目的

肌少症(sarcopenia)，是一种与增龄相关的肌肉质量减少和同时伴有肌肉力量和/或躯体功能下降的进行性老年综合征，可增加跌倒、骨折和低生活质量的风险，进一步导致虚弱、残疾和高死亡率。鉴于肌少症对老年人群健康和社会医疗资源带来的沉重负担，对肌少症及肌少症风险人群进行及时干预显得尤为迫切。本课题旨在研究水解乳清蛋白或添加β-羟基-β-甲基丁酸(β-hydroxy-β-methylbutyrate，HMB)的配方乳粉对肌少症及肌少症风险人群的干预作用。

方法

对北京市社区、养老机构对年满60岁及以上的老年群体进行招募，纳入肌少症或具有肌少症风险的个体，采用分层区组随机化方法，确保每位参与者被均等地分配到以下三个干预组中：水解乳清蛋白配方乳粉干预组 (Ew)、水解乳清蛋白联合HMB干预组 (Ew&h)，以及采用常规膳食的对照组 (C)。对于Ew和Ew&h干预组，受试者每日摄入50克配方乳粉 (日均水解乳清蛋白量达到13g)，分配在上午和睡前用温水冲服，一共持续90天。通过问卷调查、人体成分分析、躯体功能测试以及实验室检测获得相关数据。主要研究指标为肌肉质量，次要指标为握力、身体活动能力，以及肌少症风险、衰弱、营养评估等指标。

结果

在干预90天后，组间四肢骨骼肌质量的变化没有出现统计学差异。但是，E_w组的握力增加明显，左手平均增加7.0kg (比 Ew&h组多增加3.1kg，比C组增加4.6kg)，右手平均增加6.9kg (比Ew&h组增加2.7kg，比C组增加3.9kg)，差异有统计学意义，P值均＜0.05。步速的变化上，组间差异未达到统计学显著性。两个试验组干预前后自身对比，左、右手握力和步速显著改善(P均<0.05)，但是四肢骨骼肌质量变化并不明显。对照组在干预前后同样呈现左、右手握力轻微增加和步速变快的结果 (P均<0.05)。亚组分析显示，年龄在70岁以下 (OR=3.56，95%CI为1.58~8.03)、肌少症  (OR=2.00，95%CI为1.14~3.52)以及来自社区的受试者(OR=2.51，95%CI为1.20~5.26)均展现出统计学上显著的握力改善(P＜0.05)。肌少症患者与肌少症风险人群的IL-6、IL-10、hsCRP和TWEAK水平存在显著差异。多因素logistic回归分析显示，较高水平的促炎因子IL-6和TWEAK与肌少症风险增加呈显著正相关。较高水平的IL-9和TNF-α与肌少症风险增加呈显著负相关。具体而言，IL-6 (>1.54 pg/mL)和TWEAK (>840.93 pg/mL)分别与7.1倍和4.3倍的肌少症发生风险有关 (P < 0.05)，即IL-6 [OR = 7.1, 95% CI为(1.4, 36.5)]和TWEAK [OR = 4.3, 95% CI为(1.3, 14.4)]。调整混杂因素后，IL-6和TWEAK仍与较高的肌少症发生风险相关(P＜0.05)。炎症等生物标志物之间的相关性分析表明，IL-6和TNF-α之间存在强相关，而IL-6与其他标志物之间存在较弱的相关性。

结论

针对肌少症及肌少症风险人群，研究表明水解乳清蛋白配方乳粉能或添加HMB能有效增强肌肉力量。此外，高水平的炎症因子如IL-6和TWEAK与肌少症发生的风险增加显著正相关，提示炎症因子在肌少症进展中的作用。

Objective 

Sarcopenia is a pernicious geriatric condition characterized by the insidious decline in muscle mass, which coincides with a diminution in muscular strength and physical functionality. This phenomenon is intricately linked to an elevated risk of adverse outcomes including falls, fractures, and suboptimal quality of life, ultimately culminating in frailty, disability, and increased mortality rates. Recognizing the daunting pressures that sarcopenia exerts on healthcare and societal systems necessitates prompt and targeted interventions for individuals exhibiting signs of sarcopenia or at risk thereof.

The study aims to delineate the efficacies of a milk protein formula—hydrolyzed whey supplemented with or without β-hydroxy-β-methylbutyrate (HMB)—on combatting sarcopenia among those affected and at pre-symptomatic stages.

Methods 

This study targeted elderly individuals aged 60 years and above, recruited from both community settings and retirement institutions in Beijing, to encompass those diagnosed with sarcopenia and those deemed at risk for its development. Our approach to participant allocation employed a stratified block randomization method, ensuring equitable distribution among three intervention cohorts: hydrolyzed whey protein formula milk powder intervention group (Ew), hydrolyzed whey protein accompanied by β-hydroxy-β-methylbutyrate (HMB) intervention group (Ew&h), and a conventional diet control group (C).

Participants in the Ew and Ew&h groups were each administered 50 grams of the formula milk powder daily, equivalent to a dose of up to 13 grams of hydrolyzed whey protein per day. This regimen was prescribed to be consumed with warm water, either in the morning or prior to bedtime, for a continuous period of 90 days.

Data collection encompassed a variety of methods: detailed questionnaires, comprehensive body composition analysis, physical functionality assessments, and laboratory-based tests. The primary outcome measure centered on assessing muscle mass, complemented by secondary metrics that included grip strength, level of physical activity, risk of sarcopenia, frailty, and nutritional status evaluations.

Results

No significant differences in the change of skeletal muscle mass in the extremities were observed after a 90-day intervention period. However, the grip strength in the experimental group Ew (Elderly with nutrition intervention) notably increased. Specifically, the average increase in grip strength was 7.0 kg for the left hand (compared to an increase of 3.1 kg and 4.6 kg in the Ew&h group and control group C, respectively), and 6.9 kg for the right hand (2.7 kg and 3.9 kg compared to the Ew&h group and control group C, respectively). These increases were statistically significant, with P values < 0.05.

Neither the changes in muscle mass nor those in gait speed reached statistical significance. However, both the grip strength and walking speed for the left and right hands were significantly improved in the two experimental groups (all P < 0.05), with no substantial changes observed in limb skeletal muscle mass. The control group also demonstrated a moderate increase in grip strength and gait speed before and after the intervention (all P < 0.05).

Subgroup analysis showed that subjects younger than 70 years of age (OR=3.56, 95%CI: 1.58-8.03), with sarcopenia (OR=2.00, 95%CI: 1.14-3.52), and from the community (OR=2.51, 95%CI: 1.25-3.52) were more likely to have sarcopenia. 95%CI 1.20-5.26) showed statistically significant improvement in grip strength (P < 0.05). Notably, patients with sarcopenia exhibited significant differences in their IL-6, IL-10, hsCRP, and TWEAK levels compared to those at risk of sarcopenia.

Multivariate logistic regression analysis demonstrated that higher levels of proinflammatory cytokines IL-6 and TWEAK were significantly and positively associated with an increased risk of sarcopenia, whereas higher levels of IL-9 and TNF-α were inversely correlated with this risk. In particular, elevated levels of IL-6 (>1.54 pg/mL) and TWEAK (>840.93 pg/mL) corresponded to a 7.1-fold and a 4.3-fold increased risk of sarcopenia, respectively (P < 0.05). Adjusting for confounding factors, IL-6 and TWEAK remained linked to a heightened risk of sarcopenia (P < 0.05). Finally, correlation analysis disclosed a robust correlation between IL-6 and TNF-α but weaker associations with other biomarkers.

Conclusions

For individuals at risk of sarcopenia, research indicates that consumption of hydrolyzed whey protein formula milk powder or supplementation with β-hydroxy-β-methylbutyrate (HMB) can significantly boost muscle strength. Effective intervention outcomes are more probable among participants under 70 years of age, with preferences for a vegetarian beverage regimen, elevated body fat levels, and compromised protein intake. Furthermore, elevated levels of pro-inflammatory cytokines such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-like Weak Inducer of Apoptosis (TWEAK) are notably positively correlated with an escalated risk of sarcopenia, implying their substantial role in its progression.

【Keywords】

Older adults; Nutrition intervention; Hydrolyzed whey Protein; β-hydroxy-β-methylbutyrate; Sarcopenia