Original Article

Assessment Of A Nutrient-Based Approach On Bone Health

J Blum

Keywords

bone health, nutrients, osteopenia, osteoporosis, supplementation

Citation

J Blum. Assessment Of A Nutrient-Based Approach On Bone Health. The Internet Journal of Alternative Medicine. 2006 Volume 4 Number 2.

Abstract


Background: Complementary and alternative medicine use in adults with, or at risk for, osteopenia is common. Although most of the herbs and supplements appear to be fairly safe, there is insufficient evidence that demonstrates their beneficial effects.

Aim of the Study: This study was done to determine whether the current nutrients improve indicators of calcium metabolism and bone status.

Materials and Methods: This human clinical trial was randomized, double-blind, placebo-controlled, and prospective in design. Of a population of 72 individuals who were screened over the telephone, 47 post-menopausal females age 50-75 were included in the study. The enrolled subjects were randomly assigned to receive the active product or placebo, one capsule four times per day for six weeks. The major outcome variables were 24-hour urinary calcium per gram of creatinine, serum Bone Specific Alkaline Phosphatase (BSAP), C-Terminal Telopeptide (CTX), and Osteocalcin (OST).

Results: At the conclusion of the study, subjects who received the active product showed reduction in the 24-hour urinary calcium loss and serum CTX levels. They revealed an increase in BSAP and no change was noted for OST.

Conclusions: Nutrient-based supplementation is able to improve measures of calcium metabolism and bone health in post-menopausal females. Studies of longer duration using endpoints including fracture incidence and bone densitometry should be conducted in the future.

 

Introduction

Loss of skeletal calcium is a risk factor for osteoporosis and fractures especially of the spine and proximal femur. As the population ages, this becomes an increasingly prevalent situation. It is the source of excessive morbidity and mortality. In the United States alone there are 10 million individuals with osteoporosis and another 34 million who suffer from low bone density. 1 The majority of therapies are pharmacologically based and often require that the patient must take a medication for decades. These drugs have potentially serious adverse effects and many patients do not respond beneficially. The exact etiology of these conditions of dysfunctional calcium metabolism is not fully understood. The optimal therapeutic approach is not clear either. Hence, it would be desirable to find a nutrient-based approach that can help preserve bone mass with fewer adverse effects.2,3,4,5,6,7

Similar to the effects of falling estrogen levels, chronic metabolic acidosis (CMA) has a well-established potential for producing a catabolic effect upon bone. In addition to renal phosphate wasting, experimentally induced CMA also results in hypercalciuria and negative calcium balance attributable to calcium efflux from bone. 8,9,10,11 The modern Western-type diet has been implicated as a cause of life-long mild CMA with secondary bone catabolism caused by the generation of an obligatory daily acid load due largely to endogenous oxidation of cationic and sulfur containing amino acids. 12,13 Although still within the broad range of normal values, plasma bicarbonate concentration decreases progressively when endogenous acid production is increased by dietary changes in normal subjects. 14 CMA directly stimulates the net calcium efflux from bone through both physicochemical and cell-mediated mechanisms. 15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41 Acidosis has multiple effects on cells, one of which is to increase levels of prostaglandins in a variety of systems. 42,43,44,45 In osteoblasts, prostaglandin production is mediated primarily by cyclooxygenase-2 (COX-2). Elevation of prostaglandin levels, especially PGE2, is associated with calcium egress from bone.

Based upon these observations, a combination of nutrients was formulated that incorporates both alkalinizing properties and COX-2 inhibitory function. It was felt that this product would be safe and might possibly be a useful adjunct in the arena of bone health. To test this hypothesis, a human clinical trial in post-menopausal females was performed.

Material and Methods

Study population

The trial was conducted from August 1, 2006 to January 31, 2007 at the Herbal Research Center in Saco, Maine. From a population of 72 individuals who were solicited via regional advertising, 47 subjects met the inclusion criteria: (1) aged 50-75 years; (2) female; (3) not having osteoporosis; (4) being off calcium and vitamin D supplementation for two weeks; (5) not having taken any drugs that impacted bone metabolism; (6) having otherwise stable health; (7) having passed baseline CMP (comprehensive metabolic panel) testing; (8) having signed informed consent. The protocol was reviewed and approved by the Asentral Human Institutional Review Board (Salisbury, MA). The patients were instructed to maintain an isocaloric diet and their previous eating habits during the study period. All subjects were free to withdraw from the study at any time.

Preparation of sample and treatment

The nutrient formulation contained the following ingredients and was manufactured in accordance with generally accepted manufacturing practices at an approved facility in the United States. The formula contained: KHCO3, NaHCO3, MgCO3, Folic Acid, Vitamin D, Vitamin B5, Turmeric, Basil, Sage, Thyme, and Rosemary. The placebo consisted of cellulose and was packaged in capsules of identical size, shape and appearance. All capsules were sealed to prevent odor discrimination. The dose was one capsule four times per day with meals and at bedtime. The subjects were on either arm of the study for six weeks. There was a rolling enrollment process. Subjects were seen and evaluated every two weeks, were screened for adverse effects, questionnaires were administered and compliance was assessed. If more than 10% of the capsules were not taken the subject was deemed non-compliant and was removed from the study.

Randomization and blindness

All subjects were randomly assigned to one of two groups. The same opaque capsules containing either active product or placebo were administered to the subjects by a research assistant blinded to the contents of the capsules. All subjects were treated in the same fashion.

Assessment

At baseline and after six weeks of treatment, vital signs, weight, and lab testing were performed. The endpoints consisted of: (1) determination of 24-hour urinary calcium per gram of creatinine; (2) BSAP; (3) CTX; (4) OST. Differences between baseline and off study (week 6) values were computed for all subjects and were compared between those on control and active product. All lab draws were morning fasting specimens or 24-hour urine collections from morning to morning. All lab testing was done using commercially available assays.

Statistical analysis

The data were analyzed with SPSS software (version 12.0). Paired t tests were used to examine differences between groups at 0 and 6 weeks. All p values were two-tailed, and the * level of significance was set at 0.05.

Results

Demographics

Tables I and II show the demographic data and clinical profiles at the time of entry into the study. As can be seen, there were no significant differences in the baseline parameters between the two groups. One subject in the control group and one subject in the active product group withdrew for personal reasons. 45 subjects completed the trial.

Figure 1
Table 1: Baseline Characteristics

Figure 2
Table 2: Medical History (%)

Between-group comparison at six weeks

There was no significant difference between groups at six weeks in OST status. Figure I shows a statistically significant (p=0.05) increase in BSAP (1.39 ± 0.47 vs. -0.49 ± 0.88 mcg/L) in the active product group compared to the control group. Figure II shows a statistically significant (p=0.01) fall in CTX (-55.4 ± 23.2 vs. +30.1 ± 23.8 pg/ml) in the active product group. Figure III shows a decrease in urinary calcium/g creatinine ( -55 ± 130 vs. +4 ± 53 mg/g) in the active product group (p=0.07).

Figure 3
Figure 1: Change in Bone-Specific Alkaline Phosphatase (BSAP)

Figure 4
Figure 2: Change in C-Telopeptide (CTX)

Figure 5
Figure 3: Change in 24-Hour Urinary Calcium per gram of Creatinine

Adverse effects

No major adverse effects were noted. Three episodes of mild gastrointestinal upset were noted (2-control, 1-active) which were transient and none necessitated withdrawal from the study.

Discussion

This study characterizes the actions of the nutrient combination on metabolic parameters of bone metabolism. Specifically, BSAP increased and CTX diminished. BSAP is a proxy for bone formation, while CTX is one for bone breakdown. These findings are consistent with a beneficial impact on bone formation and a concurrent decrease in bone breakdown. Since total bone mass is determined by the difference in these indicators, these results suggest a favorable impact on global bone mass.

Examination of evolutionary nutrition provides insight into current aspects of bone health and disease. When analyzed from the perspective of dietary intake and its effect on nutritional acid load, great differences are noted between our “ancestral” diet and current dietary consumption. Day after day, modern food choices expose us to a large acid load throughout our lifetimes. In comparison, Paleolithic diets delivered a neutral, or slightly alkaline, load. 46

In animal models, CMA results in decreased bone calcium content and gravimetrically determined bone mass, decreased wet tissue femur density, accelerated rates of cortical and trabecular bone resorption, and diminished rates of bone formation. 47,48,49,50,51 In vitro studies have demonstrated that metabolic acidosis is a potent stimulator of bone resorption and inhibitor of bone formation. 52,53 In neonatal mouse calvariae, incubation in acidic media leads to an increase in the level of prostaglandin E2 (PGE2). 43 There is a parallel increase in net calcium efflux and PGE2 levels. The inhibition of PGE2 production by indomethacin strongly limits this acidosis-induced bone calcium release. 54 These results suggest that acid-induced, cell-mediated calcium efflux from bone is regulated, at least in part, by an increase in endogenous PGE2 production.

The nutrient combination was formulated based on the observation that both CMA and prostaglandin synthesis, especially PGE2, act sequentially to produce bone catabolism. Ingredients were selected and combined to interfere with this deleterious metabolic cascade. Support for this concept includes investigation of the effect of alkalinizing therapies on bone function. Using the neonatal mouse calvarial model, alkaline therapy caused a decrease in osteoclastic *-glucuronidase release and an increase in osteoblastic collagen synthesis. The role of prostaglandin synthesis is supported by the results of the Rancho Bernardo study which evaluated the relationship between non-steroidal anti-inflammatory (NSAID) drug use and bone mineral density (BMD). Women who used propionic acid NSAIDs had higher BMD at each of five sites. These results remained significant after controlling for known covariates of osteoporosis. 55

The components of the nutrient combination include various alkaline salts and herbal COX-2 inhibitors. These were incorporated to increase proton buffering capacity and COX-2 inhibition. A fall in daily urinary calcium losses was observed in the active product group. On a 24 hour basis they lost 59 mg of calcium per gram of creatinine less than the controls. Since the average 24-hour urinary creatinine loss was 1.3 grams, this translates into a daily calcium savings of 77 mg. Metabolic bone loss occurs slowly over decades. If this daily calcium savings is maintained for two decades it would preserve 562 grams of calcium. Since greater than 99% of the calcium resides within the skeleton, this represents almost half the calcium in the skeleton of a healthy young female! That such a savings is possible is suggested by a three year potassium bicarbonate trial that showed no loss of efficacy of the treatment over time. 56

Conclusion

This study demonstrated that supplementation with a combination of herbs, salts and vitamins were able to significantly improve parameters of calcium metabolism and bone health.

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Author Information

James M. Blum, Ph.D.
University of New England

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