Monthly Archives: April 2014

Urine pH or Acid Excretion Doesn’t Predict Bone Density or Fractures

Abstract

Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study.

The acid-ash hypothesis, the alkaline diet, and related products are marketed to the general public. Websites, lay literature, and direct mail marketing encourage people to measure their urine pH to assess their health status and their risk of osteoporosis. The objectives of this study were to determine whether 1) low urine pH, or 2) acid excretion in urine [sulfate + chloride + 1.8x phosphate + organic acids] minus [sodium + potassium + 2x calcium + 2x magnesium mEq] in fasting morning urine predict: a) fragility fractures; and b) five-year change of bone mineral density (BMD) in adults.
Design: Cohort study: the prospective population-based Canadian Multicentre Osteoporosis Study. Multiple logistic regression was used to examine associations between acid excretion (urine pH and urine acid excretion) in fasting morning with the incidence of fractures (6804 person years). Multiple linear regression was used to examine associations between acid excretion with changes in BMD over 5-years at three sites: lumbar spine, femoral neck, and total hip (n = 651). Potential confounders controlled included: age, gender, family history of osteoporosis, physical activity, smoking, calcium intake, vitamin D status, estrogen status, medications, renal function, urine creatinine, body mass index, and change of body mass index.
There were no associations between either urine pH or acid excretion and either the incidence of fractures or change of BMD after adjustment for confounders.
Urine pH and urine acid excretion do not predict osteoporosis risk.

Fenton TR, Eliasziw M, Tough SC, Lyon AW…
BMC Musculoskelet Disord 2010
PMID: 20459740 | Free Full Text

The evidence to support the acid-ash hypothesis of osteoporosis predominantly comes from studies using changes in urine calcium as the outcome [6,8-12,46], some prospective observational studies [16,18,19,47] and one randomized trial [13]. Although one randomized trial has supported the hypothesis [13], another did not [40]. The randomized trial [13] supporting the hypothesis did not use concealment of allocation, a study quality indicator for randomized studies that is important to avoid bias during the randomization process [48]. Without concealment of allocation, investigators can influence the allocation of individuals into the treatment groups, invalidating the randomization. Trials that do not have concealed allocation can overestimate effectiveness of a therapy [49]. The more recent randomized trial, that concealed allocation, did not reveal any protective effect of either potassium citrate or increased fruit and vegetable consumption on change in BMD [14].

Three previous prospective cohort studies of the hypothesis reported some protective associations between fruit and vegetable, potassium, and/or vitamin C intakes and bone health [16,18,19], and thus may support the hypothesis, while two more recent cohort studies do not support it [50,51]. One of the positive reporting studies did not see a significant protective association for potassium once potential confounders were controlled [16]. Further, it is possible that the associations in agreement with the hypothesis in the cohort studies were due to uncontrolled confounding by estrogen status [19], baseline BMD [16,19], change of weight status during follow-up [18], and/or vitamin D status [16,18,19,47].

Further, three recent meta-analyses of the acid-ash hypothesis do not support the hypothesis. First, a meta-analysis of calcium balance studies, restricted to studies of superior methodology, revealed no association between net acid excretion and calcium balance, in spite of the strong relationship between net acid excretion and urinary calcium [52]. A systematic review and meta-analysis of the effect of protein intake on bone health revealed a small beneficial effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials [53]. Further, the acid-ash hypothesis predicts higher phosphate intakes would be associated with increased urinary calcium and lower calcium balance, but this was not supported by a third recent meta-analysis [54].

Review: Alkaline Diet is Not Supported by Evidence

Abstract

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill’s epidemiologic criteria for causality.

Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill’s criteria.
Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined.
Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis.
A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.

Fenton TR, Tough SC, Lyon AW, Eliasziw M…
Nutr J 2011
PMID: 21529374 | Free Full Text

 

Alkaline Diet is Not Justified

Abstract

Meta-analysis of the effect of the acid-ash hypothesis of osteoporosis on calcium balance.

The acid-ash hypothesis posits that protein and grain foods, with a low potassium intake, produce a diet acid load, net acid excretion (NAE), increased urine calcium, and release of calcium from the skeleton, leading to osteoporosis. The objectives of this meta-analysis were to assess the effect of changes in NAE, by manipulation of healthy adult subjects’ acid-base intakes, on urine calcium, calcium balance, and a marker of bone metabolism, N-telopeptides. This meta-analysis was limited to studies that used superior methodological quality for the study of calcium metabolism. We systematically searched the literature and included studies if subjects were randomized to the interventions and followed the recommendations of the Institute of Medicine’s Panel on Calcium and Related Nutrients for calcium studies. Five of 16 studies met the inclusion criteria. The studies altered the amount and/or type of protein. Despite a significant linear relationship between an increase in NAE and urinary calcium (p < 0.0001), there was no relationship between a change of NAE and a change of calcium balance (p = 0.38; power = 94%). There was no relationship between a change of NAE and a change in the marker of bone metabolism, N-telopeptides (p = 0.95). In conclusion, this meta-analysis does not support the concept that the calciuria associated with higher NAE reflects a net loss of whole body calcium. There is no evidence from superior quality balance studies that increasing the diet acid load promotes skeletal bone mineral loss or osteoporosis. Changes of urine calcium do not accurately represent calcium balance. Promotion of the “alkaline diet” to prevent calcium loss is not justified.

Fenton TR, Lyon AW, Eliasziw M, Tough SC…
J. Bone Miner. Res. Nov 2009
PMID: 19419322

Review: High-Protein + Calcium + Fruit + Veggies is Important for Bone Health

Abstract

Acid diet (high-meat protein) effects on calcium metabolism and bone health.

Update recent advancements regarding the effect of high-animal protein intakes on calcium utilization and bone health.
Increased potential renal acid load resulting from a high protein (intake above the current Recommended Dietary Allowance of 0.8 g protein/kg body weight) intake has been closely associated with increased urinary calcium excretion. However, recent findings do not support the assumption that bone is lost to provide the extra calcium found in urine. Neither whole body calcium balance is, nor are bone status indicators, negatively affected by the increased acid load. Contrary to the supposed detrimental effect of protein, the majority of epidemiological studies have shown that long-term high-protein intake increases bone mineral density and reduces bone fracture incidence. The beneficial effects of protein such as increasing intestinal calcium absorption and circulating IGF-I whereas lowering serum parathyroid hormone sufficiently offset any negative effects of the acid load of protein on bone health.
On the basis of recent findings, consuming protein (including that from meat) higher than current Recommended Dietary Allowance for protein is beneficial to calcium utilization and bone health, especially in the elderly. A high-protein diet with adequate calcium and fruits and vegetables is important for bone health and osteoporosis prevention.

Cao JJ, Nielsen FH
Curr Opin Clin Nutr Metab Care Nov 2010
PMID: 20717017

High-Protein Short-Term Diets are Not Detrimental to Bone

Abstract

Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized controlled trial.

Although consuming dietary protein above current recommendations during energy deficit (ED) preserves lean body mass, concerns have been raised regarding the effects of high-protein diets on bone health. The objective was to determine whether calcium homeostasis and bone turnover are affected by high-protein diets during weight maintenance (WM) and ED.

In a randomized, parallel-design, controlled trial of 32 men and 7 women, volunteers were assigned diets providing protein at 0.8 [Recommended Dietary Allowance (RDA)], 1.6 (2 × RDA), or 2.4 (3 × RDA) g · kg(-1) · d(-1) for 31 d. Ten days of WM preceded 21 d of ED, during which total daily ED was 40%, achieved by reduced dietary energy intake (∼30%) and increased physical activity (∼10%). The macronutrient composition (protein g · kg(-1) · d(-1) and % fat) was held constant from WM to ED. Calcium absorption (ratio of (44)Ca to (42)Ca) and circulating indexes of bone turnover were determined at day 8 (WM) and day 29 (ED).
Regardless of energy state, mean (±SEM) urinary pH was lower (P < 0.05) at 2 × RDA (6.28 ± 0.05) and 3 × RDA (6.23 ± 0.06) than at the RDA (6.54 ± 0.06). However, protein had no effect on either urinary calcium excretion (P > 0.05) or the amount of calcium retained (P > 0.05). ED decreased serum insulin-like growth factor I concentrations and increased serum tartrate-resistant acid phosphatase and 25-hydroxyvitamin D concentrations (P < 0.01). Remaining markers of bone turnover and whole-body bone mineral density and content were not affected by either the protein level or ED (P > 0.05).
These data demonstrate that short-term consumption of high-protein diets does not disrupt calcium homeostasis and is not detrimental to skeletal integrity.

Cao JJ, Pasiakos SM, Margolis LM, Sauter ER…
Am. J. Clin. Nutr. Feb 2014
PMID: 24284444

Review: Protein Benefits for Bone may Require Calcium

Abstract

Dietary protein is beneficial to bone health under conditions of adequate calcium intake: an update on clinical research.

To underscore recent clinical studies, which evaluate the association between dietary protein and bone health.
Epidemiologic studies show greater protein intake to be beneficial to bone health in adults. In addition, randomized controlled trials show that protein’s positive effect on bone health is augmented by increased calcium intake. The relation between dietary protein and fracture risk is unclear. Dietary protein may positively impact bone health by increasing muscle mass, increasing calcium absorption, suppressing parathyroid hormone, and augmenting insulin-like growth factor 1 production; but the effects of other factors that contribute to this association, such as dietary protein dose and timing response, require further research.
The positive effects of protein intake on bone health may only be beneficial under conditions of adequate calcium intake. Dietary protein’s relation with fracture risk requires further investigation.

Mangano KM, Sahni S, Kerstetter JE
Curr Opin Clin Nutr Metab Care Jan 2014
PMID: 24316688

Review: Protein has a Small Benefit on Bone Health

Abstract

Dietary protein and bone health: a systematic review and meta-analysis.

There has been a resurgence of interest in the controversial relation between dietary protein and bone health.
This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults.
The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded.
In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD.
A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.

Darling AL, Millward DJ, Torgerson DJ, Hewitt CE…
Am. J. Clin. Nutr. Dec 2009
PMID: 19889822 | Free Full Text

Review: Protein Restriction Potentially Dangerous for Bone Health

Abstract

Dietary protein and skeletal health: a review of recent human research.

Both dietary calcium and vitamin D are undoubtedly beneficial to skeletal health. In contrast, despite intense investigation, the impact of dietary protein on calcium metabolism and bone balance remains controversial. A widely held view is that high intakes of animal protein result in increased bone resorption, reduced bone mineral density, and increased fractures because of its ability to generate a high fixed metabolic acid load. The purpose of this review is to present the recent or most important epidemiological and clinical trials in humans that evaluated dietary protein’s impact on skeletal health. Many epidemiological studies have found a significant positive relationship between protein intake and bone mass or density. Similarly, isotopic studies in humans have also demonstrated greater calcium retention and absorption by individuals consuming high-protein diets, particularly when the calcium content of the diet was limiting. High-protein intake may positively impact bone health by several mechanisms, including calcium absorption, stimulation of the secretion of insulin-like growth factor-1, and enhancement of lean body mass. The concept that an increase in dietary protein induces a large enough shift in systemic pH to increase osteoclastic bone resorption seems untenable.
Recent epidemiological, isotopic and meta-analysis studies suggest that dietary protein works synergistically with calcium to improve calcium retention and bone metabolism. The recommendation to intentionally restrict dietary protein to improve bone health is unwarranted, and potentially even dangerous to those individuals who consume inadequate protein.

Kerstetter JE, Kenny AM, Insogna KL
Curr. Opin. Lipidol. Feb 2011
PMID: 21102327

High-Protein Meat Diet has No Adverse Effects on Bone in Postmenopausal Women

Abstract

A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting markers of bone resorption or formation in postmenopausal women.

Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants’ serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.

Cao JJ, Johnson LK, Hunt JR
J. Nutr. Mar 2011
PMID: 21248199 | Free Full Text

The present study detected no change in potential biomarkers of osteoclast activity, such as blood TRAP, CTX, and sRANKL and urinary DPD, or biomarkers of osteoblast activity, such as blood OPG and OC. The observed changes in IGF-I and PTH were apparently insufficient to elicit detectable changes in biomarkers of osteoclast or osteoblast activity.

Many epidemiological observations have shown that long-term protein intakes are positively associated with bone mineral density (9, 11, 13, 53). Several recent meta-analyses have concluded that protein is beneficial to bone health (54) and protein-induced acid load does not promote skeletal bone mineral loss or contribute to the development of osteoporosis (55, 56). The results from this study are in agreement with those findings.

In conclusion, in postmenopausal women, a diet high in both protein and PRAL increased Ca absorption, at least partially compensating for an increase in urinary excretion. No change in either bone resorption or formation biomarkers was observed, indicating that a high-protein diet is not detrimental. However, the increased serum IGF-I combined with decreased serum PTH concentrations suggest that a high-protein diet could be beneficial to bone health.

Review: Animal Protein Not Inferior or Superior to Vegetable Protein

Abstract

The interaction between dietary protein and bone health.

The role of dietary protein in bone health has been controversial. On the one hand, a plentiful supply of dietary amino acids has been considered important to support bone remodeling while on the other hand there have been concerns that the dietary acid load associated with protein consumption promotes hypercalciuria and loss of bone calcium stores. This article reviews the effect of dietary protein on bone mass and bone density, and the effect on markers of bone resorption and formation and also on fracture risk, looking at both cross-sectional and longitudinal studies and examining both meat and vegetable protein including soy and milk basic protein. The results are not entirely consistent and suggest that the interaction between dietary protein and other components in a mixed diet, such as calcium intake and vegetables and fruit to neutralize acid, are important and may determine whether high-protein diets are beneficial to bone health. Overall the results suggest that dietary protein has a modest beneficial effect on bone markers and bone density. This effect has yet to be consistently linked to reduced fracture risk, probably because of the role of other etiological factors such as the risk of falls. There is not enough evidence currently to suggest that animal protein is superior or inferior to vegetable protein, or that milk or soy protein, respectively, is more favorable than other protein sources.

Jesudason D, Clifton P
J. Bone Miner. Metab. Jan 2011
PMID: 20972896