Muscle as an Organ (Grip Strength & Myokines)

What grip strength measures

A hand dynamometer is a grip with a spring and a display. You squeeze as hard as you can, and the device shows kilograms. This simplicity is the reason the measurement was possible in cohorts with six-figure numbers of participants.

The PURE study, written out Prospective Urban Rural Epidemiology, had 139,691 people in 17 countries, from poor to rich, squeeze the device and then observed who died. For every 5 kilograms less grip strength, all-cause mortality rose by 16 percent, hazard ratio 1.16 with a confidence interval of 1.13 to 1.20. For cardiovascular death it was 17 percent, and likewise 17 percent for death from other causes.

The breadth of the signal is remarkable: heart attack was at 7 percent, stroke at 9 percent, and the strongest association was with all-cause mortality. Grip strength is not a heart marker but a gauge of the condition of the whole organism.

Stronger than blood pressure, but only for one question

The statement that grip strength predicts mortality better than blood pressure is correct if taken precisely. For death from any cause, grip strength per standard deviation has a hazard ratio of 1.37, systolic blood pressure 1.15. For new-onset cardiovascular disease this reverses: blood pressure 1.39, grip strength 1.21. These are two questions, and the difference disappears in almost every abbreviated retelling.

What grip strength did not predict is also revealing: no significant association with new-onset diabetes, with hospital admissions for pneumonia or COPD, with fall injuries or with fractures. That falls of all things are missing is surprising. A metric with clear limits is more credible than one that predicts everything.

Strength says more than mass

The Health ABC cohort put both side by side in the same people: 2,292 participants between 70 and 79 years of age, observed for almost 5 years, strength by dynamometer for knee extension and grip, mass by computed tomography of the thigh and DXA.

Strength clearly predicted mortality, for thigh strength per standard deviation with a hazard ratio of 1.51 in men and 1.65 in women. Muscle size, by contrast, was barely associated with mortality. The real proof lies in the adjustment: when muscle area was adjusted for, almost nothing changed in the association between strength and mortality. So strength did not act through mass. For a field that measures upper-arm circumferences, this is uncomfortable.

Muscle as a gland

The basic idea behind “muscle as an organ” is good physiology: under exertion, muscle releases signaling substances that act on adipose tissue, liver and brain. They are called myokines, and for interleukin 6 the exertion-dependent increase is undisputed.

The best-known representative is nonetheless a lesson in caution. Around 2013, irisin was the star: a messenger that was supposed to turn white fat into brown fat and carry the effect of exercise in molecular form. In 2015, a paper in Scientific Reports examined the 4 commercial antibodies used to measure irisin in the blood. All four reacted strongly with non-specific serum proteins, and no band was found at the expected molecular size in real samples. Test kits from different manufacturers differed by a factor of 18 on average.

That is not the last word. Since then there have been studies with better methods, including mass spectrometry, that detect irisin, and an ongoing debate.

What has been tested in randomized trials

There is one randomized trial, and it is called LIFE. 1,635 older people, average age 78.9 years, a good two thirds of them women. One group received a structured exercise program of moderate intensity, twice a week at the center and 3 to 4 times at home. The comparison group did not get nothing, but workshops and stretching exercises.

Over an average of 2.6 years, the endpoint of major mobility disability was counted, defined as the inability to walk 400 meters. It occurred in 30.1 percent of the exercise group and 35.5 percent of the comparison group. Hazard ratio 0.82 with a confidence interval of 0.69 to 0.98, p equal to 0.03. That is 18 percent in relative terms and 5 percentage points in absolute terms.

What the studies show

PURE, 139,691 people in 17 countries

Prospective observational study with grip strength measured by hand dynamometer. For every 5 kilograms less grip strength, all-cause mortality rose by 16 percent (1.16; 1.13 to 1.20), cardiovascular death by 17 and death from other causes likewise by 17 percent.

Health ABC, strength versus mass

2,292 people between 70 and 79 years of age, observed for almost 5 years. Thigh strength per standard deviation was at 1.51 in men and 1.65 in women, muscle size barely mattered. After adjustment for muscle area, the association remained unchanged.

LIFE, randomized exercise program

1,635 older people, average age 78.9 years, training versus an active comparison program. Over 2.6 years, major mobility disability occurred in 30.1 versus 35.5 percent, hazard ratio 0.82, p equal to 0.03.

Methodological criticism of irisin measurement

4 commercial antibodies, 2015 in Scientific Reports. All four reacted with non-specific serum proteins, the band at the expected size was missing in real samples, and kits from different manufacturers differed 18-fold on average.

Where the data stop

The biggest reservation concerns the direction. Grip strength is above all an indicator, not a lever. Anyone who becomes ill loses strength, often before the illness becomes noticeable: a tumor, incipient heart failure or silent inflammation eats away at muscle strength first. Anyone who trains their grip strength improves their grip strength. Whether that lowers their risk of death is something an observational study cannot say.

Also open is the myokine narrative as a product promise: the chain that exercise works through a particular myokine and that taking it is therefore enough has not been closed anywhere. And even LIFE can only be read within limits. What has been shown is the preservation of walking ability over 2.6 years in very old people, not a longer lifespan.

Status, approval and legal

This is about a measurement and about training, not about a product requiring approval. Hand dynamometers are freely available and cost 20 to 30 euros; grip strength measurement has long been part of routine assessment in geriatric medicine, and there is no doping relevance. Products advertised with myokines, on the other hand, sell a chain that has not been closed. For measurement at home: devices and protocols differ, and comparison with your own value from 2 years ago carries further than comparison with other people’s norm tables.

Safety

Training of the kind tested in LIFE was followed in a randomized trial over 2.6 years, in people with an average age of 78.9 years. Anyone over 40 who has had a long break is nonetheless better off starting with guidance and low intensity than with a maximal attempt. For grip strength itself, the most important note is not a training note: if this value falls without you training less, it should be checked by a physician.

Sources

• PURE study, The Lancet 2015
• Health ABC cohort: strength, but not muscle mass, is associated with mortality — Newman et al., 2006, 2,292 participants aged 70 to 79
• LIFE study — Pahor et al., JAMA 2014, 1,635 participants
• Irisin as a myth rather than an exercise-induced myokine — Albrecht et al., Scientific Reports 2015