Why protein restriction for longevity makes no sense

Here’s my current opinion: The data supporting protein restriction for longevity is not strong and must be contrasted against known detriments of protein restriction with ageing (like sarcopenia and frailty).

Here’s my caveat: This doesn’t mean that you need to eat a high-protein diet. That’s a false dichotomy.

Now I’ll explain why.

Of mice and men

One of the major issues with the literature surrounding protein restriction for longevity is that it comes mostly from studies in mice, which are not appropriate models for extrapolating effects in humans.

The cells of mice and humans use similar molecular mechanisms to regulate growth, replication, aging, and death, which is one reason why mouse models are used to study human diseases and ageing processes.

Another reason that mice are used, especially for research into ageing, is because their average lifespan is about 24 months (max of 48 months), far shorter than the 80-year average of humans (max of 120 years).^​1​

1 day for mice = 40 days for humans

Of course, the correlation changes based on the developmental period:^​1​

• Mice pups are weened after 28 days, compared to 6 months for a human infant, so 1 mouse pup day = 6.5 infant days.
• Mice attain puberty around 42 days, compared to 11.5 years for human children, so 1 mouse day = 100 children days.
• Mice become adults after 8–12 weeks (average of 10), compared to 20 years for a human, so 1 mouse day = 104 adolescent days.
• Mice become infertile around 15 months, compared to 51 years for a human woman (menopause), so 1 mouse day = 41 adult days.
• Mice are “elderly” for about 6 months, compared to 29 years for the post-menopausal woman, so 1 mouse day = 58 elderly days.

No matter what stage of life you look at, it is clear that any intervention in mice showing an effect will require a significant amount of time to occur in humans, if it occurs at all.

One reason for this difference in lifespan is owed to differences in metabolism. Mice have an energy expenditure rate per unit of body mass that is seven times greater than humans.^​2​ Mice lose 12–17% of their body weight after a 12–18-hour fast; up to 30% of their body weight after 72 hours; and die after 5 days of fasting.^​3​

Metabolic stability

“When it comes to studying ageing and the means to slow it down, mice are not just small humans.”^​4​

The metabolic stability–longevity principle posits that dietary restriction increases lifespan by increasing the stability of metabolic networks.^​4​ This principle fits nicely with the theory that ageing is owed to an accumulation of damage over time.^​5​ Damage causes instability.

There are many causes of damage; oxidative damage is one source that plays an important role.^​5​ Protein restriction reduces levels of oxidative damage, helping explain its link to longevity.^​6​

However, the low mass-specific metabolic rate of humans means less oxidative stress and a better ability to maintain cellular balance compared to the high mass-specific metabolic rate of mice.^​4,7​ Logically, then, mice will be more responsive to any intervention that reduces oxidative stress (like protein restriction).

When researchers attempt to extrapolate to humans the longevity effects of protein restriction in mice, they find that consuming a diet of 12% protein from 18-years onward will add a meager 3 years to life.^​8​

Protein requirements with ageing

So, you consume a diet of 12% protein, or about 60 grams if you eat 2,000 calories per day, which is around 0.8 g/kg for the typical adult.

You can read about my protein recommendations here.

Older adults require at least 1.2 g/kg of protein daily,^​9–11​ and several authorities now recommend older adults consume 1.2–1.5 g/kg.^{​12–14​}

The elderly require more protein to offset sarcopenia, which is defined as an impairment of physical function (walking speed or grip strength) combined with a loss of muscle mass.^​15​

Sarcopenia is the primary cause of frailty with aging,^​16​ which itself is associated with a higher risk of having disabilities that affect your ability to perform daily activities of living,^​17​ having to go to a nursing home,^​18​ and experiencing fractures,^​19​ falls,^​20​ and hospitalizations.^​21​ 

Collectively, the link between sarcopenia, frailty, and associated morbidities may explain why sarcopenia is associated with a greater risk of premature death and reduced quality of life.^​22,23​

A low protein intake is associated with frailty and worse physical function than a higher protein intake.^​24,25​ Accordingly, it makes no sense to restrict protein intake for longevity, since that increases the risk of dying prematurely.

Moreover, even if lifespan was increased (by that 3 years), would it be worth impaired physical function, reduced quality of life, and the fear of falls and fractures?

Of monkeys and men

There are longevity trials in rhesus monkeys, which are certainly a better model than mice. However, many of the same limitations apply.

Rhesus monkeys sexually mature at 3–5 years of age, have an average lifespan of 25 years, and have a max lifespan of about 40 years.^​4​ Hence, rhesus monkeys have a weaker metabolic stability than humans, meaning that any longevity effects will still be significantly more pronounced than any changes that may occur in humans.

Even so, among the 2 studies conducted, average lifespan was increased among only one of them.^​26​ Subsequent evaluation of the contrasting results revealed that the lifespan extension was best explained by a lifespan decrease in the control group because of a bad diet and overfeeding, rather than by a lifespan increase in calorie-restricted animals.^​26​

No study in rhesus monkeys has looked at longevity from protein restriction alone. Nonetheless, if these results can be translated to humans, it would mean that no beneficial effect of calorie restriction on lifespan can be expected in normal-weight or lean people, but that overweight and/or obese people could benefit to some extent from a decrease in excessive food intake.

But we already knew that weight loss in overweight and obese people benefit lifespan and health. And guess what? The protein intake required to optimize fat loss and body composition in this population is greater (1.2 to 1.5 g/kg body weight) than that promoted for longevity (0.8 g/kg or less).^{​27–30​}

Let’s not forget about genetics

Although not specific to protein restriction, a meta-analysis of 72 studies in mice looking at how some form of dietary restriction impacted lifespan found highly variable results depending on strain and genotype.^​31​

In B6 mice, for example, 21 studies found average lifespan to range from a 32% decrease to a 27% increase.^​31​

As another example, one study tested how a 40% restriction in energy intake affected the lifespan of 41 ILSXISS mouse strains.^​32​ The “longevity” diet actually shortened life in more strains than it lengthened, with the magnitude of change ranging from a loss of 700 days to a gain of 400 days.

If you plan to extend your lifespan with protein restriction, you better hope you have the right genetics.

What about the Blue Zones?

The Blue Zones are populations that have above-average longevity, including some of the longest lived people on Earth.

Surveys of the Blue Zone residents report some common lifestyle characteristics, like family coherence, avoidance of smoking, a plant-based diet, moderate and daily physical activity, and social engagement throughout the community.^​33​ This is in stark contrast to the chronically stressed, sedentary, and socially isolated Westerner who eats a nutritionally void and energy-dense diet based on processed grains, meats, and oils. 

While it is tempting to draw conclusions about diet from Blue Zone societies, it is impossible given the numerous other lifestyle factors so vastly different from the modern Western world. We also can’t forget the very important genetic component, already discussed.

IGF-1

Since a major goal of protein restriction is to reduce IGF-1, it is notable that at least one study in bodybuilders has shown that IGF-1 declines during contest preparation despite a high protein intake (2.7 g/kg).^​34​

So, do we need to restrict protein intake? It seems that energy restriction may be more important. Perhaps we can obtain the best of both worlds by ensuring adequate protein intake alongside energy restriction.

Summing up

The data supporting protein restriction for longevity is not strong. Mice are not appropriate models for extrapolation to humans due to differences in lifespan and metabolism; data in monkeys does not support a benefit of energy restriction on lifespan; there are unknown influences of genetics.

The weak longevity data we have must be contrasted against the far stronger data showing detriments of protein restriction with aging, like sarcopenia and frailty, reduced quality of life, and premature death.

References