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Assaying fracture risk with whey

Dairy products have been exalted as premier food and bioactive sources for promoting enhanced skeletal health. One fraction present in bovine whey, known as milk basic protein (MBP), has been the focus of intense investigation, primarily among Japanese researchers, in collaboration with Snow Brand Milk Products (assignee of several international MBP patents and patents pending). MBP contains a number of characterised proteins and peptides, including lactoferrin, lactoperoxidase and cystatin C.

The first study to demonstrate the efficacy of MBP in vivo involved feeding mature ovari-ectomised female rats (the rodent equivalent of surgical removal of the ovaries in women, with attendant deficiency of oestrogens) diets enriched with two different concentrations of MBP, or a control diet, and assessing bone resorption and breaking strength.1 Seventeen weeks of feeding the various diets revealed a significant attenuation of bone loss (femur), and greater retention of bone strength, in the group receiving the higher MBP diet. Additional in vitro experiments suggested that MBP exerted a direct anti-resorptive effect upon osteoclasts. These findings fostered a series of clinical trials in a variety of populations.

MBP, one fraction present in bovine whey, has been the focus of intense investigation

The first clinical investigation with MBP randomised 33 young, premenopausal (average age 28.8 years) women to receive either a flavoured and sweetened, lactic acid-containing beverage once daily, with or without 40mg whey-derived MBP for six months. 2 Bone mineral density (BMD) in the left heel bone was significantly greater after six months in the group receiving the MBP beverage, unattended by any apparent difference in dietary mineral intake over the duration.

A second study (open label, uncontrolled) assigned 30 young men (average age 36.2 years) to receive a similar beverage as in the aforementioned study, yet supplemented with 300mg whey-derived MBP for 16 days.3 Biochemical markers of bone turnover were reduced while markers of bone accretion were increased after 16 days of ingesting the beverage, with no apparent effect upon urinary calcium retention.

A later study randomised 32 menopausal women (average age 50.5 years) to receive a similar whey (40mg MBP) or placebo beverage daily for six months.4 This less-than-rigorous study failed to report on the endocrine or menstrual status in the women examined, although women on hormone replacement therapy were excluded. After six months, the gain in lumbar spine BMD was reported to be significantly greater in the MBP group, with the placebo group showing a net loss, again with no apparent difference in nutrient intake.

The most recent study with MBP randomised 35 young, premenopausal women (average age 21.3 years) to receive either the same MBP beverage (40mg/day) or placebo.5 Lumbar BMD was significantly greater in the MBP group after six months of daily supplementation with the MBP drink.

These studies suggest that bovine whey-derived MBP has notable promise in both promoting peak bone mass and arresting bone loss associated with oestrogen decline. The osteoactive constituents present in MBP remain enigmatic, and likely are due to an interplay of several peptide/growth factors. Very recent work suggests that a product of the digestion of a high molecular weight protein present in MBP exerts bone growth-promoting actions in vitro. 6 This smaller peptide may be generated de novo in human digestion, yielding an orally active osteoactive peptide. More rigorously controlled studies are needed to explore the promise of MBP as a very low-dose complement to calcium-rich foods, beverages and supplements.

Anthony Almada is president and chief scientific officer of IMAGINutrition. Respond: [email protected]

1. Toba Y, et al. Milk basic protein: a novel protective function of milk against osteoporosis. Bone 2000;27:403-8.
2. Aoe S, et al. Controlled trial of the effects of milk basic protein (MBP) supplementation on bone metabolism in healthy adult women. Biosci Biotechnol Biochem 2001;65:913-8.
3. Toba Y, et al. Milk basic protein promotes bone formation and suppresses bone resorption in healthy adult men. Biosci Biotechnol Biochem 2001;65:1353-7.
4. Aoe S, et al. A controlled trial of the effect of milk basic protein (MBP) supplementation on bone metabolism in healthy menopausal women. Osteoporos Int 2005;16:2123-8.
5. Uenishi K, et al. Milk basic protein increases bone mineral density and improves bone metabolism in healthy young women. Osteoporos Int (in press).
6. Yamamura J-I, et al. The fragments of bovine high molecular weight kininogen promote osteoblast proliferation in vitro. J Biochem (in press).

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