diets of 68% of Americans fail to provide the recommended daily intake of magnesium each day. And where magnesium is involved in at least 325 known biochemical processes in the body, it’s easy to imagine how such a chronic magnesium deficiency can serve to decimate our health.

In previous Integrated Supplements Newsletters we’ve seen how magnesium deficiency alone can dramatically increase almost every known marker of inflammation and cellular destruction. Along these lines, and as relates to bone health, the research makes it very clear that magnesium deficiency causes an increase in the function of bone–destroying osteoclasts while at the same time inhibiting the proper function of the bone–building osteoblasts – the end result being massive bone loss:

Study Link – Magnesium deficiency–induced osteoporosis in the rat: uncoupling of bone formation and bone resorption.

Study Link – Magnesium deficiency induces bone loss in the rat.

Study Link – Reduction of dietary magnesium by only 50% in the rat disrupts bone and mineral metabolism.

Study Link – Prolonged magnesium deficiency causes osteoporosis in the rat.

In the United States, and many other industrialized countries, where calcium–rich foods are relatively common, it may be the case that magnesium deficiency plays an even greater role in bone loss than calcium deficiency. In some studies, magnesium supplementation alone has led to remarkable increases in bone density in post–menopausal women. It’s worth noting that many interventions are deemed successful if they merely inhibit or slow the rate of bone loss in this population. The following study found that 71% of patients treated with magnesium supplements responded with a 1% to 8% increase in bone density, whereas in the untreated control group, bone density decreased significantly:

Study Link – Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis.

Quote from the above study:

Twenty–two patients (71 per cent) responded by a 1–8 per cent rise of bone density. The mean bone density of all treated patients increased significantly after 1 year (P < 0.02) and remained unchanged after 2 years (P > 0.05). The mean bone density of the responders increased significantly both after one year (P < 0.001) and after 2 years (P < 0.02), while in untreated controls, the mean bone density decreased significantly (P < 0.001).

In the above study, success was achieved even though magnesium hydroxide was used – a magnesium source with relatively poor absorption, which is commonly used as a laxative. It’s likely that magnesium sources with higher bioavailability would yield even better results.

Along these lines, many calcium– and magnesium–containing supplements contain magnesium in the form of magnesium oxide – also a relatively poor choice all things considered.

Magnesium oxide is commonly used in nutritional supplements because, chemically, it contains a relatively high percentage of elemental magnesium. This means that companies using magnesium oxide are able to include relatively high amounts of magnesium in their products on a per–pill or per–dose basis. But, as with all nutrients, it’s not just how much magnesium we swallow that matters – it’s how much we actually absorb and utilize. Magnesium oxide happens to be notorious for its poor absorption, which is why it, too, is commonly used as an osmotic laxative. Unabsorbed magnesium oxide in the gastrointestinal tract draws water into the intestines which can cause this laxative effect, but in order for magnesium to exert its full range of biological benefits, it, logically, must first be absorbed into the bloodstream.

Also relating to magnesium bioavailability, it’s known that calcium can block the absorption and retention of magnesium. So ironically, calcium and magnesium combination supplements could even make magnesium deficiency worse, as most of these formulas contain twice as much calcium as magnesium – and the magnesium they do contain is usually poorly absorbed.

Study Link – Magnesium

Quote from the above study:

In subjects on low Mg intake calcium supplementation seems to reduce dietary Mg retention.

And some calcium and magnesium combination formulas (especially those containing calcium carbonate along with magnesium oxide) may be somewhat prone to cause health problems. The combination of high–dose calcium (above 2 grams per day from all sources including supplements) along with alkali (high pH) substances (such as magnesium oxide) is known to sometimes cause the phenomenon known as the milk–alkali syndrome. The milk alkali syndrome, in which very high amounts of calcium are absorbed and retained, has increased in recent years, due, in part, to widespread calcium supplementation, and is characterized by the pathological calcification of the kidneys, lungs, vasculature, and gastric mucosa. Elderly people and/or those with compromised kidney (renal) function are particularly susceptible:

Study Link – Milk Alkali Syndrome and the Dynamics of Calcium Homeostasis.

Quote from the above study:

More recently, the milk alkali syndrome has been reported in older women who receive calcium supplements for osteoporosis. Aging has several effects that affect calcium homeostasis. These include a decrease in the efficiency of intestinal calcium absorption, a reduced capacity to deposit calcium in bone, and a decrease in renal function. In general, the overall effect of aging is a reduced capacity to handle a calcium load that sensitizes the elderly to the development of hypercalcemia.

Diagnosis of the milk–alkali syndrome is still relatively rare, but the very real possibility for harm is reason enough to choose our supplements carefully. Thought should always be given to the dosages taken, the forms of the nutrients being used, and to possible nutrient interactions.

With calcium–rich foods being relatively common in our food supply, and with magnesium–rich foods being relatively rare, it’s likely that a stand–alone magnesium supplement will be of immense value to most people – especially those looking to support bone health.

As relates to magnesium supplementation, significant amounts of magnesium oxide should be avoided in favor of magnesium chelated (chemically attached) to certain amino acids (such as glycine, i.e., magnesium glycinate), or organic acids (such as malic acid, i.e. magnesium malate). Not only will these compounds offer efficient absorption, but glycine and malic acid are among the safest ligands for mineral binding. They are likely to offer benefits and safety profiles above and beyond other ligands like citric acid (magnesium citrate) or aspartic acid (magnesium aspartate).

Whey Protein

As was previously noted, many foods widely available to us are significant sources of calcium – the most obvious, of course, being dairy foods. But some dairy foods – depending largely upon how they’re processed – may offer unique benefits for bone health above and beyond just the calcium they contain. One such “functional” dairy food is whey protein. Whey protein will contain calcium, but whey protein which has been filtered in such a way as to maintain the integrity of its protein structures is likely to impart several additional benefits to bone health.

Research has shown whey protein to stimulate the activity of the bone–building osteoblasts:

Study Link – Whey Protein Stimulates the Proliferation and Differentiation of Osteoblastic MC3T3–E1 Cells.

Quote from the above study:

This protein caused dose–dependent increases in [3H]thymidine incorporation and DNA content in the cells. It also increased the total protein and hydroxyproline contents in the cells…these active components can possibly permeate or be absorbed by the intestines. We propose the possibility that the active component in the whey protein plays an important role in bone formation by activating osteoblasts.

The above study indicates that certain whey proteins, which are able to be absorbed intact, are likely to be responsible for the bone–building effects of whey – further evidence that the nutritional quality of whey protein goes far beyond it’s amino acid profile, and further reason to consume whey proteins with the highest level of undenatured (unaltered) proteins possible.

For example, it’s likely that the minor whey protein fraction, lactoferrin, is largely responsible for the unique bone–building effects of whey:

Study Link – Lactoferrin Is a Potent Regulator of Bone Cell Activity and Increases Bone Formation in Vivo.

Quote from the above study:

Lactoferrin produced large, dose–related increases in thymidine incorporation in primary or cell line cultures of human or rat osteoblast–like cells, at physiological concentrations (1–100 µg/ml). Maximal stimulation was 5–fold above control. Lactoferrin also increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50–70%... Thus, lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis. Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth.

As we saw in our series of newsletters on iron and aging, limiting iron–induced oxidative damage should be a fundamental goal of any anti–aging nutritional strategy. As an iron–binding protein, lactoferrin has repeatedly been shown to protect cells from the harmful effects of free iron, and it’s likely to be this mechanism which supports bone building as well.

Study Link – Iron loading: a risk factor for osteoporosis.

Quote from the above study:

Iron suppresses bone remodeling apparently by decreasing osteoblast formation and new bone synthesis. Low molecular mass iron chelators as well as a natural protein iron chelator, lactoferrin, may be useful in prevention of osteoporosis.

So, it’s clear that a properly–produced whey protein can play a beneficial role in any bone–building diet. And it’s worth noting that – contrary to popular opinion – increased overall protein intake (including meat) is likely to be of benefit as well.

It’s widely believed (and widely written) that a high protein intake can exacerbate bone loss – the thinking being that calcium is “wasted” to buffer the acidic load of the protein. But the relevant research doesn’t seem to support the idea that protein has a negative influence on bone building. On the contrary, some studies show that protein (and even meat proteins in particular) may offer a distinct benefit to bone health:

Study Link – Effect of Dietary Protein Supplements on Calcium Excretion in Healthy Older Men and Women.

Quote from the above study:

In contrast to the widely held belief that increased protein intake results in calcium wasting, meat supplements, when exchanged isocalorically for carbohydrates, may have a favorable impact on the skeleton in healthy older men and women.

In the following study, bone mineral density (BMD) of the hip was found to be lower in vegetarians and lactovegetarians and higher in omnivores.

Study Link – Bone mineral density in Chinese elderly female vegetarians, vegans, lacto–vegetarians and omnivores.

Quote from the above study:

There is a relationship between diet and BMD. The BMD at the hip was lower in vegetarians than omnivores, but no difference was observed between 'vegans' and 'lactovegetarians'.

Such studies logically raise the question: Are there nutritional substances unique to meats which may specifically offer benefits towards bone building? There may, in fact, be several such substances – one candidate being the nutritional energy molecule, creatine.

Creatine

Researchers have known for some time that weight–bearing and resistance exercise helps to support bone health. So logically, when creatine supplementation was found to support bone building, many people simply assumed that this effect was due to the nutrient’s well–known ability to support muscular strength:

Study Link – Creatine monohydrate and resistance training increase bone mineral content and density in older men.

Quote from the above study:

…creatine supplementation may provide an additional benefit for increasing regional bone mineral content. The increase in bone mineral content may be due to an enhanced muscle mass with creatine, with potentially greater tension on bone at sites of muscle attachment.

But creatine is likely to do far more for bone health than just energizing the muscles. Subsequent research from cell–culture studies has shown that creatine may be able to directly stimulate metabolic activity in the bone–building osteoblasts themselves:

Study Link – Stimulatory effects of creatine on metabolic activity, differentiation and mineralization of primary osteoblast–like cells in monolayer and micromass cell cultures.

Quote from the above study:

…chemically pure Cr added to low serum cell culture medium has a stimulatory effect on metabolic activity, differentiation and mineralization of osteoblast–like cells indicating that Cr supplementation could also be used as a potential clinical intervention to stimulate cell growth, differentiation and mineralization during bone repair in vivo.

Later studies also showed that creatine, when fed to growing rats, led to an increase in bone mineral density:

Study Link – Creatine monohydrate increases bone mineral density in young Sprague–Dawley rats.

Quote from the above study:

Together, these data suggest that creatine monohydrate potentially has a beneficial influence on bone function and structure; further investigation is warranted into its effect on bone functional properties and its effects in disorders associated with bone loss.

The effectiveness of creatine in bone building is a clear illustration of the fact that the maintenance of our bodily structure is dependent on our cells’ ability to produce energy. Most people fail to recognize that bone isn’t the static entity it’s often assumed to be. Because the breaking down and building up of bone is constantly occurring throughout our lives, bone, and the cells that build bone, are, in fact, quite metabolically active. Maintaining and stimulating the energy–producing machinery in these cells, as creatine does, is likely to keep the entire process functioning efficiently.

Mineral Water & Carbonated Water

In addition to macrominerals like calcium, magnesium, and potassium; the body also requires a host of trace minerals to carry out all metabolic functioning. As relates to bone, research has found that the addition of trace minerals like zinc, manganese, and copper to calcium supplementation offers benefit beyond calcium intake alone:

Study Link – Spinal Bone Loss in Postmenopausal Women Supplemented with Calcium and Trace Minerals.

Quote from the above study:

The effects of calcium supplementation (as calcium citrate malate, 1000 mg elemental Ca/d) with and without the addition of zinc (15.0 mg/d), manganese (5.0 mg/d) and copper (2.5 mg/d) on spinal bone loss (L2–L4 vertebrae) was evaluated in healthy older postmenopausal women (n = 59, mean age 66 y) in a 2–y, double–blind, placebo–controlled trial…The only significant group difference occurred between the placebo group and the group receiving calcium plus trace minerals (P = 0.0099). These data suggest that bone loss in calcium–supplemented, older postmenopausal women can be further arrested by concomitant increases in trace mineral intake.

And numerous studies have shown that mineral waters, which constitute rich sources of both macro– and trace minerals, may be of unique benefit to bone health as well:

Study Link – Consumption of a high calcium mineral water lowers biochemical indices of bone remodeling in postmenopausal women with low calcium intake.

Study Link – Mineral water as a source of dietary calcium: acute effects on parathyroid function and bone resorption in young men.

Study Link – Effect of Calcium Supplementation as a High–Calcium Mineral Water on Bone Loss in Early Postmenopausal Women.

Quote from the above study:

This study provides further evidence to support the use of a high calcium mineral water as an effective prophylaxis against postmenopausal bone loss.

But calcium and other minerals may not be the sole reason for mineral water’s bone–supporting benefits. An often overlooked factor may be the presence of dissolved carbon dioxide which is responsible for the effervescence of these waters.

In the January 2009 edition of the Integrated Supplements Newsletter, we touched upon the fact that the degenerative disorders of aging are all characterized by the development of a “hyperventilated” metabolism. Hyperventilation can be thought of as suffocation despite the presence of oxygen; and although most of us associate hyperventilation with the idea of gasping for breath in the midst of panic or stress, a parallel phenomenon exists on a cellular level with a shift towards glycolytic (anaerobic, sugar–burning) metabolism. In healthy cells, the main goal of glycolysis is simply to “prep” sugar to be burned aerobically (in the presence of oxygen) in the mitochondria (i.e., cellular respiration). But stressed, damaged, and sick cells often derive much of their energy solely from glycolysis. Cancer cells, for example, are notorious for their reliance on glycolysis as a means of energy production.

Healthy cells produce carbon dioxide as a result of cellular respiration, and carbon dioxide allows hemoglobin to release its bound oxygen to the cells. It seems ironic at first – but even though carbon dioxide is a product of respiration, it is also a factor responsible for stimulating respiration as well. When carbon dioxide isn’t produced by the cells properly (i.e., when cellular respiration is hindered, as in aging, stress, or disease), oxygenation of the cells, too, is hindered.

So, one wonders, is it possible to deliver exogenous carbon dioxide to the body in order to improve tissue oxygenation and cellular respiration?

Some biologists may scoff at the idea, but research indicates it may not be all that far–fetched after all.

In hot weather (which is called heat stress), chickens pant to cool themselves – and it’s easy to interpret this sort of short, labored breathing as a type of hyperventilation. Poultry farmers know full–well that heat stress is associated with significantly reduced bone density in these animals, and have often investigated low–cost ways to rectify the problem.

As it turns out, some studies have found that drinking carbonated water (i.e., water without appreciable mineral content, but with carbon dioxide dissolved in it, like seltzer water or soda water) is able to significantly increase the bone strength of egg–laying hens subjected to heat stress:

Study Link – Research note: effect of carbonated drinking water on production performance and bone characteristics of laying hens exposed to high environmental temperatures.

Quote from the above study:

These results suggest that carbonated drinking water may enhance bone integrity by increasing tibia bone breaking strength of older laying hens exposed to a short–term heat stress period.

Other studies have found similar effects in other bird species:

Study Link – Influence of carbonated drinking water on tibia strength of domestic cockerels reared in hot environments.

If water with only carbon dioxide dissolved in it serves so improve cellular respiration and bone health as the above studies indicate, it’s logical that naturally carbonated mineral waters may be a much more powerful tool than is commonly recognized for those looking to support bone health.

Across all effective interventions for maintaining the integrity of bone, one common thread emerges – supporting youthful energy production. There are, of course, several means to this end: e.g., maintaining proper levels of youth–associated hormones, lessening the burden on the bodies detoxifying machinery by avoiding food–based toxins and endocrine disruptors, and supplying the nutrients needed to allow our cells to create energy and adapt positively to various stimuli. Such an integrated approach, using inexpensive and easily available substances, has the potential support not only bone building, but overall health for a lifetime.