Tag Archives: note

Berberine Impairs Muscle Growth and Energy

Abstract

Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine.

Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses.
We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism.
Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented.
Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.

Wang H, Liu D, Cao P, Lecker S…
Diabetes Aug 2010
PMID: 20522589 | Free Full Text

If this study is correct, it is damning for Berberine!

TMG No Benefit for Bones in Homocystinuria

Abstract

The effect of oral betaine on vertebral body bone density in pyridoxine-non-responsive homocystinuria.

Five pyridoxine-non-responsive homocystinuric patients aged 5 to 32 years were treated with oral betaine, 3 g b.i.d, in a double-blind, placebo-controlled, two-year crossover study of its effect on bone mineralization. Betaine therapy significantly reduced mean plasma homocystine (36 +/- 9 (SEM) mumol L-1 to 9 +/- 4 mumol L-1), with variable increases in plasma methionine and no adverse effects. Bone density, measured by computerized tomographic scanning of vertebral bodies, was below normal in all patients at the start of the study, and was not significantly altered by betaine therapy administered according to this protocol.

Gahl WA, Bernardini I, Chen S, Kurtz D…
J. Inherit. Metab. Dis. 1988
PMID: 3148071

Why is this interesting? It’s interesting because several studies show an association between homocysteine and osteoporosis. TMG is known to lower homocysteine. Yet, in this study, there was no increase in bone density despite homocysteine being cut 75%.

FOS + Genistin Increases Bone Density in Rats

Abstract

Combination of genistin and fructooligosaccharides prevents bone loss in ovarian hormone deficiency.

We have reported that soy isoflavones are capable of preventing loss of bone mineral density (BMD) in rats due to ovariectomy. The intestinal microflora is important in rendering soy isoflavones bioavailability by facilitating their conversion to equol. Hence, substances that can modulate the intestinal microflora could affect the bioavailability of isoflavones. The purpose of this study was to examine whether combination of genistin and fructooligosaccharides (FOS), a prebiotic, can enhance the effects of soy isoflavones on bone in ovariectomized (OVX) female rats. Forty-eight 90-day-old female Sprague-Dawley rats were either sham-operated (Sham; one group) or Ovx (three groups) and were placed on dietary treatment for 50 days. The Sham and one Ovx group received a control diet, and the remaining Ovx groups received genistin-rich isoflavones diet (Ovx+G) or genistin-rich isoflavones and FOS diet (Ovx+G+FOS). After 50 days, blood and bone specimens were collected for analysis. The genistin-rich isoflavones diet was able to significantly increase the whole-body, right femur, and fourth lumbar BMD by 1.6%, 1.48%, and 1.3%, respectively in comparison with the Ovx control. The combination of genistin-rich isoflavones diet and 5% FOS further increased whole-body, right femur, and fourth lumbar BMD more compared to the genistin-rich isoflavones diet. Our findings suggest that although a genistin-rich isoflavones diet can increase the BMD in rats with Ovx-induced bone loss, combination of genistin-rich isoflavones and FOS had greater effect in preventing bone loss in this rat model.

Hooshmand S, Juma S, Arjmandi BH
J Med Food Apr 2010
PMID: 20132047

According to Wikipedia, Genistin should be converted to Genistein when ingested.

FOS + Inulin Increase Calcium Absorption and Bone Parameters in Rats

Abstract

Nondigestible oligosaccharides increase calcium absorption and suppress bone resorption in ovariectomized rats.

Nondigestible oligosaccharides (NDO) including inulin and fructooligosaccharides (FOS) have been reported to stimulate calcium absorption. Here we report the effect of a mixture of inulin and FOS (Raftilose Synergy 1, Orafti) on calcium and bone metabolism in ovariectomized (OVX) rats. OVX rats (6 mo old) were fed a semipurified diet for 3 mo in our animal care laboratory for stabilization after ovariectomy. They were then divided into two groups (n = 13/group) and fed either a control or a NDO-supplemented diet (55 g/kg) for 21 d. Catheters were placed in their jugular veins. After 2 d, a tracer ((45)Ca) was administered by gavage or i.v. and blood was sampled for up to 300 min. Urine and fecal samples were collected for 4 d after (45)Ca administration. Femurs were measured for bone mineral density (BMD), breaking strength, and total calcium. Calcium absorption, femoral calcium content, BMD, and bone balance (V(bal)) were significantly increased (P < 0.05) by NDO, whereas the bone resorption rate relative to the bone formation rate was significantly depressed by NDO. We conclude that feeding NDO at 5.5 g/100 g for 21 d has a positive effect on calcium absorption and retention in ovariectomized rats.

Zafar TA, Weaver CM, Zhao Y, Martin BR…
J. Nutr. Feb 2004
PMID: 14747679 | Free Full Text

Note, unfortunately, there was no improvement in breaking strength.

Biking May Help Bones Affected by High Cortisol

Abstract

Effect of physiological exercise on osteocalcin levels in subjects with adrenal incidentaloma.

In the present study, we have evaluated whether physical exercise affect low osteocalcin concentrations observed in patients with subclinical hypercortisolism.
Sixteen patients (10 men and 6 women, age 38-55 yr) with adrenal incidentaloma were studied. Fifteen healthy volunteers matched for age (range 35-47 yr) were used as controls. Subjects were submitted to a 8-week exercise-training program with cycle-ergometer for 1 h/day 3-4 days/week at 60% of their individual VO2 max. Before and after this period, resting venous serum osteocalcin and GH concentrations were measured in the same batch. The blood sampling after 8 weeks of the training program were performed after resting for one day. All patients and controls underwent also the following endocrine evaluation: serum cortisol, plasma ACTH.
Our results demonstrate a significant increase of osteocalcin after physical exercise and a positive correlation between osteocalcin and GH. This later might suggest a role of GH in the increased osteocalcin secretion.
The data of the present study suggest a positive effect of physical exercise on bone metabolism in patients with adrenal incidentaloma.

Coiro V, Volpi R, Cataldo S, Magotti MG…
J. Endocrinol. Invest. Apr 2012
PMID: 22652825

It is surprising the exercise helped considering the form of exercise was cycling – a non-weight bearing exercise.

No Bone Benefit in Young Healthy Women from 3 Months Resistance Training or Protein

Abstract

Effects of resistance training and protein supplementation on bone turnover in young adult women.

The strength of aging bone depends on the balance between the resorption and formation phases of the remodeling process. The purpose of this study was to examine the interaction of two factors with the potential to exert opposing influences on bone turnover, resistance exercise training and high dietary protein intake. It was hypothesized that resistance training by young, healthy, untrained women with protein intakes near recommended levels (0.8 g.kg(-1).d(-1)) would promote bone formation and/or inhibit bone resorption, and that subsequent supplementation to provide 2.4 g protein.kg(-1).d(-1) would reverse these effects.
Bone formation was assessed with serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and bone resorption with urinary calcium and deoxypyridinoline (DPD). Biochemical, strength, anthropometric, dietary, and physical activity data were obtained from 24 healthy, untrained, eumenorrheic women (18-29 y) at baseline, after eight weeks of resistance training (3 d.wk(-1), approximately 1 hr.d(-1); 3 sets, 6-10 repetitions, 13 exercises, 75-85% maximum voluntary contraction), and after 12 weeks of resistance training and 10 days of protein/placebo supplementation. Subjects were randomized (double-blind) to either a high protein (HP) or training control (TC) group and, during the final 10 days, consumed either enough purified whey protein to bring daily protein intake to 2.4 g.kg(-1).d(-1), or an equivalent dose of isoenergetic, carbohydrate placebo.
Strength, lean tissue mass, and DPD increased significantly in both groups over time, while percent body fat and BAP decreased (repeated measures ANOVA, p < or = 0.05, Bonferroni correction). No significant changes were observed for serum OC or urinary calcium, and no significant group (TC, HP) x time (baseline, week 8, week 12) interactions emerged for any of the biochemical measures.
(1) Twelve weeks of high-intensity resistance training did not appear to enhance bone formation or inhibit bone resorption in young adult women, as assessed by biochemical markers of bone metabolism. (2) Subsequent maintenance of a high protein intake for 10 days in these regularly-training, calcium-replete women also showed no effects on bone metabolism.

Mullins NM, Sinning WE
Nutr Metab (Lond) Aug 2005
PMID: 16098231 | Free Full Text

The results are surprising. The full study is available using the link above. The authors note that these women were taking calcium supplements.

…to exclude the potential effects of calcium deficiency, each subject was given a supply of calcium supplements … to begin consuming for the duration of the study. Each was instructed to carry the calcium tablets in her purse or backpack, and was regularly reminded to consume one 500-mg tablet, twice per day.

There may not have been much more bone enhancement to gain.

…the subjects were healthy, eumenorrheic, calcium-replete women, regularly participating in high-intensity exercise.

They measured alkaline phosphatase, serum osteocalcin, urinary calcium. and urinary deoxypyridinoline.

It is possible that other biomarkers may have produced different results, and that, given a longer time frame, bone densitometry could detect osteogenic effects.

 

Calcium and Exercise in Rats

Abstract

Short- and long-term effects of calcium and exercise on bone mineral density in ovariectomized rats.

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n 110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX-EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX-Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX-EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0.05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgroups of animals, showing a decrease of AP and TRAP levels in the younger animals with no significant variations in markers of bone remodelling in the older female rats compared with their respective OVX group.

Gala J, Díaz-Curiel M, de la Piedra C, Calero J
Br. J. Nutr. Oct 2001
PMID: 11591240

I don’t know what to make of this.

HRT + Exercise No Benefit Over HRT Alone

Abstract

Effects of exercise training on bone remodeling, insulin-like growth factors, and bone mineral density in postmenopausal women with and without hormone replacement therapy.

The purpose of this study was to determine the effects of 12 months of weight bearing and resistance exercise on bone mineral density (BMD) and bone remodeling (bone formation and bone resorption) in 2 groups of postmenopausal women either with or without hormone replacement therapy (HRT). Secondary aims were to characterize the changes in insulin-like growth factors-1 and -2 (IGF-1 and -2) and IGF binding protein 3 (IGFBP3) in response to exercise training. Women who were 3-10 years postmenopausal (aged 40-65 years) were included in the study. Women in the HRT and no HRT groups were randomized into the exercise intervention, resulting in four groups: (1) women not taking HRT, not exercising; (2) those taking HRT, not exercising; (3) those exercising, not taking HRT; and (4) women exercising, taking HRT. The number of subjects per group after 1 year was 27, 21, 25, and 17, respectively. HRT increased BMD at most sites whereas the combination of exercise and HRT produced increases in BMD greater than either treatment alone. Exercise training alone resulted in modest site-specific increases in BMD. Bone remodeling was suppressed in the groups taking HRT regardless of exercise status. The bone remodeling response to exercise training in women not taking HRT was not significantly different from those not exercising. However, the direction of change suggests an elevation in bone remodeling in response to exercise training, a phenomenon usually associated with bone loss. No training-induced differences in IGF-1, IGF-2, IGF-l:IGF-2 (IGF-1 : IGF-2), and IGFBP3 were detected.

Milliken LA, Going SB, Houtkooper LB, Flint-Wagner HG…
Calcif. Tissue Int. Apr 2003
PMID: 12574871

What kind of exercise where they doing?

Chocolate Bad for Bones

Abstract

Chocolate consumption and bone density in older women.

Nutrition is important for the development and maintenance of bone structure and for the prevention of osteoporosis and fracture. The relation of chocolate intake with bone has yet to be investigated.
We investigated the relation of chocolate consumption with measurements of whole-body and regional bone density and strength.
Randomly selected women aged 70-85 y (n=1460) were recruited from the general population to a randomized controlled trial of calcium supplementation and fracture risk. We present here a cross-sectional analysis of 1001 of these women. Bone density and strength were measured with the use of dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography. Frequency of chocolate intake was assessed with the use of a questionnaire and condensed into 3 categories: or=1 time/d.
Higher frequency of chocolate consumption was linearly related to lower bone density and strength (P<0.05). Daily (>or=1 times/d) consumption of chocolate, in comparison to Older women who consume chocolate daily had lower bone density and strength. Additional cross-sectional and longitudinal studies are needed to confirm these observations. Confirmation of these findings could have important implications for prevention of osteoporotic fracture.

Hodgson JM, Devine A, Burke V, Dick IM…
Am. J. Clin. Nutr. Jan 2008
PMID: 18175753 | Free Full Text

This is disappointing. Cocoa is normally so healthy. My first thought was that they may be seeing the effects of sugar. Reading the full study, which is available for free using the link above, the authors made these comments:

Chocolate is usually also rich in sugar and contains the methylxanthines, theobromine and caffeine (27), and oxalate (11, 12)….

Oxalate is a potent inhibitor of calcium absorption (13). Furthermore, a single 100-g dose of dark chocolate was found to increase calcium excretion by 147% (14). The basis for this is not clear, but it is likely to include an effect of sugar to increase urinary calcium excretion (14, 15), dependent in part on an increase in plasma insulin that itself stimulates calciuria (29).

I wonder what would happen if you consumed a very dark chocolate (so very low in sugar) and supplemented calcium and vitamin D? The idea being that the very dark chocolate would avoid most of the sugar, and the calcium and vitamin D would hopefully overcome the reduced calcium absorption.

Olive Oil, but Not Nuts, May Protect Bones

Abstract

A Mediterranean diet enriched with olive oil is associated with higher serum total osteocalcin levels in elderly men at high cardiovascular risk.

The intake of olive oil has been related to the prevention of osteoporosis in experimental and in in vitro models. Very few prospective studies have evaluated the effects of olive oil intake on circulating osteocalcin (OC) in humans.
The objective of the study was to examine the longitudinal effects of a low-fat control diet (n=34), a Mediterranean diet enriched with nuts (MedDiet+nuts, n=51), or a Mediterranean diet enriched with virgin olive oil (MedDiet+VOO, n=42) on circulating forms of OC and bone formation markers in elderly men at high cardiovascular risk.
Longitudinal associations between baseline and follow-up (2 yr) measurements of total OC, undercarboxylated osteocalcin, C-telopeptide of type I collagen, and procollagen I N-terminal propeptide (P1NP) concentrations were examined in 127 elderly men randomized to three healthy dietary interventions.
Baseline characteristics (age, body mass index, waist circumference, lipid profile, fasting insulin levels, and bone formation and resorption markers) were similar in all intervention groups. The total osteocalcin concentration increased robustly in the MedDiet+VOO group (P=0.007) in parallel to increased P1NP levels (P=0.01) and homeostasis model assessment-β-cell function (P=0.01) but not in subjects on the MedDiet+nuts (P=0.32) or after the control diet (P=0.74). Interestingly, the consumption of olives was associated positively with both baseline total osteocalcin (r=0.23, P=0.02) and the 2-yr osteocalcin concentrations (r=0.21, P=0.04) in the total cohort.
Consumption of a Mediterranean diet enriched with virgin olive oil for 2 years is associated with increased serum osteocalcin and P1NP concentrations, suggesting protective effects on bone.

Fernández-Real JM, Bulló M, Moreno-Navarrete JM, Ricart W…
J. Clin. Endocrinol. Metab. Oct 2012
PMID: 22855341

Interestingly, nuts did not show a benefit.