Lower IGF-1 with Food

Lower IGF-1 with Food

In mice, protein restriction leads not only to a longer life, but also to less frailty and better physical performance later in life. It is suspected that FGF21 produces this benefit, because in mice that were modified so that they could not express FGF21, all anti-aging effects of protein restriction disappeared. In humans, other pathways of aging may be involved. Diets with excess protein can be associated with increased oxidative stress and inflammation, as well as a lower NAD+ level, which is crucial for sirtuin function. Reduced protein intake can also lower IGF-1 levels in the blood.

Low IGF-1 levels predict life expectancy in exceptionally long-lived people. Remember that people who had low IGF-1 levels from birth practically didn’t get age-related diseases like cancer? IGF-1 appears to mediate the beneficial effect of fasting in cancer, and when IGF-1 levels drop during fasting, that causes differential protection of normal cells compared to cancer cells, which strengthens chemo in killing cancer cells while sparing normal cells. We know this because restoring IGF-1 levels was enough to negate the protective effect of fasting. Starved cancer cells are more susceptible to chemo in vitro, but this effect disappears when the reduced IGF-1 in the Petri dish is replenished.

A few days of fasting can cut IGF-1 levels in half, but that is mainly because you take in less protein. In humans, protein—especially animal protein—in the blood is a key factor for IGF-1 levels. Women and men who ate a strictly plant-based diet had significantly lower IGF-1 values than those who ate a conventional diet, including comparatively lean participants (long-distance runners). And not because they consumed fewer calories, because when it comes to lower IGF-1 values, people eating plant-based even outperform the aforementioned CRONies, the members of the Calorie Restriction Society, who intentionally eat even fewer calories to live longer.

In mice, calorie restriction alone lowers IGF-1 levels, but humans also need a reduction in protein. Even in people practicing rigid, long-term calorie restriction, IGF-1 levels remain elevated. As already mentioned, it is suspected that it is due to protein, because if you lower their protein intake from 1.67 grams per kilogram of body weight per day to 0.95 grams, their IGF-1 values drop by more than 20 percent after three weeks. IGF-1 is cited as a reason why reduced protein intake may be an important element of an anti-aging and anti-cancer diet.

Potential downside of low IGF-1

For at least 20 years, a whole-food, plant-based diet has been recommended to slow the human aging process by lowering IGF-1. IGF-1 also appears to have a causal relationship with cancer, heart disease, diabetes, and osteoarthritis, so it could be responsible for a variety of beneficial effects of plant-based eating. People who, due to birth conditions, have lower IGF-1 levels for their entire lives also perform better cognitively. In see.nf/igf1bp I show in detail that lowering IGF-1 in people with high blood pressure can nevertheless also have a downside. So anyone who wants to eat less animal protein should keep a particularly close eye on their blood pressure and eat fewer ultra-processed foods and salt, and instead eat more potassium-rich foods such as beans, sweet potatoes, and dark green leafy vegetables.

Protein Restriction

The evidence that protein restriction extends lifespan is even older than the evidence from studies that reduced calories. The data on whether protein restriction or calorie restriction carries more weight are contradictory, but a comprehensive comparative meta-analysis of more than 100 studies of dietary restriction in dozens of animal species found that, for longevity, protein reduction is more important. Sometimes, however, it is difficult to tease out the result. If, for example, studies show that mice that get only 70 percent of their normal amount of food live longer, this may be attributed to calorie restriction, even though protein intake was reduced by the same proportion. On the other hand, studies of “protein restriction” in which mice receive less protein in their chow may show no beneficial effect because the animals compensate by eating more of the unlimited food, so that in the end they do not actually consume less protein.

In what is to date the most impressive study, researchers attempted to isolate these factors by randomizing nearly 1000 mice and assigning them to one of 25 diets that systematically differed in protein, carbohydrate, fat, and calorie content. The study found that the diet variants with the lowest protein/carbohydrate ratio led to the longest maximum lifespan regardless of calorie content. Markers of health in aging, including blood pressure, cholesterol, mitochondrial function, insulin sensitivity, and immune defense, were also best on a low-protein diet and worst on a high-protein, high-fat diet. A low-protein, high-carbohydrate diet yields the same benefits for metabolism and immune defenses as up to a 40-percent calorie restriction, and that without any restriction of calories. As protein levels fell, average lifespan rose from about 95 weeks to 125 weeks—an about 30 percent longer lifespan even with unchanged calorie intake.

Restricting protein, not calories, leads to higher life expectancy. In fact, researchers found that it appeared to shorten lifespan when only calories were reduced. How can this be reconciled with earlier mouse studies from the same breeding stock that found the opposite? In the new mega-study of 25 diet variants, a novel method of restricting calorie intake was used. The researchers designed all diet variants so that the mice could eat as much as they wanted. But how can you restrict calorie intake if the animals are allowed to eat ad libitum? The calorie-restricted variant was mixed with indigestible cellulose (mostly sawdust), so that a 30 percent calorie deficit still remained when the mice had eaten their fill. But despite calorie restriction, they did not live longer, but shorter.

How can the different results with the same calorie intake be explained? Perhaps the usual effect of calorie restriction is actually more an effect of intermittent fasting. In contrast to the cellulose-diluted chow, which the mice can eat whenever they want, when you set out only a fraction of the normal amount of food for them, the animals have to fast until the next day once they have eaten their daily ration. Could it be that the conventional benefits are instead due to hunger signals in the brain that you can achieve by restricting the amount of food, but perhaps not by diluting the chow? Or perhaps the usual calorie restriction also reduces protein intake, and that is the real reason for longevity.