第7回高槻・島本嚥下栄養研究会

4月13日（土）に第7回高槻・島本嚥下栄養研究会で「サルコペニアの嚥下障害とリハビリテーション栄養」の講演をします。詳細と申し込み用紙は下記HPを参照していただければと思います。お近くの方はよかったら御参加下さい。よろしくお願い申し上げます。

http://osaka.jdha.or.jp/pdf/info203.pdf

がんの筋肉量減少と筋肉の質低下は予後不良

肥満時代のがん悪液質：がん患者の筋肉量減少はBMIと独立した強力な予後予測因子であるという論文を紹介します。

Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, Murphy R, Ghosh S, Sawyer MB, Baracos VE. Cancer Cachexia in the Age of Obesity: Skeletal Muscle Depletion Is a Powerful Prognostic Factor, Independent of Body Mass Index. J Clin Oncol. 2013 Mar 25. [Epub ahead of print]

対象はがん患者（肺がんもしくは消化器がん）1473人です。筋肉量はCTでL3レベルの筋面積（腹筋、大腰筋、傍脊柱筋）を身長で2回割った骨格筋指数SMIで評価しています。同時に筋肉減衰muscle attenuation（筋肉内に脂肪が多いとCTで薄い）も評価しています。

結果ですが、生存期間に独立して関連があったのは、高度の体重減少、骨格筋指数低値、筋肉減衰低値（筋肉内に脂肪が多い）の3項目でした。3項目とも該当すると生存期間は8.4カ月でまったく該当しないと生存期間は28.4ヶ月でした。

以上より、CTによる筋肉量と筋肉の質（muscle quality）の評価は有用であり、現体重が肥満かるいそうかに関わらず、高度の体重減少、骨格筋指数低値、筋肉減衰低値で生存期間を予測できるという結論です。

図のように同じ骨格筋指数でもBMIが15.3と40.2の方がいたり、同じBMIでも骨格筋指数が33.7から58.3の方がいたり、同じBMIや骨格筋指数でも筋肉減衰が大きく異なったりしますので、身体計測だけでなく、画像による筋肉量と筋肉の質の評価は有用と言えます。

Abstract

PURPOSE
Emerging evidence suggests muscle depletion predicts survival of patients with cancer.
PATIENTS AND METHODS
At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models.
Results
Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P < .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P < .001).
CONCLUSION
CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.

悪液質のLカルニチンレビュー

悪液質に対するLカルニチンのレビュー論文を紹介します。

Robert Ringseis, Janine Keller, Klaus Eder. Mechanisms underlying the anti-wasting effect of l-carnitine supplementation under pathologic conditions: evidence from experimental and clinical studies. European Journal of Nutrition, DOI10.1007/s00394-013-0511-0

Lカルニチンの投与による窒素バランスの改善（蛋白合成増加もそくは蛋白分解減少）、アポトーシスの阻害、悪液質下での炎症反応の改善は、動物実験、ヒトでの臨床試験ともエビデンスがあります。酸化ストレスの緩和やミトコンドリア機能の改善は動物実験でのみ認めています。

Lカルニチン投与が悪液質に有効かどうかは、より大規模なRCTで検証されることが必要です。現時点では悪液質に対して試しに投与してもよいというところでしょうか。もちろん栄養療法や運動療法を併用した包括的対応の一環としてということになりますが。

Abstract

Purpose

Loss of skeletal muscle mass, also known as muscle wasting or muscle atrophy, is a common symptom of several chronic diseases, such as cancer and infectious diseases. Due to the strong negative impact of muscle loss on patient’s prognosis and quality of life, the development of efficacious treatment approaches to combat muscle wasting are of great importance. In order to evaluate the suitability of l-carnitine (LC) as an anti-wasting agent for clinical purposes the present review comprehensively summarizes the results from animal and clinical studies showing the effects of supplementation with LC or LC derivatives (acetyl-LC, propionyl-LC) on critical mechanisms involved in skeletal muscle loss under pathologic conditions, such as increased proteolysis, impaired protein synthesis, myonuclear apoptosis, inflammation, oxidative stress, and mitochondrial dysfunction.

Results

Evidence from both animal and clinical studies exists that LC supplementation causes an improved nitrogen balance either due to increased protein synthesis or reduced protein degradation, an inhibition of apoptosis and an abrogation of inflammatory processes under pathologic conditions. Furthermore, strong evidence has been provided, at least from animal studies, that LC supplementation prevents oxidative stress and ameliorates mitochondrial function, whereas results from a very low number of available clinical studies in this regard are inconclusive.

Conclusion

In conclusion, LC supplementation beneficially influences several critical mechanisms involved in pathologic skeletal muscle loss that may at least partially explain the anti-catabolic effects and the improvement of fatigue-related parameters following LC supplementation in patients with chronic diseases. However, more suitable clinical trials (double-blinded, randomized, placebo-controlled, large-scale) are necessary in order to establish LC supplementation as strategy for anti-wasting therapy.

サルコペニアと骨量減少、骨粗鬆症

日本女性のサルコペニアの有病割合と骨量減少、骨粗鬆症との関連をみた論文を紹介します。

Miyakoshi N, Hongo M, Mizutani Y, Shimada Y. Prevalence of sarcopenia in Japanese women with osteopenia and osteoporosis. J Bone Miner Metab. 2013 Mar 21. [Epub ahead of print]

対象は40-88歳の日本の女性2400人で、DEXAでサルコペニア、骨量減少osteopenia、骨粗鬆症osteoporosisを評価しています。若年の2標準偏差以下の筋肉量だった場合をサルコペニアとしています。

結果ですが、筋肉量と腰椎と大腿骨頸部の骨量に有意な相関を認めました（相関係数はそれぞれ0.197と0.274なので弱い相関です）。腰椎と大腿骨頸部の骨量は年齢と有意な負の相関を認めましたが、筋肉量は有意な相関を認めませんでした。

腰椎の骨量で評価した場合のサルコペニアの有病割合は、正常10.4％、骨量減少16.8％、骨粗鬆症20.4％でした。大腿骨頸部の骨量で評価した場合のサルコペニアの有病割合は、正常9.0％、骨量減少17.8％、骨粗鬆症29.7％でした。

サルコペニアと骨量減少、骨粗鬆症には独立した有意な関連を認めました。以上より、日本女性ではサルコペニアは骨量減少、骨粗鬆症と関連するという結論です。

サルコペニアと骨量減少、骨粗鬆症に関しては有意な関連を認めるという報告が多く、日本女性でも当てはまりそうです。年齢と筋肉量に有意な相関を認めなかったというのは気になりますが…。

Abstract

Sarcopenia and osteoporosis are both significant health burdens among postmenopausal women. This study examined associations between sarcopenia and osteopenia/osteoporosis in Japanese women and evaluated the prevalence of sarcopenia in women with osteopenia and osteoporosis. A total of 2400 Japanese women aged 40-88 years underwent dual-energy x-ray absorptiometry (DXA) scans of the whole body, lumbar spine, and total hip. Osteopenia and osteoporosis were defined according to World Health Organization criteria using bone mineral density (BMD) of the lumbar spine or hip. Sarcopenia was defined as a relative skeletal muscle index (RSMI) more than 2 standard deviations below the mean for a young adult reference population, calculated as the appendicular skeletal muscle mass (ASM) obtained from whole-body DXA divided by height in meters squared (RSMI = ASM/height²). Significant and marginal/moderate positive correlations were observed between RSMI and lumbar spine/total hip BMDs (r = 0.197 and r = 0.274, respectively; p < 0.0001 each). The BMDs of the lumbar spine and total hip showed significant moderate negative correlations with age (r = -0.270 and r = -0.375, respectively; p < 0.0001 each), but RSMI showed no association with age in this population (r = 0.056). When osteopenia/osteoporosis was defined using lumbar spine BMD, prevalences of sarcopenia in subjects with normal BMD, osteopenia and osteoporosis were 10.4, 16.8, and 20.4 %, respectively. When osteopenia/osteoporosis was defined using total hip BMD, the prevalences of sarcopenia in these subjects were 9.0, 17.8, and 29.7 %, respectively. A Chi-square test for independence showed a significant association between sarcopenia and osteopenia/osteoporosis (p < 0.0001). These results indicate that sarcopenia is significantly associated with osteopenia and osteoporosis in Japanese women.

シニアライフに関するNewsLetter

シニアライフに関するNewsLetterのNo3で、「リハビリテーション栄養から見たサルコペニア対策」の記事を掲載していただきました。サルコペニアの予防、診断、治療、リハ栄養、サルコペニアの嚥下障害について紹介しています。

下記HPでPDFで見れます。多くの方に見ていただけると嬉しいです。よろしくお願い申し上げます。

 http://www.nisshin-oillio.com/goods/support/pdf/letter_3.pdf

がん悪液質に対するenobosarm

選択的アンドロゲン受容体モジュレーターenobosarmのがん悪液質と身体機能に対する効果をみたフェーズ2のRCTを紹介します。

Adrian S Dobs, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. The Lancet Oncology, http://dx.doi.org/10.1016/S1470-2045(13)70055-X

リサーチクエスチョンは以下の通りです。

P：肥満がなく過去6ヶ月間に2％以上の体重減少をみとめたがん患者に
I：enobosarm（1mg、3mg）を113日間投与すると
C：プラセボと比較して
O：除脂肪体重（DEXAで測定）が増加する
D：RCT

結果ですが、プラセボ群では中央値0·02 kgの変化でしたが、1mg投与群では中央値1·5 kg, 幅−2·1 to 12·6、3mgでは中央値1·0 kg,幅 −4·8 to 11·5と前後比較で有意に除脂肪体重が増加しました。プラセボとの比較では1mg群がp=0.066、3mg群がp=0.041でした。

主な有害事象はがんの進行、肺炎、発熱性好中球減少症でしたが、プラセボ群とenobosarm（1mg、3mg）で著明な差はなく、enobosarmによるものではないと思われました。以上よりがん悪液質に対してenobosarmは除脂肪体重を増加させる可能性があるという結論です。

今回の研究では除脂肪体重が一次アウトカムでしたが、今後は身体機能・ADL・QOL・生存期間を一次アウトカムとした研究も行われるとよいですね。選択的アンドロゲン受容体モジュレーターenobosarmのフェーズ3の臨床研究も行われているようですので、その結果にも期待したいところです。

Summary

Background

Cancer-induced muscle wasting begins early in the course of a patient's malignant disease, resulting in declining physical function and other detrimental clinical consequences. This randomised, double-blind, placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm, a selective androgen receptor modulator, in patients with cancer.

Methods

We enrolled male (>45 years) and female (postmenopausal) patients with cancer who were not obese and who had at least 2% weight loss in the previous 6 months. Participants were randomly assigned (1:1:1 ratio, by computer generated list, block size three, stratified by cancer type) to receive once-daily oral enobosarm 1 mg, 3 mg, or placebo for up to 113 days at US and Argentinian oncology clinics. The sponsor, study personnel, and participants were masked to assignment. The primary endpoint was change in total lean body mass from baseline, assessed by dual-energy x-ray absorptiometry. Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol-specified window of within 10 days before baseline or first study drug, and within 10 days of day 113 or end of study (evaluable efficacy population). Adverse events and other safety measurements were assessed in the intention-to-treat (safety) population. This trial is registered with ClinicalTrials.gov, number NCT00467844.

Findings

Enrolment started on July 3, 2007, and the last patient completed the trial on Aug 1, 2008. 159 patients were analysed for safety (placebo, n=52; enobosarm 1 mg, n=53; enobosarm 3 mg, n=54). The evaluable efficacy population included 100 participants (placebo, n=34; enobosarm 1 mg, n=32; enobosarm 3 mg, n=34). Compared with baseline, significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups (enobosarm 1 mg median 1·5 kg, range −2·1 to 12·6, p=0·0012; enodosarm 3 mg 1·0 kg, −4·8 to 11·5, p=0·046). Change in total lean body mass within the placebo group (median 0·02 kg, range −5·8 to 6·7) was not significant (p=0·88). The most common serious adverse events were malignant neoplasm progression (eight of 52 [15%] with placebo vs five of 53 [9%] with enobosarm 1 mg vs seven of 54 [13%] with enobosarm 3 mg), pneumonia (two [4%] vs two [4%] vs three [6%]), and febrile neutropenia (three [6% vs one [2%] vs none). None of these events were deemed related to study drug.

Interpretation

Cancer cachexia is an unmet medical need and our data suggest that use of enobosarm might lead to improvements in lean body mass, without the toxic effects associated with androgens and progestational agents.

嚥下障害の早期発見とEAT-10

EAT-10日本語版は以下のHPからダウンロード可能です。
www.maff.go.jp/j/shokusan/seizo/kaigo/pdf/eat-10.pdf

嚥下障害患者の早期発見におけるEAT-10と多職種チームの役割に関するレビュー論文（書籍の章）を紹介します。

Kaspar K, Ekberg O. Identifying vulnerable patients: role of the EAT-10 and the multidisciplinary team for early intervention and comprehensive dysphagia care. Nestle Nutr Inst Workshop Ser. 2012;72:19-31. doi: 10.1159/000339977.

ヨーロッパでの話ですので、そのまま日本にあてはまるかどうかはわかりませんが、嚥下障害（特に軽度の）が見過ごされていて適切な対応を受けていないことが少なくありません。EAT-10を含めた妥当性のある嚥下スクリーニングを用いることは有用と思われます。

実際、系統的な嚥下スクリーニングプログラムによって、肺炎発症が55%減少し、入院期間が短縮したという報告があります。

日本では中等度～重度の嚥下障害患者（特に脳卒中）に対する嚥下リハが進んでいます。一方、加齢による軽度の嚥下機能低下（presbyphagia、老嚥）やサルコペニアの嚥下障害の評価と対応はまだ不十分です。日本でのEAT-10の有効性検証が必要です。

Abstract

There is underdiagnosis and low awareness of dysphagia despite that the condition is modifiable and poorly managed symptoms diminish psychological well-being and overall quality of life. Frontline clinicians are in a unique position to be alert to the high prevalence of swallowing difficulty among elderly, evaluate and identify those who need intervention, and assure that individuals receive appropriate care. Proper diagnosis and treatment of oral-pharyngeal dysphagia involves a multidisciplinary healthcare team effort and starts with systematic screening of at-risk patients. The presence of a medical condition such as acute stroke, head and neck cancer, head trauma, Alzheimer's disease, Parkinson's disease, pneumonia or bronchitis is adequate basis for predicting high risk. Systematic screening of dysphagia and resulting malnutrition among at-risk older adults is justified in an effort to avoid pneumonia and is recommended by clinical practice guidelines. Systematic screening with a validated method (e.g. the 10-item Eating Assessment Tool, EAT-10) as part of a comprehensive care protocol enables multidisciplinary teams to more effectively manage the condition, reduce the economic and societal burden, and improve patient quality of life. In fact, care settings with a systematic dysphagia screening program attain significantly better patient outcomes including reduced cases of pneumonia (by 55%) and reduced hospital length of stay.

外科患者の肥満パラドックス

外科患者の肥満パラドックスに関するレビュー論文を紹介します。

Tabita M. Valentijn , Wael Galal , Elke K.M. Tjeertes , Sanne E. Hoeks , Hence J. Verhagen , Robert Jan Stolker. The obesity paradox in the surgical population. The Surgeon, doi:10.1016/j.surge.2013.02.003

肥満バラドックスは心臓外科患者と非心臓外科患者に認めました。低栄養（るいそう）と病的肥満（BMI40以上）の患者は、術後も長期フォローアップ後も最も予後が悪かったです。

肥満バラドックスの原因として、除脂肪体重増加、（保護作用のある）末梢脂肪、炎症減少、遺伝、心血管疾患リスク因子の減少が考えられますが、おそらく未知の要因も関与していると思われます。

肥満パラドックスといっても、病的肥満では予後が悪く、太っていれば太っているほどよいという結果ではなかったので、慢性呼吸不全や慢性心不全などによる肥満パラドックスとは少し異なる印象です。肥満パラドックスという言葉を同じように使うべきか微妙な気もします。

Abstract

Background

Despite the medical hazards of obesity, recent reports examining body mass index (BMI) show an inverse relationship with morbidity and mortality in the surgical patient. This phenomenon is known as the ‘obesity paradox’. The aim of this review is to summarize both the literature concerned with the obesity paradox in the surgical setting, as well as the theories explaining its causation.

Methods

PubMed was searched to identify available literature. Search criteria included obesity paradox and BMI paradox, and studies in which BMI was used as a measure of body fat were potentially eligible for inclusion in this review.

Results

The obesity paradox has been demonstrated in cardiac and in non-cardiac surgery patients. Underweight and morbidly obese patients displayed the worse outcomes, both postoperatively as well as at long-term follow-up. Hypotheses to explain the obesity paradox include increased lean body mass, (protective) peripheral body fat, reduced inflammatory response, genetics and a decline in cardiovascular disease risk factors, but probably unknown factors contribute too.

Conclusions

Patients at the extremes of BMI, both the underweight and the morbid obese, seem to have the highest postoperative morbidity and mortality hazard, which even persists at long-term. The cause of the obesity paradox is probably multi-factorial. This offers potential for future research in order to improve outcomes for persons on both sides of the ‘optimum BMI’.

骨格筋のビタミンDの役割：形態、機能、代謝

骨格筋のビタミンDの役割：形態、機能、代謝に関するレビュー論文を紹介します。

Girgis CM, Clifton-Bligh RJ, Hamrick MW, Holick MF, Gunton JE. The roles of vitamin d in skeletal muscle: form, function, and metabolism. Endocr Rev. 2013 Feb;34(1):33-83. doi: 10.1210/er.2012-1012.

50頁もあるのでまだ抄録と図程度しか読めていませんが、この論文1本でビタミンDと筋肉・サルコペニアの基本的な知識は十分習得できるのではと感じます。ビタミンD欠乏でミオパチー、筋肉痛を生じることがありビタミンD投与で改善することや、筋力・身体機能と一定の関連があることは確かなようです。

ただビタミンDの骨格筋細胞内のシグナルやメカニズムはまだよくわかっていませんし、ビタミンDリセプターが十分に分化した成人の骨格筋に存在するかどうかやその生理学的重要性もわかっていないようです。ビタミンDが欠乏していてサルコペニアのときには投与すべきですが、課題が多いですね。

Abstract

Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of research and one that continues to extend the frontiers of knowledge of vitamin D's broad functional repertoire.

ベッド上安静時の飢餓は骨格筋分解を加速

少し前の論文ですが、2週間のベッド上安静時の飢餓は骨格筋分解を加速させるという論文を紹介します。

Biolo G, Ciocchi B, Stulle M, Bosutti A, Barazzoni R, Zanetti M, Antonione R, Lebenstedt M, Platen P, Heer M, Guarnieri G. Calorie restriction accelerates the catabolism of lean body mass during 2 wk of bed rest. Am J Clin Nutr. 2007 Aug;86(2):366-72.

下記HPで全文PDFで見ることができます。

http://ajcn.nutrition.org/content/86/2/366.full.pdf

若年健常者9人を対象に、ベッド上安静と非安静群、十分なエネルギー投与群と低エネルギー投与群（1日エネルギー消費量の80％程度）にわけて、介入前後でDEXAによる除脂肪体重の評価とロイシンの代謝を調査しました。

筋肉量のみ結果を示します。ベッド上安静＋低エネルギー投与群では他の組み合わせの3群と比較して、有意に除脂肪体重が減少しました（1.10 +/- 0.1 kg）。ちなみに非安静＋低エネルギー投与群では0.3 +/- 0.3kgの減少で、十分なエネルギー投与群では0.1～0.3kgの減少でした。

以上より、ベッド上安静の時の飢餓の合併は骨格筋分解を加速させるという結論です。飢餓で筋肉量が低下することも、安静臥床時の飢餓はさらに筋肉量を減少させることも当たり前ですが、それがきちんとエビデンスになっていることは知りませんでした。

飢餓の時にレジスタンストレーニングは禁忌だと言っていますが、筋肉量を維持するためにはベッド上安静も禁忌ですね。動いたほうが体重減少も筋肉量減少も少ないですし。もっとも飢餓の有無に関わらず、サルコペニア対策としてベッド上安静は禁忌です。

非安静群では日中立位ですごし、病棟内歩行が可能で、10分間のエルゴメーターを1日3回行っています。私は栄養状態が悪化する場合でも、廃用予防のため2メッツまでの活動と早期離床は制限せずに行うべきであるという2メッツ仮説を提唱しています。でも3メッツまでの活動なら制限しなくてもよいのかもしれませんね。

Abstract

BACKGROUND:

Muscle inactivity and low energy intake commonly occur in persons with acute or chronic disease, in astronauts during space flight, and during aging.

OBJECTIVE:

We used a crossover design to investigate the effects of the interactions of inactivity and calorie restriction on whole-body composition and protein kinetic regulation in 9 healthy volunteers.

DESIGN:

Lean body mass (LBM) was measured by using dual-energy X-ray absorptionmetry before and at the end of 14-d periods of bed rest (B) and controlled ambulation (A) in patients receiving eucaloric (E) or hypocaloric (H) (approximately 80% of total energy expenditure) diets. Whole-body leucine kinetics were determined at the end of the 4 study periods by using a standard stable-isotope technique in the postabsorptive state and during a 3-h infusion of a 0.13 g x kg LBM(-1) x h(-1) amino acid mixture.

RESULTS:

In the postabsorptive state, we found a significant (P = 0.04) bed rest x hypocaloric diet interaction for the rate of leucine oxidation, an index of net protein catabolism (A+E: 0.23 +/- 0.01; B+E: 25 +/- 0.01; A+H: 0.23 +/- 0.01; B+H: 0.28 +/- 0.01 micromol x min(-1) x kg LBM(-1)). Bed rest significantly (P < 0.01) decreased amino acid-mediated stimulation of nonoxidative leucine disappearance, an index of protein synthesis (A+E: 35 +/- 2%; B+E: 30 +/- 2%; A+H: 41 +/- 3%; B+H: 32 +/- 2%). B+H decreased LBM by 1.10 +/- 0.1 kg, which is significantly (P < 0.01) greater than the decrease seen with A+E, A+H, or B+E.

CONCLUSION:

Calorie restriction enhanced the catabolic response to inactivity by combining greater protein catabolism in the postabsorptive state with an impaired postprandial anabolic utilization of free amino acids.

日本の在宅高齢者のサルコペニアと機能低下

日本の地域在住高齢者のサルコペニアと2年後の機能低下の関連をみた報告を紹介します。谷本先生の研究です。

Tanimoto Y, Watanabe M, Sun W, Tanimoto K, Shishikura K, Sugiura Y, Kusabiraki T, Kono K. Association of sarcopenia with functional decline in community-dwelling elderly subjects in Japan. Geriatr Gerontol Int. 2013 Mar 3. doi: 10.1111/ggi.12037. [Epub ahead of print]

対象は地域在住（高槻市）の65歳以上の高齢者743人です。筋肉量評価にはBIAを用いています。機種はタニタの体組成計 マルチ周波数体組成計MC-190です。

http://www.tanita.co.jp/tanita/hp/productDetail.do?_productId=796&_isListBack=true

四肢骨格筋指数（AMI、四肢骨格筋量÷身長÷身長）を計算して、AMIが若年の2標準偏差以下の場合を筋肉量減少ありとしています。谷本先生の先行研究から、男性ではAMI7.0 kg/m2未満、女性ではAMI5.8 kg/m2未満を筋肉量減少のカットオフ値としています。

筋力は握力で、身体機能は歩行速度（11mの距離を通常速度で歩行して、中間の5mの歩行速度を算出）でそれぞれ評価しています。握力と歩行速度のカットオフ値は日本での先行研究がないという理由で、今回の研究の下位1/4から設定しています（実際のカットオフ値は不明です）。

サルコペニアの診断はEWGSOPの基準を用いて、筋肉量減少があり、筋力低下もしくは身体機能低下を認める場合としています。一方、筋肉量減少のみの場合と、筋力低下and/or身体機能低下のみの場合をintermediateとしています。

ADLは修正KatzADLスケール、IADLは老研式活動能力指標（TMIG-IC）でそれぞれ評価しています。今回の研究ではADL、IADL両方とも介助を要する場合を機能障害と判断しています。ADL、IADLをベースラインと2年後に評価して、サルコペニアとの関連を調査しました。

結果ですが、サルコペニアと診断されたのは男性7.8％、女性10.2％でした。このうち2年後にADLに介助を要するようになったのは、男性36.8％、女性18.8％でした。年齢、BMIで補正したロジスティック回帰分析では、サルコペニアは男女とも2年後のADL低下に有意に関連していました。

以上より、日本の地域在住高齢者では、サルコペニアの存在が2年後の機能低下に関連し、サルコペニアの予防対策は機能低下を防ぐために重要であるという結論です。

サルコペニアの早期発見・介入の重要性を示唆する素晴らしい研究だと思います。握力と歩行速度の実際のカットオフ値を知りたいところです。下方先生のサルコペニア簡易診断基準にある、握力男性25kg未満、女性20kg未満、歩行速度1.0m/s未満と近いかどうかですね。

健常に近い在宅高齢者ではサルコペニアの主な要因は加齢だと思います。一方、私がリハやNSTで見ている入院患者ではサルコペニア（広義、ミオペニア）の主な要因は栄養、廃用、疾患です。セッティングによって原因と程度に違いはありますが、どこでも適切な評価と対応が重要だと考えます。

Abstract

AIM:

The present study aimed to determine the association of sarcopenia, defined by muscle mass, muscle strength and physical performance, with functional disability from a 2-year cohort study of community-dwelling elderly Japanese people.

METHOD:

Participants were 743 community-dwelling elderly Japanese people aged 65 years or older. We used bioelectrical impedance analysis (BIA) to measure muscle mass, grip strength to measure muscle strength, and usual walking speed to measure physical performance in a baseline study. Functional disability was defined using an activities of daily living (ADL) scale and instrumental activities of daily living (IADL) scale at baseline and during follow-up examinations 2 years later. Logistic regression analysis, adjusted for age and body mass index, was used to examine the association between sarcopenia and the occurrence of functional disability.

RESULTS:

In the present study, 7.8% of men and 10.2% of women were classified as having sarcopenia. Among sarcopenia patients in the baseline study, 36.8% of men and 18.8% of women became dependent in ADL at 2-year follow up. From the logistic regression analysis adjusted by age and body mass index, sarcopenia was significantly associated with the occurrences of physical disability compared with normal subjects in both men and women.

CONCLUSIONS:

Sarcopenia, defined by muscle mass, muscle strength and physical performance, was associated with functional decline over a 2-year period in elderly Japanese. Interventions to prevent sarcopenia are very important to prevent functional decline among elderly individuals.

台湾の筋肉量・身体機能・握力

台湾での加齢による筋肉量減少と身体機能の関連をみた報告を紹介します。

Liu LK, Lee WJ, Liu CL, Chen LY, Lin MH, Peng LN, Chen LK.　Age-related skeletal muscle mass loss and physical performance in Taiwan: Implications to diagnostic strategy of sarcopenia in Asia.　Geriatr Gerontol Int. 2013 Mar 3. doi: 10.1111/ggi.12040. [Epub ahead of print]

筋肉量はDEXAで測定しています。骨格筋量の指標として除脂肪体重÷身長÷身長(LBM/ht2 )、四肢骨格筋量÷身長÷身長(ASM/ht2 )、骨格筋指数 (SMI%)の3つを計算して、身体機能との関連を検討しました。

結果ですが、加齢は身体機能低下と関連し、ASM/ht2とLBM/ht2は加齢で低下しましたがSMI%は低下しませんでした。男性では歩行速度低下との関連は、SMI%よりASM/ht2のほうが高かったです。

女性ではASM/ht2、LBM/ht2、SMI%のいずれも歩行速度低下と有意な関連を認めませんでした。一方、握力は男女とも筋肉量減少（ASM/ht2とLBM/ht2のみ）と強い相関を認めました。

以上より、骨格筋量は握力とは強い相関を認めるが、歩行速度との相関はあまり強くないという結論です。アジア人では骨格筋量の指標として四肢骨格筋量÷身長÷身長(ASM/ht2 )が最も望ましく、身体機能の評価は骨格筋量の測定とは別に必要です。

サルコペニアの診断基準はまだ統一されていませんが、やはり筋肉量、筋力（握力）、身体機能（歩行速度など）の3項目の評価は行うべきでしょう。DEXAで筋肉量を評価できる場合には、四肢骨格筋量÷身長÷身長(ASM/ht2 )を計算するのがよさそうです。

Abstract

AIM:

Skeletal muscle loss is a common feature of aging, and is associated with unfavorable outcomes. Although several indexes of skeletal muscle mass measurement have been developed, the most optimal index for sarcopenia diagnosis among Asian populations has remained unclear. The present study aimed to evaluate the relationship between skeletal muscle mass and physical performance among community-dwelling people in Taiwan.

METHODS:

Data of the I-Lan Longitudinal Aging Study (ILAS) were retrieved for study. Comparisons between demographic profiles, physical performance and skeletal muscle mass (measured by dual-energy X-ray absorptiometry) were carried out. Skeletal muscle mass expressed by lean body mass divided by squared height (LBM/ht2 ), appendicular muscle mass divided by squared height (ASM/ht2 ) and percent skeletal muscle index (SMI%) were compared between measurements of physical performance.

RESULTS:

Overall, the data of 532 participants (mean age 64.6 ± 9.5 years, male 53.0%) were retrieved for analysis. Age was associated with poorer physical performance, and decreased ASM/ht2 and LBM/ht2 , but not SMI%. Skeletal muscle mass (SMI%) was less significantly related to slow walking speed than ASM/ht2 in men. In women, all three muscle indexes showed no significant association between slow walking speed. In contrast, low handgrip strength was strongly associated with decreased skeletal muscle mass (measured by ASM/ht2 and LBM/ht2 , but not SMI%) in both men and women.

CONCLUSIONS:

Skeletal muscle mass was significantly associated with handgrip strength along with aging, but the association of skeletal muscle mass and walking speed was less significant. In sarcopenia diagnosis among Asian populations, ASM/ht2 should be the most suitable index for skeletal muscle mass measurements, and physical performance should be measured universally beyond measurements of skeletal muscle mass.

廃用性筋萎縮を緩和する栄養戦略

廃用性筋萎縮を緩和する栄養戦略に関するレビュー論文を紹介します。

Benjamin T Wall, Luc JC van Loon. Nutritional strategies to attenuate muscle disuse atrophy. Nutrition Reviews, Article first published online: 28 FEB 2013, DOI: 10.1111/nure.12019

廃用性筋萎縮では、1日0.5％程度の筋肉量が減少します。筋力低下は1日0.3～4.2%と幅が大きいですが、筋肉量以上に筋力のほうが低下するという報告が多いです。短期では筋蛋白分解も廃用性筋萎縮に貢献している可能性がありますが、10日以上では筋蛋白合成低下がメインです。

栄養戦略としては十分な蛋白質摂取、蛋白質・必須アミノ酸の投与が重要です。クレアチンやn-3脂肪酸が有用な可能性があります。ビタミンDは健常高齢者で血中濃度が正常な場合には筋力改善の効果はありませんが、欠乏時には有用です。

廃用性筋萎縮に対しては、無駄な安静臥床を避けることが一番の治療です。治療上どうしても安静臥床にせざるを得ない場合には、十分にエネルギー・蛋白質を投与して飢餓を合併させないことがさらなる筋萎縮予防のために重要と言えます。侵襲の異化期であればエネルギーはほどほどですが。

Abstract
Situations such as recovery from injury or illness require otherwise healthy humans to undergo periods of disuse, which lead to considerable losses of skeletal muscle mass and, subsequently, numerous negative health consequences. It has been established that prolonged disuse (>10 days) leads to a decline in basal and postprandial rates of muscle protein synthesis, without an apparent change in muscle protein breakdown. It also seems, however, that an early and transient (1–5 days) increase in basal muscle protein breakdown may also contribute to disuse atrophy. A period of disuse reduces energy requirements and appetite. Consequently, food intake generally declines, resulting in an inadequate dietary protein consumption to allow proper muscle mass maintenance. Evidence suggests that maintaining protein intake during a period of disuse attenuates disuse atrophy. Furthermore, supplementation with dietary protein and/or essential amino acids can be applied to further aid in muscle mass preservation during disuse. Such strategies are of particular relevance to the older patient at risk of developing sarcopenia. More work is required to elucidate the impact of disuse on basal and postprandial rates of muscle protein synthesis and breakdown. Such information will provide novel targets for nutritional interventions to further attenuate muscle disuse atrophy and, as such, support healthy aging.

進行がん患者に対する専門のリハ栄養チーム

専門のリハ栄養チームが関わった進行がん患者では体重増加が主観的な身体機能改善と関連するという論文を紹介します。論文の内容よりもリハ栄養チームのほうが気になります。

Parmar MP, Swanson T, Jagoe RT. Weight changes correlate with alterations in subjective physical function in advanced cancer patients referred to a specialized nutrition and rehabilitation team. Support Care Cancer. 2013 Feb 26. [Epub ahead of print]

マギル大学ではspecialized nutrition and rehabilitation teamがあります。本文に以下のようにあります。以下、引用です。

As a group, these patients often have severe nutritional and functional impairment as well as a range of related symptoms, and the CNR-JGH clinic uses a comprehensive interdisciplinary approach to assess and, where possible, control symptoms, combined with individualized dietary interventions and physical rehabilitation.

つまり、栄養介入とリハを同時に行っているということになります。心リハを除くとこのようなリハ栄養の取り組みは、海外では他にあまり聞いたことがありません。
がん悪液質（がん以外の悪液質でも）に対して、栄養も運動・リハも薬剤も含めて、多職種で包括的に対応するのがベストであることは明らかです。ただ、既存のチーム医療では包括的な対応が十分にできているとは言い難いです。リハ栄養チームが悪液質に対するチーム医療のモデルになればと思います。

Abstract

PURPOSE:

The aim of this study is to assess whether short-term weight gain correlates with improvements in subjective markers of quality of life and physical function in patients referred to a clinic for management of cancer cachexia.

METHODS:

A retrospective review of the records of 306 patients referred to a specialized multi-disciplinary supportive care team with particular interest in treating cancer cachexia. Weight changes between each of the first three clinic visits, were correlated with the corresponding changes in patient-rated performance status, perceived strength and quality of life. In a second cohort of 56 patients, the correlation between perceived strength and quality of life was re-tested using a more detailed quality of life tool.

RESULTS:

Even over short time intervals positive correlations were observed for weight change vs. change in patient-rated performance status (R (s) > 0.15, P < 0.05), and for changes in perceived strength vs. quality of life (R (s) > 0.33, P < 0.001). The correlation between changes in patient-rated strength and quality of life was consistent across all subgroups studied and was reproducible when using a different, validated, quality of life tool (FAACT) in a second independent patient cohort.

CONCLUSIONS:

Weight gains are associated with subjective improvements in physical functioning, and changes in perceived physical strength are consistently correlated with quality of life.

日本人高齢者のサルコペニア簡易基準案

日本人高齢者のサルコペニア簡易基準案に関する論文を紹介します。

下方浩史、安藤富士子．サルコペニア―研究の現状と未来への展望―1．日常生活機能と骨格筋量、筋力との関連．日老医誌2012;49:195-8.

下記HPで全文PDFで見ることができます。

https://www.jstage.jst.go.jp/article/geriatrics/49/2/49_195/_pdf

この簡易基準案では、普通歩行速度1 m/s未満、もしくは握力が男性25 kg未満、女性20kg未満である場合に脆弱高齢者と判断し、脆弱高齢者のうち，BMI 18.5 kg/m2未満もしくは下腿周囲長30 cm未満である場合をサルコペニアとしています。

この基準案なら在宅でもサルコペニアの診断が可能です。筋肉量減少の評価がサルコペニアの診断で常に課題となりますが、ここではBMI 18.5 kg/m2未満もしくは下腿周囲長30 cm未満をもって筋肉量減少に相当するものとしています。

今後、このサルコペニア簡易基準案で適切かどうか、信頼性、妥当性の検証が必要です。サルコペニアの診断基準がはっきりしないことには、適切な評価と対応が困難ですし、保険診療に含めれることも期待できません。EWGSOPの診断基準との比較も必要だと思います。

頸部筋肉量と脳容量・認知機能

健常高齢男性における頸部筋肉横断面積と脳容積と認知機能の関連をみた論文を紹介します。

Kilgour AH, Ferguson KJ, Gray CD, Deary IJ, Wardlaw JM, Maclullich AM, Starr JM. Neck muscle cross-sectional area, brain volume and cognition in healthy older men; a cohort study. BMC Geriatr. 2013 Feb 28;13(1):20. [Epub ahead of print]

正常加齢ではサルコペニアと年齢による認知機能低下が大きな問題です。先行研究で筋肉機能、認知機能、脳構造に正の関係があることは示されていますが、筋肉量を考慮した研究は少数です。そのため、頸部筋肉量と脳容積と認知機能の関連を調査しました。

対象は健常高齢者51人（平均年齢73.8歳）です。頸部筋肉量はMRIで測定しました。認知機能として記憶（視覚、言語）、遂行機能、推測されるもとの認知機能を評価し、脳容積はMRIで脳全体、海馬、小脳を評価しました。

結果ですが、頸部筋肉横断面積が大きいと脳全体の萎縮が有意に少なかったです。頸部筋肉横断面積は他の脳容積や認知機能とは有意な関連を認めませんでした。頸部筋肉横断面積が小さいと推測されるもとの認知機能が有意に高かったです。

サルコペニアと認知機能に関連があるかどうかは、今回の研究だけでは不明ですね。頭が重いほど頸部への負担が大きく頸部筋肉量も増えるでしょうし。栄養状態が著しく悪いと両者に影響を与えるでしょうし。縦断研究で交絡因子の十分な検討が必要だと思います。

Abstract

BACKGROUND:

Two important consequences of the normal ageing process are sarcopenia (the age-related loss of muscle mass and function) and age-related cognitive decline. Existing data support positive relationships between muscle function, cognition and brain structure. However, studies investigating these relationships at older ages are lacking and rarely include a measure of muscle size. Here we test whether neck muscle size is positively associated with cognition and brain structure in older men.

METHODS:

We studied 51 healthy older men with mean age 73.8 (sd 1.5) years. Neck muscle cross-sectional area (CSA) was measured from T1-weighted MR-brain scans using a validated technique. We measured multiple cognitive domains including verbal and visuospatial memory, executive functioning and estimated prior cognitive ability. Whole brain, ventricular, hippocampal and cerebellar volumes were measured with MRI. General linear models (ANCOVA) were performed.

RESULTS:

Larger neck muscle CSA was associated with less whole brain atrophy (t = 2.86, p = 0.01, partial eta squared 17%). Neck muscle CSA was not associated with other neuroimaging variables or current cognitive ability. Smaller neck muscle CSA was unexpectedly associated with higher prior cognition (t = -2.12, p < 0.05, partial eta squared 10%).

CONCLUSIONS:

In healthy older men, preservation of whole brain volume (i.e. less atrophy) is associated with larger muscle size. Longitudinal ageing studies are now required to investigate these relationships further.