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  1. All, Bone health is a perennial topic of discussion for folks practicing CR. I'm not quite as personally concerned about bone health on CR as I used to be for several reasons: In both humans (Fontana et al. PMID: 20969721) and mice (PMID: 26572927), CR appears to result in lighter, but perhaps not more fracture-prone bones, particularly once body weight is factored in, as we discussed in this thread. I practice both weight bearing exercise (jogging & resistance training) which is known to help build or at least maintain bone health. I practice cold exposure to increase brown adipose tissue (BAT). The amount of BAT tissue a person has is positively and quite strongly correlated with their bone mineral density at all measurement sites, independent of their body weight (PMIDs 22259053 and 24140784) as discussed here. This is particularly encouraging for us skinny folks, since BMD is usually associated with higher weight, but BAT is generally much less prevalent in obese people - suggesting (but obviously not proving...) you can be skinny but still have strong bones as long as you've got BAT. Nevertheless, I still have lingering doubts about the potential negative impact of long-term CR on bone health for my own case and in general. Read this for a scary anecdotal perspective from a former CR practitioner whose osteoporosis made him quit CR and spend a few years in rough shape, trying to build back his bone health. While he acknowledges his diet wasn't optimal, it's still a somewhat troubling story. So with these lingering concerns in the back of my mind, I was quite interested to come across recent evidence on topic germane to bone health that we discussed (and some of us even practiced) many years ago on the CR list, namely vibration therapy. I actually (re)discovered whole body vibration (WBV) therapy accidentally, in my never-ending search for ways to boost BAT. Remarkably, it turns out that WBV boosts BAT levels in rats (PMID 26125027), mice (PMID 25317067) and people (PMID 23423629), as discussed here. It also appears to improve balance, boost leg muscle strength & power, and promote weight & visceral fat loss [1][2]. But perhaps the most interesting and relevant effect of WBV is it's influence on indicators of bone health, specifically bone mineral density (BMD) - a metric whose relevance for CR folks is questionable (given our thinner but not necessarily weaker bones), but which serves as the gold standard for bone health in the medical community. Several individual studies [1][6] as well as systematic reviews [2-5] found that WBV builds bone mass, in some cases as well or better than exercise [2][6]. There was a recent randomized (allegedly placebo controlled!?) trial [7] of WBV therapy in 174 elderly men and women, which only found a non-significant trend towards improved BMD after 24 months of WBV therapy for 10 minutes per day. I seems to me the likely explanation for the disappointing results of [7] tells us something interesting about the right protocol for effective WBV therapy for bone health and other benefits. But first, a little history. Anyone who recalls the ancient CR email list discussion of vibration therapy will remember that the only viable and affordable, DIY option for many of us at the time were massage seat covers like this one - which were really quite pitiful in terms of their ability to create any sort of significant, and therefore effective, vibration. The tiny eccentric rotating mass motors used in this type of massage seat just don't have the mass or the power to create a very strong vibration effect. They might feel soothing, but they aren't likely to build bone mass. So I gave up on this sort of vibrating seat massager as a bone-building therapy years ago. I suspect others did as well. And this sort of lack of vibration power appears to be the explanation for the failure of WBV therapy to result in improved BMD in [7]. In particular [7] used a vibration frequency of 37 Hz, which is in the range shown in other studies to be efficacious, but used a very mild 0.3g vibration magnitude - which is really quite anemic. In fact, the weakness of the vibration may be why they could characterize their study as a placebo-controlled trial, since simply standing on the motionless vibration platform may have not felt much different from turning the machine on for the so-called "active" treatment! In contrast, studies where WBV has proven effective at improving strength, reducing BMI and building BMD used a much more vigorous vibration protocol. For example [1] used a similar, although slightly higher, vibration frequency (40-60hz), but the real difference was in the vibration amplitude. In [1], the vibration plate had a motion range of 2-5mm. That may not sound like much, but at 40-60 Hz, those tiny excursions result in pretty strong G-forces. For example, the manual for the vibration plate I'm now using (see below), says a 2mm, 40Hz vibration pattern results in an acceleration of 6.5g, and a 5mm, 40Hz vibration pattern results in 16.2g acceleration, which are 22x and 54x more vigorous, respectively, than the vibration protocol used in the failed RCT [7]. At the higher end of the vibration frequency used in [1] (i.e. 60Hz rather than 40Hz), the acceleration forces would be even higher. Here are some other protocols detailed in [4] (full text - I highly recommend this paper for anyone interested in pursuing WBV further) that have proven effective: In a study by Verschueren et al. [ref], in which the subjects were exposed to vertical vibrations 3 times per week for 24 weeks (35-40 Hz; 1.7-2.5 mm; 2.28-5.09 g), reported an increase bone mineral density of the femur. [T]he study of the Von Stengel [79], which included 108 postmenopausal women randomly assigned to three groups: 1) pivotal vibration platform (PVT - 12.5 Hz; 12 mm [excursion]), 2) vertical vibration platform (VVT), which had three 15-minute treatments per week (both groups had a magnitude of vibration of 8 g) and 3) control/fitness group which had two low-intensity workouts per week. They came to the conclusion that bone density increased significantly when it comes to the lumbar spine (PVT + 0.7% ± 2.2% and VVT + 0.5% ± 2%), while, when it comes to the femur, progress which was recorded in both vibration groups (PVT + 0.3% ± 2.7% and VVT + 1.1% ± 3.4%) was not statistically significant. The control group’s bone mineral density was decreased in the lumbar spine (-0.4% ± 2%), whilst the femur bone mineral density was maintained at the same level (-0.0% ± 2.1%). The study of Ruan et al. [ref] showed the highest increase in bone mineral density. In fact, after 6 months of 10-minutes, 5 times per week, vibration training at a frequency of 30 Hz and amplitude of 5 mm (overall magnitude 18 g), on a sample of 116 postmenopausal women, these authors recorded an increase in bone mineral density at the lumbar spine by 6.2% and hip by 4.9%, compared to control (n = 50) group. Interestingly, also from [4], comes this encouraging analysis for us skinny folks: Also, noteworthy is that, in that same study, after a post hoc analysis, authors [ref] found statistically significant differences in women with low body weight (<65 kg) as opposed to the heavier ones, where difference was not statistically significant. These authors found that women with lower body weight, in this case, below 65kg, recorded the best effects. Namely, compared to the placebo group, they have achieved a relative benefit in bone mineral density values of 2.1% at femoral neck, 1.92% at trochanter and 3.35% in lumbar spine. Also from [4] comes this discussion of another failed WBV trial whose protocol was apparently too weak: The best proof that the correct determination of the frequencies and amplitudes can be very important can be found in a study by Rubin et al. [ref]. In their study, after 12-month treatment that included daily, 2x10 minutes, vibration training (30 Hz; 0.2 g; 0, 5 μm), authors [49] showed a decrease in bone mineral density in experimental (-0.69%) and placebo (-0.27%) group at femur (-0.69%; -0.27%), the trochanter (-0.07%; -0.19%) and the lumbar spine (-0.51%; -0.65%). Such small differences after this extensive treatment (12 months x 7 days x 2 x 10 min) can be found in the intensity that was not enough to, not only increase the anabolic effects, but also inhibit the resorptive ones. This can be primarily attributed to very small amplitude, which was less than one millimeter. So it looks like WBV therapy can be effective, even in skinny older folks, but at least several G's of acceleration are required for WBV therapy to work. Fortunately, the technology available to consumers at an affordable price today has improved dramatically since the early 2000s when I last pursued vibration therapy with a seat massager. In fact, thanks to Kenton's recommendation (thanks Kenton!), I'm now the proud owner of a vibration plate that hits the sweet spot of the effective WBV protocols described above. It cost $179 on Amazon but shipping from them was extra. So I actually bought it for a couple dollars more on ebay with the advantage of free shipping, saving more than $20 on overall cost. It shipped the same day I ordered it, and arrived quite quickly (3-4 days) considering it's large size - the box was almost 3'x3'x1' and weighed 30-40 lbs. I've been using it now for about a week and really like it. It's quite rugged and I expect it to last. Kenton says he's been using his everyday for about a year. Here is what it looks like based on the manufacturer's image posted to Amazon: It's hard to get a feel for just what it's like and how big it is, from these pictures, so here is one I took of myself standing on it in the posture I've been using: Notice the straps? I think they are designed to help maintain stability. It's quite a weird sensation, and I can imagine someone losing their balance and falling off, particularly if frail. But as a bonus, I find by holding the straps taut, they help to couple my shoulders and back to the vibration, rather than just my legs, thereby (hopefully) increasing the bone-building effects on my spine. As I alluded to, the specs on the machine put it directly in the sweet spot for the therapeutic vibration magnitude observed in the studies cited above. In fact, just like [1], it has an excursion range of either 2 or 5 mm (the 'soft' vs 'strong' settings) and an adjustable frequency of 5 to 42Hz. According to the manual, at 42Hz the plate generates a 7.1g vibration on the 'soft' setting and 17.8g on the 'strong' setting. Quite in line (if not a bit higher) than the studies I cited which found benefits. Subjectively, it's really quite vigorous and downright weird feeling, particularly on the max (17.8g) setting. It's nothing like the very gentle vibration you feel with the kind of seat massager I experimented with previously. I can well imagine this sort of stimulus could have physiological effects. I fact, I've been keeping the sessions brief - only 1-2 minutes once or twice a day. As I understand Kenton uses it in a similar fashion. The vibration is so vigorous in fact, it's worth considering contraindications. Again from review article [4]: Contraindication factors for the use of vibration training, enlisted by the manufacturers themselves [refs] are: the existence of kidney or bladder stones, epilepsy, cancer, pacemaker, recent implantation or surgery, thrombosis, hernia, rheumatologic arthritis, migraine, some cardiovascular problems and spinal injuries. Slatkowska et al. [ref] stated that there is no risk of using vibration training, and that it represents a new, promising modality for improving the characteristics of the skeletal system in postmenopausal women, respectively, same authors stated that the whole body vibration training increases muscular strength and power and slows down bone mineral density loss. Also, Russo et al. [ref] reported that there were no adverse effects of vibration training for women in menopause and post-menopause. The only side effect that was observed was increased itching in the lower extremities, more specifically, 6 of 17 participants, who were included in high magnitude vibration training reported these side effects. Moawed and Mohammed [ref] have explained in their study that the itching that occurs during the first use of the vibrating stimulus is the result of an increase in skin blood flow. In addition, in that same study, knee pain was reported by two obese subjects diagnosed with osteoarthritis, but it withdrew after a few days allowing subjects to continue with the treatment. Besides that, it is noteworthy that some authors [ref] claimed that at frequencies above ~50 Hz severe muscle soreness and even hematoma may emerge in untrained subjects, but this hasn’t been empirically tested due to the ethics issue. Overall, I'm very satisfied with the purchase, and pretty optimistic based on the available evidence that the vibration therapy this machine delivers has the potential to be beneficial for building bones, brown/beige fat, and perhaps even muscle. I think this would be especially true for people who aren't already naturally as active as I am. I'm interested what others think. Kenton, I know you've been using this same machine for a while. Anything you would add? Exactly how are you using the machine (settings, frequency, duration etc)? TomB, I know you're interested in optimizing your time spent exercising. Maybe it would be worth adding a brief bout of vibration therapy to your protocol? James Cain, I asked you about vibration therapy when we were together (in the exercise room!) at the CR Conference. You expressed skepticism about its likely efficacy, but acknowledged you hadn't looked at it too carefully lately. Does any of the evidence presented above change your mind? --Dean ---------- [1] Int J Med Sci. 2013;10(3):307-11. doi: 10.7150/ijms.5161. Epub 2013 Feb 2. Ten-week whole-body vibration training improves body composition and muscle strength in obese women. Milanese C(1), Piscitelli F, Zenti MG, Moghetti P, Sandri M, Zancanaro C. Free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575626/ This work explored the short-term effect of whole body vibration (WBV) training on anthropometry, body composition and muscular strength in obese women. Fifty obese women (age = 46.8 ± 7.81[sD]y; BMI = 35.1 ± 3.55 kg/m(2)) were assigned to a ten-week WBV training period, two times a week (in each session, 14 min vibration training, 5 min rest; vibration amplitude 2.0-5.0mm, frequency 40-60 Hz), with (n = 18) or without (n = 17) radiofrequency, or to a non-exercise control group (n = 15). Subjects were instructed not to change their habitual lifestyle. Before and after the ten-week experimental period, anthropometric measurements, dual-energy X-ray absorptiometry (DXA), and the leg press, leg curl and leg extension strength tests were carried out. All changes in the two groups of WBV training, with or without radiofrequency, were similar and these groups were combined in a single WBV intervention group. As compared to controls, subjects submitted to WBV training had significantly lower BMI, total body and trunk fat, sum of skinfolds and body circumferences. On the other hand, lower limb strength tests were increased in the WBV group. These preliminary results suggest that WBV training may improve body composition and muscular strength in obese women and may be a useful adjuvant to lifestyle prescriptions. PMCID: PMC3575626 PMID: 23423629 ------------ [2] Disabil Rehabil. 2012;34(11):883-93. doi: 10.3109/09638288.2011.626486. Epub 2012 Jan 6. Efficacy of whole body vibration exercise in older people: a systematic review. Sitjà-Rabert M(1), Rigau D, Fort Vanmeerghaeghe A, Romero-Rodríguez D, Bonastre Subirana M, Bonfill X. Author information: (1)Blanquerna School of Health Science, Universitat Ramon Llull, Barcelona, Spain. mercesr@blanquerna.url.edu PURPOSE: The aim of this study was to perform a systematic review of the literature on whole body vibration programs in older population and a meta-analysis of randomized controlled clinical trials. METHOD: A search was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL and PsychINFO databases. We included randomized controlled trials evaluating the efficacy and safety of whole body vibration training in older populations compared to conventional exercise or control groups that assessed balance, muscle strength, falls, bone mineral density and adverse events. RESULTS: Sixteen trials met the inclusion criteria. Comparing the vibration and the control group, we found that vibration significantly improved knee muscle isometric strength (18.30 Nm, 95% CI 7.95-28.65), muscle power (10.44 W, 95% CI 2.85-18.03) and balance control (Tinetti test: 4.5 points, 95% CI 0.95-8.11). Comparison with a conventional exercise showed that the only significant difference was bone mineral density in the femoral neck (0.04 g/cm(-2), 95% CI 0.02-0.07). There were no serious complications in most of studies. CONCLUSION: Whole body vibration training may improve strength, power and balance in comparison with a control group, although these effects are not apparent when compared with a group that does conventional exercise. PMID: 22225483 ----------- [3] Sportverletz Sportschaden. 2014 Sep;28(3):125-31. doi: 10.1055/s-0034-1366545. Epub 2014 May 14. [Does muscle activation during whole-body vibration induce bone density improvement in postmenopausal women?--A systematic review]. [Article in German] Calendo LR(1), Taeymans J(2), Rogan S(2). Author information: (1)Fachhochschule Südschweiz, Departement Graubünden, Landquart, Schweiz. (2)Berner Fachhochschule, Fachbereich Gesundheit, Disziplin Physiotherapie. BACKGROUND: Whole body vibration training (WBV) stimulates muscles by mechanical vibrations. The resulting muscle activity and bone deformation may provoke an increase in bone density. The aim of this systematic review was to evaluate whether muscle activation and muscle strengthening caused by vibration training has an effect on bone density in postmenopausal women. METHODS: This systematic review was conducted according to the guidelines of the PRISMA statement for meta-analyses and systematic reviews. The literature search was conducted in several electronic databases (PubMed und CINAHL) and Google Scholar. The literature search was conducted between June 2012 and August 2013. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool by two independent persons. RESULTS: A total of 246 studies was found. In this present analysis three studies with vertical and two studies with side-alternating WBV were included, totalling 368 participants with an age range between 60.7 and 79.6 years. From those 132 participants trained on vertically while 67 participants trained on side-alternating WBV engines. The included study shows a moderate to high risk of bias. The selected frequencies ranged from 12.0 Hz to 40.0 Hz for vertical WBV and 12.5 Hz for side-alternating WBV. The amplitude ranged between 1.7 and 12.0 mm with an acceleration from 0.1 to 10.0 g. CONCLUSION: This systematic review showed significant influences on the isometric maximal voluntary contraction (IMVC) between 15.1 and 16.5 % and on dynamic maximal strength (DMS) between 7.9 to 16.5 % after vertically WBV (frequencies: 30.0 to 40.0 Hz; 3 sessions per week; 15 minutes per session) and on IMV with 26.6 % (frequency: 12.5 Hz; 3 sessions per week; 15 minutes per session). This increased muscle activity resulted in an improved bone density in the lumbar spine between 0.5 % to 0.7 % and the hip between 0.8 % to 0.9 % in postmenopausal women. These clinically significant findings should be confirmed by a large high-quality randomised controlled trial and reported following the CONSORT Statement guidelines. © Georg Thieme Verlag KG Stuttgart · New York. PMID: 24828509 --------- [4] J Osteopor Phys Act 3:150. (2015) doi:10.4172/2329-9509.1000150 Whole Body Vibration Training Effects on Bone Mineral Density in Postmenopausal Osteoporosis: A Review. Abazovic E, Paušic J, Kovacevic E Free full text: http://www.esciencecentral.org/journals/whole-body-vibration-training-effects-on-bone-mineral-density-inpostmenopausal-osteoporosis-a-review-2329-9509-1000150.php?aid=58099 Abstract Objective: Evaluate long term whole body vibration training effects on bone mineral density in postmenopausal osteoporosis. Background: Osteoporosis has been defined as a skeletal system disease characterized by low bone density and deterioration of bone microarchitecture which results in increased risk for fracture occurrence and predisposes the person to injury. Whole body vibration therapy showed positive effects on Bone mineral density. Materials and methods: Literature and scientific papers review of was conducted through the use of several databases: Science Direct, Web of Science, SCIdirect, PubMed, Taylor and Francis Online, Springer Link, SAE publications, JAMA Pediatr Idea: drexler e-repository and archives, Google Scholar and City Library Marko Marulic Split University Library in Split Online catalog. Conclusion: Whole body vibration training is a relatively new and promising non-pharmacological method for bone mineral density decline prevention. ------ [5] Osteoporos Int. 2010 Dec;21(12):1969-80. doi: 10.1007/s00198-010-1228-z. Epub 2010 Apr 21. Effect of whole-body vibration on BMD: a systematic review and meta-analysis. Slatkovska L(1), Alibhai SM, Beyene J, Cheung AM. Author information: (1)Osteoporosis Program, University Health Network/Mount Sinai Hospital, Toronto, ON, Canada. SUMMARY: Our systematic review and meta-analysis of randomized controlled trials (RCTs) examining whole-body vibration (WBV) effect on bone mineral density (BMD) found significant but small improvements in hip areal BMD (aBMD) in postmenopausal women and in tibia and spine volumetric BMD in children/adolescents, but not in other BMD measurements in postmenopausal women and young adults. INTRODUCTION: Animal experiments report anabolic bone changes in response to WBV, but data in humans are limited. Our objective is to conduct a systematic review and meta-analysis of RCTs examining WBV effect on BMD. METHODS: Eligible RCTs included randomized or quasi-randomized trials, with follow-up of ≥ 6 months, examining WBV effects on BMD in ambulatory individuals without secondary causes of osteoporosis. The weighted mean differences between WBV and control groups in absolute pre-post change in spine and hip aBMD, and in spine and tibia trabecular volumetric BMD (vBMD) were calculated. RESULTS: eight RCTs in postmenopausal women (five RCTs), young adults (one RCT), and children and adolescents (two RCTs) were included. The regimens were heterogeneous, study durations were relatively short, and available data was mostly per-protocol. In postmenopausal women, WBV was found to significantly increase hip aBMD (0.015 g cm(-2); 95% confidence interval (CI), 0.008-0.022; n = 131) versus controls, but not spine aBMD (n = 181) or tibia trabecular vBMD (n = 29). In young adults, WBV did not increase spine or hip bone mineral content, or tibia trabecular vBMD (n = 53). In children and adolescents, WBV significantly increased spine (6.2 mg cm(-3); 95% CI, 2.5-10.0; n = 65) and tibia (14.2 mg cm(-3); 95% CI, 5.2-23.2; n = 17) trabecular vBMD. CONCLUSIONS: We found significant but small improvements in BMD in postmenopausal women and children and adolescents, but not in young adults. WBV is a promising new modality, but before recommendations can be made for clinical practice, large-scale long-term studies are needed to determine optimal magnitude, frequency, and duration. PMID: 20407890 ---------- [6] J Osteoporos. 2014;2014:702589. doi: 10.1155/2014/702589. Epub 2014 Jun 18. Effects of whole body vibration and resistance training on bone mineral density and anthropometry in obese postmenopausal women. Zaki ME(1). Free full text: http://www.hindawi.com/journals/jos/2014/702589/ Objective. The aim of this study was to evaluate the impact of two exercise programs, whole body vibration and resistance training on bone mineral density (BMD) and anthropometry in obese postmenopausal women. Material and Methods. Eighty Egyptian obese postmenopausal women were enrolled in this study; their age ranged from 50 to 68 years. Their body mass index ranged (30-36 kg/m(2)). The exercise prescription consisted of whole body vibration (WBV) and resistance training. Bone mineral density (BMD) and anthropometrical parameters were measured at the beginning and at the end of the study. Changes from baseline to eight months in BMD and anthropometric parameters were investigated. Results. BMD at the greater trochanter, at ward's triangle, and at lumbar spine were significantly higher after physical training, using both WBV and resistive training. Moreover, both exercise programs were effective in BMI and waist to the hip ratio. Simple and multiple regression analyses showed significant associations between physical activity duration and BMD at all sites. The highest values of R (2) were found for the models incorporating WBV plus BMI. Conclusion. The study suggests that both types of exercise modalities had a similar positive effect on BMD at all sites in obese postmenopausal women. Significant association was noted between physical activity and anthropometric variables and BMD measures at all sites. PMCID: PMC4086652 PMID: 25136473 ------------ [7] J Bone Miner Res. 2015 Jul;30(7):1319-28. doi: 10.1002/jbmr.2448. Low-Magnitude Mechanical Stimulation to Improve Bone Density in Persons of Advanced Age: A Randomized, Placebo-Controlled Trial. Kiel DP(1,)(2,)(3), Hannan MT(1,)(2,)(3), Barton BA(4), Bouxsein ML(3,)(5), Sisson E(6), Lang T(7), Allaire B(5), Dewkett D(1), Carroll D(1), Magaziner J(8), Shane E(9), Leary ET(10,)(11), Zimmerman S(12), Rubin CT(13). Nonpharmacologic approaches to preserve or increase bone mineral density (BMD) include whole-body vibration (WBV), but its efficacy in elderly persons is not clear. Therefore, we conducted the Vibration to Improve Bone in Elderly Subjects (VIBES) trial, a randomized, placebo-controlled trial of 10 minutes of daily WBV (0.3g at 37 Hz) in seniors recruited from 16 independent living communities. The primary outcomes were volumetric BMD of the hip and spine measured by quantitative computed tomography (QCT) and biochemical markers of bone turnover. We randomized 174 men and women (89 active, 85 placebo) with T-scores -1 to -2.5 who were not taking bone active drugs and had no diseases affecting the skeleton (mean age 82 ± 7 years, range 65 to 102). Participants received daily calcium (1000 mg) and vitamin D (800 IU). Study platforms were activated using radio frequency ID cards providing electronic adherence monitoring; placebo platforms resembled the active platforms. In total, 61% of participants in the active arm and 73% in the placebo arm completed 24 months. The primary outcomes, median percent changes (interquartile range [iQR]) in total volumetric femoral trabecular BMD (active group (2.2% [-0.8%, 5.2%]) versus placebo 0.4% [-4.8%, 5.0%]) and in mid-vertebral trabecular BMD of L1 and L2 (active group (5.3% [-6.9%, 13.3%]) versus placebo (2.4% [-4.4%, 11.1%]), did not differ between groups (all p values > 0.1). Changes in biochemical markers of bone turnover (P1NP and sCTX) also were not different between groups (p = 0.19 and p = 0.97, respectively). In conclusion, this placebo-controlled randomized trial of daily WBV in older adults did not demonstrate evidence of significant beneficial effects on volumetric BMD or bone biomarkers; however, the high variability in vBMD changes limited our power to detect small treatment effects. The beneficial effects of WBV observed in previous studies of younger women may not occur to the same extent in elderly individuals. © 2015 American Society for Bone and Mineral Research. PMCID: PMC4834704 [Available on 2016-07-01] PMID: 25581217
  2. Does anyone else eat natto, the fermented soybean product which is quite popular in Japan? It is the richest food source of vitamin K2 (menaquinone-7 or MK-7) with 1 mg (1000 mcg) of K2 per 100g natto. That is about 20x higher than the next highest source, certain cheeses like Gouda. Unlike vitamin K1 which is found primarily in leafy greens, there is virtually no vitamin K2 in regular fruits and vegetables. Why should we care about vitamin K2 you ask? First and foremost because it has been shown to be protective against osteoporosis [1-2], a concern for CR practitioners. From [2], a study of 244 postmenopausal women supplemented with 180mcg/day of Vitamin K2 (MK-7) for three years: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae. CONCLUSIONS: MK-7 supplements may help postmenopausal women to prevent bone loss. Another significant benefit of Vitamin K2 is for cardiovascular health. Vitamin K2 seems to prevent artery calcification (aka hardening of the arteries) [3-5], which happens when calcium circulating in the blood is turned into a crust in the arteries. In study [5] the same group of researchers from [2] measured arterial calcification in the same 244 postmenopausal women on 180mcg/day of K2 for three years, and found multiple markers of arterial stiffness improved with K2 supplementation, concluding: Long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. But those were studies of direct supplementation of vitamin K2 (MK-7), rather than getting it from food. Does eating natto actually raise serum MK-7 levels? Thankfully the answer is yes, according to [6]: erum MK-7 level with the frequency of dietary natto intake were examined in 134 healthy adults (85 men and 39 women) without and with occasional (a few times per month), and frequent (a few times per week) dietary intake of regular natto including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated osteocalcin concentrations in men with the occasional or frequent dietary intake of natto were significantly higher than those without any intake. So where to get natto? I buy my natto in frozen form at my local asian market, for about $2.50 for four styrofoam containers each of which contains about 50g of natto. Here is what the package of four look like: I eat half of a container's worth of natto per day (cost ~ $0.30/day). That 25g of natto per day provides about 250mcg of Vitamin K2 (MK-7), which is about 30% more than the dose shown to improve bone health [2] and reduce arterial stiffness [5] in postmenopausal women. What's natto like you ask? There is no getting around the fact that it looks pretty gross, and has a very slimy texture. As a result, many people can't stomach it, but I actually enjoy the taste, especially when mixed into the serving of other legumes and starches I eat. Below is a photo of natto in the styrofoam container. Pretty appetizing, huh?! The chopsticks in the photo are helpful for scale: For those of you who would be too grossed out by natto to eat it, there are supplements available. In fact I take one of these* to increase my K2 beyond what I get from natto - adding an extra 100mcg MK-7 per day for $0.09. But I'm always in favor of getting nutrients from food sources when practical. This is one of the rare cases where the natural food source is price competitive with supplement sources. So for me natto is a good choice. Does anyone else eat natto? If not, you might consider giving it a try! [Note: This post does not address Natto's brain health benefits. For discussion of that, see this post further down this thread.] --Dean *Note - I've updated my supplement regime to this vegan NOW Foods brand K2 supplement, to make sure I'm getting K2 in MK-7 form, rather than (mostly) MK-4 per my previous supplement. --------- [1] J Bone Miner Metab. 2014 Mar;32(2):142-50. doi: 10.1007/s00774-013-0472-7. Epub 2013 May 24. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. Koitaya N(1), Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y. Author information: (1)Department of Food Function and Labeling, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjyuku-ku, Tokyo, Japan. Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial. The participants (aged 50-65 years) were randomly assigned to one of two groups according to the MK-4 dose received: the placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups (>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were significantly lower in the MK-4 group than in the control group. In the control group, there was no significant change in serum pentosidine concentrations. However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months was significantly lower than that at baseline. The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6-12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects. PMID: 23702931 ------------ [2] Osteoporos Int. 2013 Sep;24(9):2499-507. doi: 10.1007/s00198-013-2325-6. Epub 2013 Mar 23. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Knapen MH(1), Drummen NE, Smit E, Vermeer C, Theuwissen E. Author information: (1)VitaK, Maastricht University, Oxfordlaan 70, 6229 EV, Maastricht, The Netherlands. We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss.INTRODUCTION: Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health. METHODS: Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment. RESULTS: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae. CONCLUSIONS: MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation. PMID: 23525894 ----------- [3] Acta Physiol Hung. 2010 Sep;97(3):256-66. doi: 10.1556/APhysiol.97.2010.3.2. Vitamin K and vascular calcifications. Fodor D(1), Albu A, Poantă L, Porojan M. Author information: (1)University of Medicine and Pharmacy, 2nd Internal Medicine, Clinic Iuliu Hatieganu, Cluj-Napoca, Romania. dfodor@umfcluj.ro The role of vitamin K in the synthesis of some coagulation factors is well known. The implication of vitamin K in vascular health was demonstrated in many surveys and studies conducted over the past years on the vitamin K-dependent proteins non-involved in coagulation processes. The vitamin K-dependent matrix Gla protein is a potent inhibitor of the arterial calcification, and may become a non-invasive biochemical marker for vascular calcification. Vitamin K(2) is considered to be more important for vascular system, if compared to vitamin K(1). This paper is reviewing the data from recent literature on the involvement of vitamin K and vitamin K-dependent proteins in cardiovascular health. PMID: 20843764 ---------------- [4] Nutrients. 2015 Aug 18;7(8):6991-7011. doi: 10.3390/nu7085318. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification. Scheiber D(1), Veulemans V(2), Horn P(3), Chatrou ML(4), Potthoff SA(5), Kelm M(6,)(7), Schurgers LJ(8), Westenfeld R(9). Author information: (1)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. daniel.scheiber@med.uni-duesseldorf.de. (2)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. verena.veulemanns@med.uni-duesseldorf.de. (3)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. patrick.horn@med.uni-duesseldorf.de. (4)Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht 6229 ER, The Netherlands. m.chatrou@maastrichtuniversity.nl. (5)Department of Nephrology, University Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany. sebastian.potthoff@med.uni-duesseldorf.de. (6)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. malte.kelm@med.uni-duesseldorf.de. (7)Cardiovascular Research Institute Duesseldorf, University Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany. malte.kelm@med.uni-duesseldorf.de. (8)Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht 6229 ER, The Netherlands. l.schurgers@maastrichtuniversity.nl. (9)Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. ralf.westenfeld@med.uni-duesseldorf.de. Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMCID: PMC4555157 PMID: 26295257 ------------- [5] Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb 19. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C(1). Author information: (1)Cees Vermeer, PhD, VitaK, Maastricht University, Biopartner Center Maastricht, Oxfordlaan 70, 6229 EV Maastricht, The Netherlands, Tel: +31 43 388 5865, Fax: +31 43 388 5889, E-mail: c.vermeer@vitak.com. Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index βsignificantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. PMID: 25694037 ---------- [6] J Bone Miner Metab. 2000;18(4):216-22. Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals. Tsukamoto Y(1), Ichise H, Kakuda H, Yamaguchi M. Author information: (1)Central Research Institute, Mitsukan Group Co., Ltd., Aichi, Japan. Changes in circulating vitamin K2 (menaquinone-7, MK-7) and gamma-carboxylated osteocalcin concentrations in normal individuals with the intake of fermented soybeans (natto) were investigated. Eight male volunteers were given sequentially fermented soybeans (natto) containing three different contents of MK-7 at an interval of 7 days as follows: regular natto including 775 micrograms/100 g (MK-7 x 1) or reinforced natto containing 1298 micrograms/100 g (MK-7 x 1.5) or 1765 micrograms/100 g (MK-7 x 2). Subsequently, it was found that serum MK-7 and gamma-carboxylated osteocalcin concentrations were significantly elevated following the start of dietary intake of MK-7 (1298 or 1765 micrograms/100 g). Serum undercarboxylated osteocalcin concentrations were significantly decreased by dietary MK-7 (1765 micrograms/100 g) supplementation. Moreover, the changes in serum MK-7 level with the frequency of dietary natto intake were examined in 134 healthy adults (85 men and 39 women) without and with occasional (a few times per month), and frequent (a few times per week) dietary intake of regular natto including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated osteocalcin concentrations in men with the occasional or frequent dietary intake of natto were significantly higher than those without any intake. The present study suggests that intake of fermented soybean (natto) increases serum levels of MK-7 and gamma-carboxylated osteocalcin in normal individuals. PMID: 10874601
  3. Saul

    CR and osteoporosis

    Dear ALL, I've just sent an email to Prof. James Whitfield, distinguished retired Prof. of the Canadian CRC in Ottawa -- Prof. Whitfield is one of the world's leading experts on osteoporosis: As you recommended in 2013, I switched from Forteo to Prolia; this showed an improvement in my last Dexa (a little under two years ago); however, according to the former head of Orthopedics here at UR, this improvement is illusory. After switching to Prolia, I noticed that my nails became much weaker: Posts in the Calorie Restriction Society Website suggest that this is normal for those practicing Calorie Restriction. However, I recall that nail strength correlates with bone density -- so to me this suggests the likelihood of worsened osteoporosis. Happily, my endocrinologist (Professor Steven Wittlin, Head of Endocrinology at UR Medicine) has put me back on Forteo (at my request). I've been on daily injections of Forteo for a little under two weeks -- almost immediately, my nails grew hard -- I haven't seen them like this for more years than I can remember. Also: My nails are growing faster. Previously, I didn't need to cut them more than once a month -- now, probably about every 2.5 weeks. This (almost immediate) change in nails -- harder nails, faster growing nails -- if it translates to bones -- suggests improved changes in bone density, and in growth of new bones -- in other words, Forteo having it's usual osteogenic effects. As usual, I'd very much appreciate your thoughts on that. Concerning my daughters: The oldest, Ashira, is halfway through the MD/PhD program at NYU; she is married, with a 5 month old son -- my first grandson! The youngest, Meira, finished her Bachelor's Degree at UNC Chapel Hill, major Economics, and is currently working for KPMG (a large international tax firm); she has a boyfriend who I fully approve of. Both daughters, my son-in-law and grandson came to stay with us for the first two days of Passover last weekend. (Both daughters live in Lower Manhattan.) -- Saul On 02/16/2013 02:27 PM, James Whitfield wrote: Hi Saul: It seems that for a period Forteo works but then the response slows down. This is known to happen. It might be wise to put pauses into the Forteo treatment. During a pause the bone would regain its osteogenic responsiveness to Forteo as you have in fact seen. During the pause you could try the RANKL blocker. In other words try a pulsed treatment. How are the girls? <Jim> -----Original Message----- From: Saul Lubkin [mailto:saul.lubkin@rochester.edu] Sent: February-16-13 12:44 PM To: James F. Whitfield Cc: Steven Wittlin Subject: Possibility and wisdom of taking Forteo and with Prolia Dear Prof. Whitfield, It's a pleasure to contact you again! I hope that life has been good to you, and that your new research interest in Alzheimer's disease has been progressing well. My personal reason for writing you concerns, as usual, osteoporosis, about which you of course continue to be one of the world's leading experts. Let me describe my current situation: I've been on Forteo for quite a while, and it's been improving my bone density at multiple sites. As I noted, in 2008, my Endocrinologist, Dr. Wittlin, noted little if any improvement on my dexa. So I was switched to a biphosphonate. After 6 months on the biphosphonate, my bone density plummeted. So, I went back to Forteo, and bone density began building up again, at a good pace. And I've been on Forteo up to and including the present. However, I've had a Dexa last Monday -- and it showed little change in the spine, a small loss of bonethe femoral necks (-6.4%) and a small gain in the trochanters (+1.9%). Dr. Wittlin thought it might be best to switch me to Prolia. My understanding is that Prolia binds to RANKL, which is expressed by osteoblasts, preventing RANKL from binding to RANK, expressed by pre-osteoclasts, and thus preventing the pre-osteoclasts from developing into osteoclasts, thus reducing the normal bone resorption accomplished by osteoclasts, and therefore helping -- not really to build new bone, but reduce the rate at which bone is resorbed. In this effect, it resembles the effect of biphosphonates; both also reduce the remodelling rate. Because of my bad experience with biphosphonates, I am very reluctant to try a drug that resembles the effect of biphosphonates -- although admittedly by a very different pathway. Continuing with Forteo, I think, is likely to at least maintain what gains I currently have achieved, and prevent rapid loss of bone density. The possibility has occurred to me of taking BOTH Forteo and Prolia. I recall that previous studies have shown that, taking both Forteo and biphosphonates is essentially equivalent to taking biphosphonates alone -- the effects of Forteo overwhelm those of the biphosphonates. This suggests to me (correctly or not?) that Forteo combined with Prolia would not slow the remodelling rate -- my guess is, that the enhanced remodelling induced by Forteo would persist. It's possible that the Prolia might be effective in reducing the rate of maturation of pre-osteoclasts, as it usually does; and that the combination might thus be effective in growing bone, in my type of osteoporotic: A slow remodeller. Your thoughts on this would be much appreciated -- and if you think that the combination might be worth a try, I'd like to try it, if possible. At any rate, it's a pleasure to contact you again; and let me again congratulate you on your being awarded the much justified title of "Emeritus Researcher for Life". -- Saul
  4. Hello! I am a woman of reproductive age and am interested in the idea of CR. I am looking for information on how this affects the hormonal profile and function, and whether it causes amenorrhea, and if so, whether this is by default a bad thing. Most of the information on amenorrhea I can find tends to refer to anorexic or overly athletic individuals and classifies this as a non-desirable or pathological occurrence. However, I have read before that having fewer periods and lower levels of female hormones can have a protective effect against cancers. If I go on a CR diet, will I be at risk of losing my periods, and is this dangerous to my health if so? What is the experience of other CR women, and have their been tests or studies on this particular topic? Any help pointing me in the direction of resources on this topic would be greatly appreciated. Thank you!
  5. All, In today's video (embedded below), Dr. Greger highlights an ex vivo study [1] of almond consumption and bone health, which I thought was pretty cool and promising, despite it being sponsored by the Almond Board of California. Ex vivo you say? I've heard of in vivo and in vitro, but what is ex vivo? It's when you treat a subject, in this case by feeding them a handful of almonds, wait a few hours, and then draw some of their blood in order to drip it on something outside the body (e.g. cancer cells) to see how the cells reacts (hence ex vivo - latin for "outside the living"). In this case they took the blood of almond-consuming subjects and dripped it on osteoclast cells, the cells in our bones whose job it is to break down bone cells, and whose activity is an important contributor to osteoporosis. They found osteoclast proliferation and activity was markedly reduced (a good thing) by the blood of the almond consumers relative to the blood of controls, suggesting almonds should have a positive effect on maintaining bone health by reducing bone tissue breakdown. This jibes with at least one population study [2], which found almonds to be one of foods associated with reduced osteoporosis. As we all know, the problems with population studies are many, including relying of dubious food frequency questionnaires, and being confounded by many lifestyle differences between the participants that could have been responsible for the observed effect (reduced osteoporosis), rather than the almonds. The sort of ex vivo experiment done in [1] gets the best of both worlds. It has the advantage of studying real people eating and importantly, digesting and assimilating known reasonable quantities of real whole foods, rather than just dripping purified almond extracts directly onto osteoclasts in a petri dish. But at the same time it allows researchers to look at the details of the mechanisms involved, without invasive procedures, which in this case would have entailed a dangerous and painful bone marrow biopsy, which no IRB would allow in a human study. Anyway, pretty cool, and seemingly reasonable evidence that almonds (and probably other nuts) may be beneficial for preventing bone loss. --Dean --------- [1] Metabolism. 2011 Jul;60(7):923-9. doi: 10.1016/j.metabol.2010.08.012. Epub 2010 Oct 13. Postprandial effects of almond consumption on human osteoclast precursors--an ex vivo study. Platt ID(1), Josse AR, Kendall CW, Jenkins DJ, El-Sohemy A. Author information: (1)Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Consumption of almonds has been associated with increased bone mineral density, but the direct effects of almonds on bone cells are not known. We determined whether serum obtained following the consumption of a meal containing 60 g of almonds affects human osteoclast formation, function, and gene expression in vitro. Human osteoclast precursors were cultured in medium containing 10% serum obtained from 14 healthy subjects at baseline and 4 hours following the consumption of 3 test meals containing almonds, potatoes, and rice and balanced for macronutrient composition. Osteoclast formation was determined by the number of tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells, and osteoclast function was assessed by measuring TRAP activity in the culture medium and calcium released from OsteoAssay (Lonza Walkersville, Walkersville, MD, USA) plates. The expression of cathepsin K, receptor activator of nuclear factor kB, and matrix metalloproteinase-9 genes was measured by real-time reverse transcriptase-polymerase chain reaction. Compared with serum obtained at baseline, serum obtained 4 hours following the consumption of the almond meal reduced osteoclast formation by approximately 20%, TRAP activity by approximately 15%, calcium release by approximately 65%, and the expression of cathepsin K, receptor activator of nuclear factor kB, and matrix metalloproteinase-9 by 13% to 23%. No effects were observed with serum obtained from the other test meals. Serum obtained 4 hours following the consumption of an almond meal inhibits osteoclast formation, function, and gene expression in cultured human osteoclast precursors, and provides evidence for a positive effect of almonds on bone health. Copyright © 2011 Elsevier Inc. All rights reserved. PMID: 20947104 ------------- [2] BMC Musculoskelet Disord. 2008 Feb 27;9:28. doi: 10.1186/1471-2474-9-28. The assessment of osteoporosis risk factors in Iranian women compared with Indian women. Keramat A(1), Patwardhan B, Larijani B, Chopra A, Mithal A, Chakravarty D, Adibi H, Khosravi A. Author information: (1)Shahroud University of Medical Sciences, Hafte Tir Avenue, Shahroud, Iran. keramat1@yahoo.com BACKGROUND: Osteoporosis is an important public health problem in older adults. It is more common in postmenopausal women and not only gives rise to morbidity but also markedly diminishes the quality of life in this population. There is lack of information about the risk factor of osteoporosis in developing countries. In this study we aimed to assess the risk factors for osteoporosis in postmenopausal women from selected BMD centers of two developing Asian countries (Iran and India). METHODS: This study is a multicenter interview-based study conducted in selected hospitals and health centers from urban areas in Iran and India. The case group included postmenopausal osteoporotic women who were identified as patients with bone density higher than 2.5 SD below average of young normal bone density (in L1-L4) spine region interest and/or total femoral region) by using DEXA method. The controls were chosen from postmenopausal women with normal bone density (in L1-L4 spine and total femoral regions using DEXA method) matching in age groups was strategy of choice.The sample sizes included from Iran a total of 363 subjects (178 osteoporotic and 185 normal) and from India a total of 354 subjects (203 osteoporotic and 151 normal). RESULTS: The significant (p < 0.05) risk factors in present study population with their Odds Ratios (in parenthesis, respectively in Iran and India) were as follow:Lower education defined as less than class 12 or nil college (2.1) (2.7), duration of menopause greater than 5 years: (2.2) (1.4), Menarche age (after 14 years): (1.9) (1.6), Menopause age (before 45 years): (1.1) (2), Parity more than 3: (1.1) (1), Bone and joint problem (2.3) (2.2). Calcium supplementation (0.6) and HRT (0.4) were shown as protective factors and steroid therapy (3.3) was found as a risk factor in Iran. Calcium supplementation more than 1 year (0.3) was shown as a protective factor in India.Pure vegetarianism: (2.2) and Red meat consumption more than 4 times per week (1.4) was shown as a risk factor in Indian and Iranian subjects respectively. Regular consumption of Soya (0.3), almond (0.5), fish (0.5), fruits (0.4) and milk tea 4 cups per day and more (0.4) appeared to be significant protective factors in India. Regular consumption of cheese (0.5), milk (0.5), chicken (0.4), egg (0.6), fruit (0.4), tea 7 cups per day and more (0.3) were found to be significant protective factors in Iran. Exercises were shown as protective factor in Iran (0.4) and India (0.4). There were no significant differences in association of risk factors and osteoporosis between Iranian and Indian subjects. CONCLUSION: Osteoporosis in Iranian and Indian subjects also appears to be associated with several known risk factors that well described in the literature. There were no significant differences in association of risk factors and osteoporosis between Iranian and Indian subjects. It was shown a protective role of certain nutritional dietary components and also exercises in both populations and can be exploited in preventive educational strategies on osteoporosis in these populations. PMCID: PMC2289820 PMID: 18304358
  6. All, Al posted a new review article [1] which discusses all the available evidence relating calorie restriction, protein restriction, and methionine restriction to bone health. It basically goes over many of the things we've discussed here before - like the fact that DEXA bone scanners aren't well-calibrated for very thin people, and that CRed organisms have lighter bones, but not necessarily bones that are lower in quality, or more fragile. I like the way they summarize in the free full text: In the pursuit of survival with enhanced growth and development, human beings have come to suffer the negative effects of excessive nutrition.Currently, it may be appropriate to reevaluate the possibility that dietary restriction actually shapes a skeletal system to a size or mass suitable for the organism rather than causes an unfavorable loss of bone mineral. A philosophy of achieving optimal bone quality may be more important than preserving maximal bone size/mass when considering skeletal health under various dietary restrictions. As I said, nothing really new, but it's nice to see all the reassuring evidence suggesting our skeletons aren't crumbling away as a result of CR. --Dean ------------ [1] Ann N Y Acad Sci. 2016 Feb 16. doi: 10.1111/nyas.13004. [Epub ahead of print] Dietary restrictions, bone density, and bone quality. Huang TH(1), Ables GP(2). Author information: (1)Laboratory of Exercise, Nutrition and Bone Biology, Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Tainan, Taiwan. (2)Orentreich Foundation for the Advancement of Science, Cold Spring-on-Hudson, New York. Free full text: http://onlinelibrary.wiley.com/doi/10.1111/nyas.13004/epdf Caloric restriction (CR), protein restriction (PR), and specific amino acid restriction (e.g., methionine restriction (MR)) are different dietary interventions that have been confirmed with regard to their comprehensive benefits to metabolism and health. Based on bone densitometric measurements, weight loss induced by dietary restriction is known to be accompanied by reduced areal bone mineral density, bone mass, and/or bone size, and it is considered harmful to bone health. However, because of technological advancements in bone densitometric instruments (e.g., high-resolution X-ray tomography), dietary restrictions have been found to cause a reduction in bone mass/size rather than volumetric bone mineral density. Furthermore, when considering bone quality, bone health consists of diverse indices that cannot be fully represented by densitometric measurements alone. Indeed, there is evidence that moderate dietary restrictions do not impair intrinsic bone material properties, despite the reduction in whole-bone strength because of a smaller bone size. In the present review, we integrate research evidence from traditional densitometric measurements, metabolic status assays (e.g., energy metabolism, oxidative stresses, and inflammatory responses), and biomaterial analyses to provide revised conclusions regarding the effects of CR, PR, and MR on the skeleton. © 2016 New York Academy of Sciences. PMID: 26881697
  7. Dean Pomerleau

    Tea & Bone Health

    Tea Reduces Fracture Risk All, A new prospective study [1] reported on here found that elderly women who drank the most tea had a 30% reduced risk of osteoporotic fractures compared with women who abstained from drinking tea. In the study, researchers followed ~1200 women age 75+ for 10 years and associated their tea drinking habits with subsequence risk of fracture. Here is the highlight from the abstract: In comparison with the lowest tea intake category (≤1 cup/wk), consumption of ≥3 cups/d was associated with a 30% decrease in the risk of any osteoporotic fracture (HR: 0.70; 95% CI: 0.50, 0.96). Compared with women in the lowest tertile of total flavonoid intake (from tea and diet), women in the highest tertile had a lower risk of any osteoporotic fracture (HR: 0.65; 95% CI: 0.47, 0.88), major osteoporotic fracture (HR: 0.66; 95% CI: 0.45, 0.95), and hip fracture (HR: 0.58; 95% CI: 0.36, 0.95). No mention is made of a comparison between the relative effects of black vs. green tea on fracture risk in this cohort. Given the subjects were Australian women, it is likely they were drinking mostly black tea so no meaningful comparison could be made. I recently started drinking a combination of black and green tea based on suggestive evidence that black tea may have some health benefits that green tea does not, and visa versa. This study could be interested as further (albeit weak) support such a strategy. --Dean P.S. Here is a nice infographic on the health benefits of Coffee vs. Tea, although bone health isn't mentioned as a benefit for either one. --------------- [1] Am J Clin Nutr. 2015 Oct;102(4):958-65. doi: 10.3945/ajcn.115.109892. Epub 2015 Aug 12. Tea and flavonoid intake predict osteoporotic fracture risk in elderly Australian women: a prospective study. Myers G(1), Prince RL(2), Kerr DA(3), Devine A(4), Woodman RJ(5), Lewis JR(2), Hodgson JM(6). BACKGROUND: Observational studies have linked tea drinking, a major source of dietary flavonoids, with higher bone density. However, there is a paucity of prospective studies examining the association of tea drinking and flavonoid intake with fracture risk. OBJECTIVE: The objective of this study was to examine the associations of black tea drinking and flavonoid intake with fracture risk in a prospective cohort of women aged >75 y. DESIGN: A total of 1188 women were assessed for habitual dietary intake with a food-frequency and beverage questionnaire. Incidence of osteoporotic fracture requiring hospitalization was determined through the Western Australian Hospital Morbidity Data system. Multivariable adjusted Cox regression was used to examine the HRs for incident fracture. RESULTS: Over 10 y of follow-up, osteoporotic fractures were identified in 288 (24.2%) women; 212 (17.8%) were identified as a major osteoporotic fracture, and of these, 129 (10.9%) were a hip fracture. In comparison with the lowest tea intake category (≤1 cup/wk), consumption of ≥3 cups/d was associated with a 30% decrease in the risk of any osteoporotic fracture (HR: 0.70; 95% CI: 0.50, 0.96). Compared with women in the lowest tertile of total flavonoid intake (from tea and diet), women in the highest tertile had a lower risk of any osteoporotic fracture (HR: 0.65; 95% CI: 0.47, 0.88), major osteoporotic fracture (HR: 0.66; 95% CI: 0.45, 0.95), and hip fracture (HR: 0.58; 95% CI: 0.36, 0.95). For specific classes of flavonoids, statistically significant reductions in fracture risk were observed for higher intake of flavonols for any osteoporotic fracture and major osteoporotic fracture, as well as flavones for hip fracture (P < 0.05). CONCLUSION: Higher intake of black tea and particular classes of flavonoids were associated with lower risk of fracture-related hospitalizations in elderly women at high risk of fracture. PMID: 26269364
  8. Here is another gem of a study [1] from James Cain latest weekly CR research update (thanks James!) worth its own thread. In this study, the researchers subjected mice to pretty severe (40%) CR either starting very young (4 weeks) or starting late in life (48 or 68 weeks). CR started in the oldest mice (68 weeks) and lasting for 12 weeks had negative effects on their bone health. When CR was started young (4 weeks), there was an initial period when the bone health of the CR'ed mice was profoundly compromised, both in terms of bone mineral density and force required to break the femur. But over the lifetime of the early-onset CR'ed mice, their bone health improved markedly, both in terms bone mineral density and the microarchitecture of the bone. In short, the bones of mice who started CR at a young age were light but strong when they got old. That is comforting, and accords with the finding [2] from Luigi Fontana on some of us human calorie restrictors that our bones are healthy despite long-term CR. --Dean --------- [1] J Bone Miner Res. 2015 Nov 17. doi: 10.1002/jbmr.2745. [Epub ahead of print] Dietary Restriction-Induced Alterations in Bone Phenotype: Effects of Lifelong Versus Short-Term Caloric Restriction on Femoral and Vertebral Bone in C57BL/6 Mice. Behrendt AK(1,)(2), Kuhla A(2), Osterberg A(3), Polley C(2), Herlyn P(1), Fischer DC(4), Scotland M(1), Wree A(5), Histing T(6), Menger MD(7), Müller-Hilke B(3), Mittlmeier T(1), Vollmar B(2). Caloric restriction (CR) is a well-described dietary intervention that delays the onset of aging-associated biochemical and physiological changes thereby extending the lifespan of rodents. The influence of CR on metabolism, strength and morphology of bone has been controversially discussed in literature. Thus, the present study evaluated whether lifelong CR versus short-term late-onset dietary intervention differentially affects the development of senile osteoporosis in C57BL/6 mice. Two different dietary regimens with 40% food restriction were performed: lifelong CR starting in 4wk-old mice was maintained for 4, 20 or 74 weeks. In contrast, short-term late-onset CR lasting a period of 12 weeks was commenced at 48 or 68 weeks of age. Control mice were fed ad libitum (AL). Bone specimens were assessed using microcomputed tomography (µCT, femur and lumbar vertebral body) and biomechanical testing (femur). Adverse effects of CR, including reduced cortical bone mineral density (Ct.BMD) and thickness (Ct.Th) were detected to some extent in senile mice (68 + 12w) but in particular in cortical bone of young growing mice (4 + 4w), associated with reduced femoral failure force (F). However, we observed a profound capacity of bone to compensate these deleterious changes of minor nutrition with increasing age presumably via reorganization of trabecular bone. Especially in lumbar vertebrae, lifelong CR lasting 20 or 74 weeks had beneficial effects on trabecular bone mineral density (Tb.BMD), bone volume fraction (BV/TV) and trabecular number (Tb.N). In parallel, lifelong CR groups showed reduced structure model index values compared to age-matched controls indicating a transformation of vertebral trabecular bone microarchitecture towards a plate-like geometry. This effect was not visible in senile mice after short-term 12-week CR. In summary, CR has differential effects on cortical and trabecular bone dependent on bone localization and starting age. Our study underlines that bone compartments possess a lifelong capability to cope with changing nutritional influences. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. PMID: 26572927 ------------------- [3] Aging Cell. 2011 Feb;10(1):96-102. doi: 10.1111/j.1474-9726.2010.00643.x. Epub 2010 Nov 15. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition. Villareal DT(1), Kotyk JJ, Armamento-Villareal RC, Kenguva V, Seaman P, Shahar A, Wald MJ, Kleerekoper M, Fontana L. Author information: (1)Division of Geriatrics and Nutritional Science, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. Calorie restriction (CR) reduces bone quantity but not bone quality in rodents. Nothing is known regarding the long-term effects of CR with adequate intake of vitamin and minerals on bone quantity and quality in middle-aged lean individuals. In this study, we evaluated body composition, bone mineral density (BMD), and serum markers of bone turnover and inflammation in 32 volunteers who had been eating a CR diet (approximately 35% less calories than controls) for an average of 6.8 ± 5.2 years (mean age 52.7 ± 10.3 years) and 32 age- and sex-matched sedentary controls eating Western diets (WD). In a subgroup of 10 CR and 10 WD volunteers, we also measured trabecular bone (TB) microarchitecture of the distal radius using high-resolution magnetic resonance imaging. We found that the CR volunteers had significantly lower body mass index than the WD volunteers (18.9 ± 1.2 vs. 26.5 ± 2.2 kg m(-2) ; P = 0.0001). BMD of the lumbar spine (0.870 ± 0.11 vs. 1.138 ± 0.12 g cm(-2) , P = 0.0001) and hip (0.806 ± 0.12 vs. 1.047 ± 0.12 g cm(-2) , P = 0.0001) was also lower in the CR than in the WD group. Serum C-terminal telopeptide and bone-specific alkaline phosphatase concentration were similar between groups, while serum C-reactive protein (0.19 ± 0.26 vs. 1.46 ± 1.56 mg L(-1) , P = 0.0001) was lower in the CR group. Trabecular bone microarchitecture parameters such as the erosion index (0.916 ± 0.087 vs. 0.877 ± 0.088; P = 0.739) and surface-to-curve ratio (10.3 ± 1.4 vs. 12.1 ± 2.1, P = 0.440) were not significantly different between groups. These findings suggest that markedly reduced BMD is not associated with significantly reduced bone quality in middle-aged men and women practicing long-term calorie restriction with adequate nutrition. PMCID: PMC3607368 PMID: 20969721
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