COPDへのBCAA投与の効果

COPD（慢性閉塞性肺疾患）に対するBCAA（分岐鎖アミノ酸）投与の効果をみた最近の論文を2つ紹介します。いずれもイタリアの論文です。

対象者は少ないのですが、どちらの論文もランダム化比較試験で、BCAA投与群で体重の有意な増加を認めています（①は12週間のBCAA投与で12ヶ月後で6kg、②は12週間のBCAA投与で12週後で3.8kg）。

これだけ見るとCOPDの患者にはBCAA製剤を使用したほうがよい気になりますが、個人的な印象では体重増加の効果が大きすぎるように感じます。RCTではありますが、エビデンスの質の高い論文とは言いづらい気がします。

COPDに対する栄養療法はなかなか効果を出せなくて、最近になってようやく有効という論文が出始めている段階です。

なかなか効果が出ないのは、COPDによる栄養障害の場合、単なる飢餓（エネルギー摂取量不足）ではなく、悪液質を認めるからです。悪液質の早期発見、早期治療がCOPDの栄養管理では求められます。

そうすると、COPD患者には単にBCAAを投与すればよいのではなく、包括的呼吸リハの中で、薬物療法、運動療法、酸素療法、生活指導を同時に行い、さらに適切にエネルギー摂取量を確保しておくことが必要条件だと思います。

COPD患者にNSTが介入して、栄養管理（適切なエネルギー量投与）も含めた包括的リハを行っているのに、栄養改善が難しい場合には、BCAA投与を検討してよいと考えます。

①Dal Negro RW, et al: Comprehensive effects of supplemented essential amino acids in patients with severe COPD and sarcopenia. Monaldi Arch Chest Dis. 2010 Mar;73(1):25-33.

AIM: Aim of the study was to investigate whether or not oral supplementation of essential amino acids (EAAs) may improve body composition, muscle metabolism, physical activity, cognitive function, and health status in a population of subjects with severe chronic obstructive pulmonary disease (COPD) and sarcopenia. METHODS: Thirty-two patients (25 males) (FEV1/FVC < 40% predicted), age 75 +/- 7 years, were randomised (n = 16 in both groups) to receive 4 gr/bid EAAs or placebo according to a double-blind design. When entered the study (T0), after four (T4), and after twelve (T12) weeks of treatments, body weight, fat free-mass (FFM), plasma lactate concentration (micromol/l), arterial PaCO2 and PaO2, physical activity (n degree steps/day), cognitive function (Mini Mental State Examination; MMSE), health status (St. George's Respiratory Questionnaire; SGRQ) were measured. RESULTS: EAAs supplemented, but not patients assuming placebo, progressively improved all baseline variables overtime. In particular, at T12 of EAAs supplementation, body weight (BW) increased by 6 Kg (p = 0.002), FFM by 3.6 Kg (p = 0.05), plasma lactate decreased from 1.6 micromol/l to 1.3 micromol/l (p = 0.023), PaO2 increased by 4.6 mmHg (p = 0.01), physical activity increased by 80% (p = 0.01). Moreover, the score for cognitive dysfunction improved from 19.1 scores to 20.8 (p = 0.011), while the SRGQ score also improved from 723 to 69.6 even though this trend did not reach the statistical significance. CONCLUSIONS. A three-month EAAs supplementation may have comprehensive effects on nutritional status; muscle energy metabolism; blood oxygen tension, physical autonomy; cognitive function, and perception of health status in patients with severe COPD and secondary sarcopenia.

②Baldi S, et al: Fat-free mass change after nutritional rehabilitation in weight losing COPD: role of insulin, C-reactive protein and tissue hypoxia. Int J Chron Obstruct Pulmon Dis. 2010 Feb 18;5:29-39.

Abstract
BACKGROUND: Fat-free mass (FFM) depletion marks the imbalance between tissue protein synthesis and breakdown in chronic obstructive pulmonary disease (COPD). To date, the role of essential amino acid supplementation (EAAs) in FFM repletion has not been fully acknowledged. A pilot study was undertaken in patients attending pulmonary rehabilitation. METHODS: 28 COPD patients with dynamic weight loss > 5% over the last 6 months were randomized to receive EAAs embedded in a 12-week rehabilitation program (EAAs group n = 14), or to the same program without supplementation (C group n = 14). Primary outcome measures were changes in body weight and FFM, using dual X-ray absorptiometry (DEXA). RESULTS: At the 12th week, a body weight increment occurred in 92% and 15% of patients in the EAAs and C group, respectively, with an average increase of 3.8 +/- 2.6 kg (P = 0.0002) and -0.1 +/- 1.1 kg (P = 0.81), respectively. A FFM increment occurred in 69% and 15% of EAAs and C patients, respectively, with an average increase of 1.5 +/- 2.6 kg (P = 0.05) and -0.1 +/- 2.3 kg (P = 0.94), respectively. In the EAAs group, FFM change was significantly related to fasting insulin (r(2) 0.68, P < 0.0005), C-reactive protein (C-RP) (r(2) = 0.46, P < 0.01), and oxygen extraction tension (PaO(2x)) (r(2) = 0.46, P < 0.01) at end of treatment. These three variables were highly correlated in both groups (r > 0.7, P < 0.005 in all tests). CONCLUSIONS: Changes in FFM promoted by EAAs are related to cellular energy and tissue oxygen availability in depleted COPD. Insulin, C-RP, and PaO(2x) must be regarded as clinical markers of an amino acid-stimulated signaling to FFM accretion.