Maternal supplementation with dietary arachidonic and docosahexaenoic acids during lactation elevates bone mass in weanling rat and guinea pig offspring even if born small sized.

Whether post-natal long chain polyunsaturated fatty acids (LCPUFA) elevates bone mineral content (BMC) of small and normal neonates was studied using pregnant rats and guinea pigs fed a control (C) diet or low protein (LP) diet to induce small neonates followed by C or LCPUFA diets during lactation. Measurements (days 3 and 21 post-partum) included BMC and density (BMD) plus bone metabolism. In rats LP reduced birth weight but at day 21 elevated weight and whole body BMC; LCPUFA enhanced spine BMC, tibia BMC and BMD and whole body BMD. In guinea pig pups, at days 3 and 21, LP reduced weight, whole body and regional BMC and BMD whereas LCPUFA reduced day 3 osteocalcin and elevated day 21 spine BMD. LCPUFA minimized loss of whole body BMC in dams and elevated osteocalcin in sows. LCPUFA during lactation enhances bone in normal and small neonates without compromising maternal bone.

Bone mass in First Nations, Asian and white newborn infants.

OBJECTIVE: To compare bone mass in newborn infants of First Nations, white and Asian mothers while accounting for vitamin D status. Fifty infants born healthy at term age were measured for bone mass using dual energy x-ray absorptiometry (DXA) within 15 days of life. Vitamin D status was measured as 25(OH)D in cord plasma. White infants were separated based on 25(OH)D concentrations into sufficient and insufficient (< 32.5 nmol/L) to match for vitamin D status of the Asian infants and the First Nations group. Differences among groups were tested using ANOVA and post hoc testing with Bonferroni multiple comparisons test. There were no differences in whole body, spine or femur BMC between the white sufficient and insufficient infants. However, the Asian infants had lower (P < 0.01) spine BMC compared to the white infants and the First Nations infants were intermediate. No differences among the ethnic groups were observed for whole body or femur BMC. These data suggest that white and First Nations newborn infants have comparable bone mass. Asian infants have lower spine bone mass which is more than a factor of body size and independent of vitamin D status at birth.

Dietary conjugated linoleic acid in the cis-9, trans-11 isoform reduces parathyroid hormone in male, but not female, rats.

Previously, a mixture of conjugated linoleic acid (CLA) isoforms reduced parathyroid hormone (PTH) in male rats over 8 weeks. The objective herein was to determine which isoform caused the reduction in PTH; whether the effect was sex specific; and whether CLA-induced reductions in PTH were sustained. Male and female weanling rats (n=48) were randomized to a control diet or one made with 0.5% of the diet as cis-9, trans-11 (c9,t11) CLA, 0.5% of the diet as trans-10, cis-12 (t10,c12) CLA or these CLA in a mixture. Measurements made after 4, 8 and 16 weeks were body weight, bioactive PTH, ionized Ca, whole-body and regional bone mineral density (BMD) using dual-energy X-ray absorptiometry. With the use of a factorial design, a sexxc9,t11 CLA interaction was observed that reduced PTH (139.5+/-63.9 vs. 95.8+/-42.4 pg/ml, P=.02) in male rats only. No other effects of c9,t11 CLA were observed. Regarding t10,c12 CLA, no interaction effects were observed, but a main effect was observed to reduce lumbar spine BMD (0.265+/-0.044 vs. 0.255+/-0.044 g/cm(2), P<.01) along with reduced retention of Ca and P at Week 4. No other dietary effects were observed. In summary, the c9,t11 CLA isoform is responsible for reduced PTH and this effect is sex specific; this was true whether fed as a pure isomer or mixed with an equal amount of t10,c12 CLA. Whether such reductions in PTH might be observed in females lacking sex hormones such as ovariectomized rats and also in humans is required to expand health implications of dietary CLA.

Minimal enteral feeding within 3 d of birth in prematurely born infants with birth weight < or = 1200 g improves bone mass by term age.

BACKGROUND: Evidence-based practice guidelines for aggressive nutritional intervention by using parenteral amino acids (AAs) and minimal enteral feeding (MEF) as early as the first day of life have not been tested for benefits to bone mass. OBJECTIVE: We investigated whether early introduction of parenteral AAs and MEF improves growth and bone mass achieved by term age in infants born prematurely. DESIGN: Twenty-seven infants who were < or = 1200 g and < or = 32 wk gestation at birth were randomly assigned by using a 2 x 2 design to treatment of either 1 g AAs/kg within the first 24 h or 12 mL MEF x kg(-1) x d(-1) within the first 72 h of life. Nutrition and growth were documented during hospitalization, and bone mineral content (BMC) of lumbar spine 1-4, femur, and whole body was measured at term age. Biomarkers of bone metabolism were measured at weeks 1, 3, and 5 and at discharge. Statistical analysis was conducted by using 2 x 2 analysis of variance for intent to treat and for infants receiving protocol nutrition. RESULTS: Over the first 14 d of life, a main effect of early AAs elevated total intake of protein, and a main effect of early MEF was a higher frequency of MEF volumes exceeding > 12 mL x kg(-1) x d(-1). Main effects on growth were not evident. An interaction effect was observed for osteocalcin whereby early AAs or MEF alone elevated osteocalcin. A main effect of early MEF yielded higher BMC of spine and femur. CONCLUSION: Early aggressive nutrition support with MEF enhances BMC in premature infants, but early MEF or AAs do not improve growth.

Low levels of dietary arachidonic and docosahexaenoic acids improve bone mass in neonatal piglets, but higher levels provide no benefit.

In piglets, feeding arachidonic acid (AA) and docosahexaenoic acid (DHA) in a 5:1 ratio leads to elevated bone mass, but the optimal total quantity requires clarification. We studied bone mass and modeling of piglets that were randomized to receive 1 of 4 formulas for 15 d: control formula or the same formula with various levels of AA:DHA (0.5:0.1 g, 1.0:0.2 g or 2.0:0.4 g AA:DHA/100 g of fat). Measurements included: bone area (BA), mineral content (BMC), and density (BMD) of whole body, lumbar spine, and excised femurs; biomarkers of bone modeling were plasma osteocalcin and urinary cross-linked N-telopeptides of type 1 collagen (NTx), tibial ex vivo release of prostaglandin E(2) (PGE(2)), plasma insulin-like growth factor-1 (IGF-1), and tissue fatty acids. Main effects were identified using ANOVA and post hoc Bonferroni t tests. In supplemented piglets, relations among liver fatty acid proportions and bone mass were assessed using Pearson correlations. Whole body (P = 0.028) and lumbar spine (P = 0.043) BMD were higher in the group supplemented with 0.5:0.1 g AA:DHA/100 g of fat than in controls. Tissue AA and DHA increased in proportion to diet levels. Liver eicosapentaenoic acid (EPA) correlated positively (r > or = 0.38, P < or = 0.05) with whole body and femur BMC and BMD and lumbar spine BMC. Liver AA:EPA ratio correlated negatively (r > or = -0.039, P < or = 0.05) with whole body, femur, and lumbar spine BMC plus whole body and femur BMD. Dietary 1.0:0.2 g AA:DHA/100 g reduced NTx relative to 2.0:0.4 g AA:DHA/100 g of fat (P = 0.039). The diets did not affect the other biochemical variables measured. Low levels of dietary AA:DHA (0.5:0.1 g/100 g of fat) elevate bone mass, but higher amounts are not beneficial.

Dietary soy protein attenuates renal disease progression after 1 and 3 weeks in Han:SPRD-cy weanling rats.

Compared with casein, dietary soy protein slows disease progression in animal models of chronic renal injury. To determine whether dietary soy protein feeding can alter early disease progression, male Han:SPRD-cy rats (n = 87) in a very early stage of chronic kidney disease were fed soy protein compared with casein-based diets for 1 or 3 wk. Kidneys were assessed for fibrosis, cyst growth, fatty acid composition and prostaglandin E(2) (PGE(2)) production. Soy protein feeding significantly reduced renal fibrosis by 22% (P = 0.0347) and 38% (P = 0.0102) after 1 and 3 wk of diet, and cyst growth was 34% lower after 3 wk (P < 0.0001). Kidney 18:2(n-6) levels were reduced in normal and diseased rats after as little as 1 wk of consuming the soy protein diet. Dietary soy protein also partially ameliorated the suppression of PGE(2) production observed in diseased kidneys. Compared with diseased kidneys from casein-fed rats, ex vivo PGE(2) release was 31-32% higher after 1 (P = 0.0281) and 3 (P = 0.0189) wk of dietary soy protein consumption. Hence, the first signs of a beneficial soy protein effect were observed after 1 wk of feeding, with further improvements evident after 3 wk. These data demonstrate that dietary soy protein compared with casein delays disease progression in an early stage of chronic kidney disease.

Dose response of bone mass to dietary arachidonic acid in piglets fed cow milk-based formula.

BACKGROUND: The addition of arachidonic acid (AA) and docosahexaenoic acid (DHA) to infant formula was recently approved in North America. In piglets, dietary AA is linked to elevations in bone mass. OBJECTIVE: The objective was to investigate the effects of varied amounts of dietary AA on bone modeling and bone mass with the use of the piglet model for infant nutrition. DESIGN: Male piglets (n = 32) were randomly assigned to receive 1 of 4 formulas supplemented with AA (0.30%, 0.45%, 0.60%, or 0.75% of fat) plus DHA (0.1% of fat) from days 5 to 20 of life. Measurements included biomarkers of bone modeling, fatty acid status, and whole-body and femur bone mineral content; bone area was measured by dual-energy X-ray absorptiometry. Differences among groups were detected with two-factor analysis of variance. Regression analyses were used to determine factors responsible for bone mineral content after dietary AA was accounted for. RESULTS: Proportions of AA in plasma, liver, and adipose were modified by the dietary treatments, but bone modeling was not affected. Liver AA was positively related to plasma insulin-like growth factor 1 and calcitriol and urinary N-telopeptide. Whole-body bone mineral content was elevated in the piglets fed 0.60% and 0.75% AA and was best predicted by dietary AA and bone resorption. CONCLUSIONS: This study confirms that dietary AA alters bone mass and clarifies the best amount of AA to add to the diet of pigs born at term. Because the amount of dietary DHA was held constant, whether other amounts of DHA are related to bone mass requires investigation.

Dietary arachidonic acid suppresses bone turnover in contrast to low dosage exogenous prostaglandin E(2) that elevates bone formation in the piglet.

This study was designed to compare the effects of dietary arachidonic acid (AA) versus prostaglandin E(2) (PGE(2)) on bone cell metabolism and bone mass. Twenty-eight piglets from 7 litters were randomized to 1 of 4 treatments for 15 days: fatty acid supplemented formula (FA: 0.8% of total fatty acids as AA and 0.1% of total fatty acids as DHA)+PGE(2) injections (0.1mg/kg/day), FA+saline injections, standard formula (STD: n-6:n-3 of 8:1) + PGE(2) injections or STD+saline injections. PGE(2) resulted in elevated osteoblast activity as indicated by plasma osteocalcin and also reduced urinary calcium excretion. Dietary FA resulted in reduced bone resorption as indicated by urinary N-telopeptide and reduced bone PGE(2). Both PGE(2) and FA treatments independently lead to elevated femur mineral content, but the combined treatment caused a reduction. Thus the mechanisms by which PGE(2) and FA lead to enhanced bone mass are distinct.

Modulation of essential (n-6):(n-3) fatty acid ratios alters fatty acid status but not bone mass in piglets.

Dietary (n-6) and (n-3) fatty acids have been implicated as important regulators of bone metabolism. The main objective of this research was to define the response of whole-body growth, fatty acid status and bone mass to a reduced dietary (n-6):(n-3) fatty acid ratio. A secondary objective was to determine whether there is an amount of fat x fatty acid ratio interaction for these outcomes. Piglets (n = 32) were randomized to 1 of 4 diets: group 1: [30 g fat/L + (n-6):(n-3) ratio 4.5:1]; group 2: [30 g fat/L + (n-6):(n-3) ratio 9.0:1]; group 3: [60 g fat/L + (n-6):(n-3) ratio 4.5:1]; and group 4: [60 g fat/L + (n-6):(n-3) ratio 9.0:1]. After 21 d, outcomes assessed included growth, fatty acid status and bone mass and metabolism. Growth and bone mass did not differ among the four groups nor did arachidonic acid (AA as g/100 g fatty acids) in plasma, adipose and brain. Piglets fed diets 1 and 3 with the lower (n-6):(n-3) ratio had lower liver AA (P < 0.001). Those fed diets 1 and 2 containing 30 g fat/L had lower docosahexaenoic acid (DHA as g/100 g fatty acids) in liver (P < 0.001), plasma (P = 0.019) and adipose tissue (P = 0.045). However, piglets fed diets 1 and 3 had higher (P < 0.001) brain DHA than those fed diets with a higher (n-6):(n-3) ratio. Higher plasma DHA was associated with less bone resorption (r = -0.44, P = 0.01). Therefore, elevation of dietary (n-3) fatty acids supports growth and fatty acid status while not compromising bone mass. The results may be of relevance to the nutritional management of preterm infants whose DHA status is often too low and bone resorption too high.