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Monday 24 September 2018

IGF-1: Miracle Hormone or Health Hazard?

Could a hormone produced in the body be the key to weight loss, increased muscle mass, health and longevity?
Some believe this could be the case with IGF-1, but others argue that supplementing with it comes with several harmful side effects.
This article explains what IGF-1 is, how it might affect our health, and whether supplementing with it is a good idea.

WHAT IS IGF-1?

IGF-1 stands for insulin-like growth factor 1, a hormone that regulates growth hormone levels.
It’s similar to insulin and works together with growth hormone to promote cell growth.
IGF-1 can be made in nearly every cell in the body. However, most is produced in the liver when growth hormone levels increase in the blood. In turn, IGF-1 levels also increase to slow down growth hormone production (1).
  
This balance between IGF-1 and growth hormone is critical to human growth and development. Abnormal IGF-1 levels can lead to various health problems:
  • Excessively high levels of IGF-1 at any stage in life can cause a rare condition known as acromegaly (gigantism).
  • Excessively low levels can cause a condition known as Laron Syndrome (dwarfism), which is usually diagnosed in childhood.
  • Chronically high and low IGF-1 levels increase risk of death in adults (3).
What Does IGF-1 Do?
IGF-1 is produced throughout your life but typically p eaks during puberty (45). 
Along with cell growth, IGF-1 also promotes cell survival and protects against cellular damage. The effects of this can be seen in several major organs (5).
It encourages fetal growth, central nervous system development, and proper function of the heart, kidneys and immune system. 
Because of its importance in growth and other key bodily functions, it’s crucial for IGF-1 levels to stay in proper balance.
Some people want to raise their IGF-1 levels because certain studies have suggested it may boost longevity and improve body composition. Meanwhile, those at risk for certain cancers are more interested in lowering their levels (578).
Summary: IGF-1 is a hormone typically made in the liver in response to growth hormone secretion. In addition to promoting cell growth and survival, It helps keep the brain, heart and kidneys healthy. It’s produced throughout life, but levels tend to fall off into adulthood.

TESTS FOR IGF-1 LEVELS

IGF-1 status can be checked with a simple blood test, though these are not routinely performed.
Physicians may check levels in children who are growing slowly, or when pituitary disorders or tumors are suspected.
It’s also sometimes used to check for malnutrition associated with certain health conditions, particularly in children and older adults (5).
IGF-1 is measured in nanograms (ng) per milliliter (mL). Normal values vary based on age and sex:
  • Ages 0-10: 14-495 ng/mL
  • Ages 11-17: 17-633 ng/mL
  • Ages 18-55: 37-245 ng/mL
  • Ages 55+: 25-232 ng/mL
Summary: Doctors typically check IGF-1 status when they suspect growth abnormalities,  pituitary dysfunction or malnutrition.

IGF-1, LR3 AND OTHER SUPPLEMENTS FOR BODYBUILDING

Bodybuilders and other athletes have shown interest in IGF-1 because it helps build muscle.
Interestingly, resistance training appears to increase IGF-1 activity, at least in middle aged women. But some bodybuilders supplement with IGF-1 in hopes of gaining more strength (79).

Deer Antler, IGF-1 LR3 and IGF-1 DES

There are a few popular IGF-1 supplements on the market including:
  • Deer Antler or Velvet Antler is derived from the velvety coating on deer antlers.
Deer antler is available in pill or spray form. Some types may contain small amounts of IGF-1, but it’s hard to know for sure because these supplements aren’t regulated.
Even if they do contain some IGF-1, they may not be very effective. The proteins in IGF-1 break down in the stomach, so it’s unlikely that much would reach the bloodstream (10).
  • IGF-1 LR3 (long arginine 3 IGF-1) is a form of IGF-1 with the amino acid arginine as the third protein in its gene sequence. It has a longer half life than IGF-1, which means that it stays active in the body for longer.
Unlike deer antler, IGF-1 LR3 is typically injected. It’s become a popular performance-enhancing drug because it’s very potent. Rodent studies have found it to be about 2.5 times more anabolic muscle-building than IGF-1 (11).
  • IGF-1 DES has a shorter protein sequence than IGF-1. It’s about 10 times more muscle-building anabolic than IGF-1 (12).
Like IGF-1 LR3, it’s become a popular drug among bodybuilders and athletes and is typically injected.
There’s no dose that’s medically been proven to be safe or effective for sports. Part of the reason why IGF-1 supplements are popular is that they’re difficult to detect in tests. This is because IGF-1 is made in the body.
Importantly, IGF-1 supplements are banned from competition and training by the World Anti-Doping Agency, the U.S. Anti-Doping Agency and other sports governing bodies.

IGF-1 Side Effects

IGF-1 supplements have been linked to serious side effects such as (713):
  • swelling of the extremities
  • low blood sugar
  • headaches
  • joint pain
  • heart enlargement
  • increased cancer risk
  • hormone dysfunction
  • acne.
IGF-1 supplements are not recommended for these reasons, despite online testimonials to their effectiveness.
Summary: IGF-1 supplements like Deer Antler, IGF-1 LR3 and IGF-1 DES have become popular among bodybuilders and athletes because of their muscle-building properties. These supplements are banned by many sporting regulatory agencies. They also have many potential side effects like swelling, headaches and increased cancer risk.

IGF-1 AND WEIGHT LOSS

Increasing IGF-1 is also of interest to those who want to burn fat.
However, any claims that IGF-1 can promote weight loss are largely theoretical, or based on animal studies and small human studies (14).
One large observational study linked low IGF-1 levels to higher body mass index (BMI) but couldn’t prove cause and effect (151617).
Another very small study looked at IGF-1 supplements for children with Laron dwarfism, which is known to cause excessive body fat.
Nine children received IGF-1 injections at doses of 150-200 milligrams per kilogram of body weight per day for at least 1 year. In addition to increasing height, treatment with IGF-1 reduced body fat even when body weight increased (17).
This indicates that IGF-1 may burn fat independent of total body weight, at least in the case of specific medical conditions. But given the tiny size and specificity of the study, we can’t use it to form recommendations for the general public.
Overall, supplementation of IGF-1 isn’t recommended for weight loss due to a lack of evidence and the likelihood of side effects. Try these weight loss strategies instead.
Summary: Observational studies have linked low IGF-1 levels with high body mass index. Therefore, increasing IGF-1 levels could, theoretically, promote weight loss, but much more research is needed to support this.

IGF-1 AND CANCER

Just as IGF-1 helps key cells reproduce and survive, it also promotes growth and survival in unhealthy cells. 
In addition to promoting cell growth, IGF-1 inhibits apoptosis (programmed cell death). These traits make it easier for cancer to spread throughout the body (7).
High IGF-1 levels have been linked to increased risk for gastrointestinal, prostate, ovarian and breast cancers (1819).
One study of 125 patients with colorectal cancer found significantly higher IGF-1 levels in those with more advanced cancers compared to those with lower grade cancers (20).
Another study found men with high IGF-1 levels to be 5.1 times more likely to develop advanced prostate cancer (21).
And one recent study saw significantly higher IGF-1 levels in women with ovarian cancer compared to healthy controls (22).
Lastly, a fourth study discovered that IGF-1 promoted the spread of specific types of breast cancer cells.
That said, results are mixed overall as to how much IGF-1 may affect breast cancer risk (22).
High levels of IGF-1 may also make it easier for certain types of cancer cells to withstand chemotherapy. This makes the disease more difficult to treat (23).
Some studies have explored treatments for cancer aimed at altering IGF-1 activity, but more research is needed.
Given that high IGF-1 levels may increase risk for certain cancers or make them more difficult to treat, it’s natural to wonder if you should try to lower your IGF-1 levels.
There’s evidence that certain foods or certain ways of eating may lower it, but this is really theoretical right now. We’ll discuss these in more detail in below sections.
Summary: IGF-1 promotes growth of all cells – even unhealthy ones. This means higher IGF-1 levels increase risk for certain cancers and make some more difficult to treat.

IGF-1 AND DIABETES

There’s been a lot of interest in the role of IGF-1 in diabetes because of its structural and functional similarities to insulin.
IGF-1 is thought to pull glucose out of the bloodstream and boost the effects of insulin (24,25).
One large observational study found higher risk for diabetes in younger adults with low IGF-1, but not in adults older than 65.
Interestingly, another large observational study linked both low and high IGF-1 levels to type 2 diabetes risk. More research is needed to clarify this paradox (2627).
Because of the links between IGF-1 and diabetes, some studies have looked at whether it can be used as a treatment for those who are low in it.
Several studies have found that IGF-1 can improve blood sugar control; however, it also has high rates of adverse side effects (25).
The role of IGF-1 in diabetes isn’t fully understood yet, beyond knowing that it’s best to have IGF-1 values in normal range. Small studies have found that low carbohydrate dietsmay help lower IGF-1 levels, but possibly not if animal protein is too high. We’ll discuss dietary factors in later sections of this article.
Summary: IGF-1 acts similarly to insulin and may be effective against diabetes. It’s long been argued that low IGF-1 increases diabetes risk, but some studies suggest the opposite. More research is needed to explain its role in diabetes.

IGF-1 AND FRAILTY FROM AGING

Some researchers believe there is a strong connection between IGF-1 and aging.
This is because IGF-1 production decreases throughout one’s lifespan. In fact, this pattern of aging is so common that some researchers refer to it as “somatopause”  (5).
Lower levels of IGF-1 and growth hormone in older adults have been linked with (514):
  • increased fat mass
  • increased cardiovascular risk
  • decreased muscle mass and strength
  • lower cognitive function
  • lower bone density
  • limited joint mobility
Several of these traits are seen in frail older adults.
A recent observational study looked at possible links between IGF-1 and frailty. In 1,833 adults aged 51 and older, those with higher IGF-1 levels had more muscle mass, higher bone density and stronger grip strength. Those with lower IGF-1 levels were found to be weaker (28).
These findings link low IGF-1 levels with certain measures of frailty, but the researchers weren’t able to prove a direct cause.
Summary: IGF-1 production declines with age. Some studies suggest that this may contribute to frailty and other medical problems common in older age.

CALORIE RESTRICTION AND IGF-1

 Calorie restriction may lower IGF-1.
This may be helpful for those at higher risk for certain cancers, at least in theory.
These arguments are largely based on rodent studies, which have found that prolonged fasting can reduce serum IGF-1 by up to 40% (18).
But a 2015 randomized control trial with 218 healthy adults found no direct links between calorie restriction and serum IGF-1 levels.
Researchers found a significant 21% increase in serum IGF binding protein-1—a protein that impacts IGF-1 activity—among those that reduced calories.
However, no significant differences in serum IGF-1 were seen among those who restricted calories after two years.
In other words, long-term calorie restriction doesn’t appear to directly reduce serum IGF-1 in humans (18).
In fact, it may even increase it slightly. One randomized control trial with 439 volunteers found slight increases in IGF-1 among overweight and obese women who lost weight by restricting calories (29).
Summary: Calorie restriction is often reported to lower IGF-1 levels, but studies have found this to be more the case in rodents than humans. In fact, some evidence suggests that long-term calorie restriction may even increase it a bit.

IGF-1 AND PROTEIN INTAKE

Small studies suggest that high protein intake—not high calorie intake—may be responsible for higher IGF-1 levels.
In one study in which calorie restriction failed to lower IGF-1 levels, researchers asked six volunteers to reduce their daily protein intake. Lowering protein by an average of 0.72 grams per kilogram of body weight per day resulted in an average decrease of 25% in IGF-1 (30).
These findings are consistent with other studies, like one that compared IGF-1 levels between 28 vegans and 28 members of the Calorie Restriction Society.
The vegans averaged 0.76 grams of protein per kilogram of body weight per day (roughly 10% of daily calories from protein), while the Calorie Restriction members averaged 1.73 grams (roughly 24% of calories from protein).
Serum IGF-1 levels were significantly lower in the lower protein group, independent of other factors like body weight and body fat (30). 
Taken together, these studies suggest that protein intake may need to be reduced along with calories to lower IGF-1 levels.
Summary: Long-term calorie restriction doesn’t appear to directly impact IGF-1 levels in humans, although it may make it less active. Instead, reducing protein intake may be more effective at lowering IGF-1 levels.

INTERMITTENT FASTING AND IGF-1

 Recent studies have looked at whether intermittent fasting might lower IGF-1 levels.
One of the most common intermittent fasting protocols is 16:8, which involves fasting for 16 consecutive hours per day.
In one small study of 34 resistance-trained men, half ate normally while the other half followed a 16:8 intermittent fasting diet. Calorie intake was similar between the two groups.
The intermittent fasting group saw significant reductions in IGF-1 after two months, with no change in the normal diet group.
Researchers aren’t sure exactly why intermittent fasting lowered IGF-1 levels in this study (31).
Animal studies have also found that intermittent fasting lowers IGF-1 more effectively than long-term calorie restriction, but other studies have found no difference between the two (3233).
More research is needed to know if intermittent fasting is a reliable way to lower IGF-1.
Summary: Intermittent fasting restricts eating to specific time periods. Some studies have found it to be effective in lowering IGF-1 levels, though it’s not fully understood how.

FOODS THAT MAY LOWER IGF-1

Certain foods and nutrients have also been reported to lower IGF-1, including green tea, lycopene and alcohol.

Green Tea

Green tea contains compounds called polyphenols that have long been thought to protect against cell damage.
In rodent studies, polyphenols from green tea significantly reduced IGF-1. Observational human studies have also found that green tea can reduce the risk of certain cancers by lowering IGF-1 production (3435).
More human studies are needed to know if green tea is helpful in reducing IGF-1 and, if so, how much is needed per day.

Lycopene

Lycopene is an antioxidant that’s found in foods like tomatoes and watermelon.
Observational studies have linked higher lycopene intake with lower prostate cancer risk.
Because high IGF-1 levels have been linked to increased prostate cancer risk, a handful of studies have looked at whether lycopene might lower IGF-1 levels (36).
In one randomized control trial of 97 men with low-grade prostate cancer, one group received 30 milligrams per day of lycopene, another 3 grams of fish oil per day, and another a placebo.
No significant differences were seen among the three groups after the three-month intervention. Other small human studies have found similar results (3637).
In other words, foods high in lycopene haven’t been shown to lower IGF-1 levels, but they may have other health benefits.

Alcohol

Acute and chronic alcohol intake have been found to lower IGF-1 levels (38).
In one study of 53 postmenopausal women, participants abstained from alcohol for 8 weeks, then drank one alcoholic beverage per night for 8 weeks, then drank two alcoholic beverages per night for 8 weeks.
One drink per night appeared to have very little effect on IGF-1; however, two drinks per night decreased it significantly, by 4.9% (39).
The study didn’t test if more alcohol led to further decreases in IGF-1. However, for overall health, those who already drink should limit alcohol intake to 1-2 drinks per night.
Summary: Small studies suggest that green tea, lycopene, and moderate alcohol intake may lower IGF-1 levels, but more research is needed.

FOODS AND NUTRIENTS THAT MAY INCREASE IGF-1

Most IGF-1 is produced within the body.
However, certain foods may indirectly increase production—at least in theory (13).

Carbohydrates

High carbohydrate diets increase insulin activity and may therefore increase IGF-1, which acts a lot like insulin.
In one study of 595 premenopausal women, participants who ate more carbohydrates had higher levels of IGF-1. This finding is consistent with other human and rodent studies (4041).
In another recent study, 71 healthy adults followed a diet that was low in carbohydrates, sugar and protein but high in saturated fats for five consecutive days per month.
IGF-1 levels decreased after three months. These effects were particularly strong among those at higher risk of aging-related diseases (42).
But cutting carbohydrates may not be the simplest solution, because higher protein diets have also been linked to increased IGF-1.
Instead, it’s best to eat carbohydrates in moderation and choose unrefined versions like fruits, vegetables, and whole grains whenever possible.
Dairy
Large observational studies have found higher IGF-1 levels in those who consumed more dairy products (4344).
There are a couple of possible mechanisms for this. Studies have found cow’s milk to contain IGF-1, so it can be ingested and absorbed.
It’s also been proposed that certain nutrients in dairy products can trigger production of IGF-1 in the body (45).
Until studies can prove the extent to which dairy increases IGF-1, there’s no reason to eliminate it from the diet completely.
Modest to moderate dairy intake is likely fine for healthy people without lactose intolerance.

Magnesium

Magnesium is a mineral that’s found in fruits and vegetables (especially green leafy vegetables), nuts and legumes.
One study of 399 men aged 65 and older found that those who ate more magnesium-rich foods had higher levels of IGF-1. 
This relationship was independent of other factors, such as body mass index and history of heart failure (46).

Zinc

Zinc is a mineral found in foods like meat, shellfish and poultry.
In a small clinical trial, 20 postmenopausal women with type 2 diabetes received 30 milligrams per day of zinc; a second group of 20 women received a placebo.
After three weeks, women who received zinc supplements saw significant increases in IGF-1, but only if they were low in it at the start of the study. There were no changes among women with normal IGF-1 levels at baseline (47).
Other studies have connected low zinc levels with low IGF-1 in both rodents and humans, even when calorie intake is adequate (54849).
Until the relationship between zinc and IGF-1 is clarified, it makes sense to aim for therecommended daily intakes.

Selenium

Selenium  is a mineral that’s found in meat, fish, poultry and nuts.
One study of 951 men and women aged 65 and older found significantly higher levels of IGF-1 among those who ate more selenium, independent of other factors like energy and alcohol intake (50).
Other observational studies have found similar relationships between selenium and IGF-1 (4351).
Animal proteins are some of the best sources of selenium. In fact, some researchers have suggested it may be selenium, not protein, that is responsible for increasing IGF-1.
Summary : Carbohydrates, dairy products, selenium, zinc and magnesium have all been shown to increase IGF-1. However, until more studies can establish direct links between these foods and IGF-1, intake should be based on recommendations for healthy adults or individualized based on health status.

SHOULD YOU SUPPLEMENT WITH IGF-1?

IGF-1 is crucial for growth through adolescence, and for cell health and survival throughout life.
It also plays several other important roles, like regulating blood sugar and keeping our organs healthy.
As such, it makes sense that low IGF-1 levels may cause health problems like diabetes.
But too much IGF-1 is just as bad. High IGF-1 may also be to blame for diabetes and is strongly linked to certain types of cancer.
This means it’s important to maintain balanced IGF-1 levels.
However, some people may want to increase or decrease their IGF-1 levels to increase quality of life in older adulthood, to boost muscle mass, to ward off diabetes, or to lower risk of some cancers.
It may be possible to alter these levels through diet or with supplements.
But until more research clarifies the relationship between nutrition and IGF-1, it’s best to eat a balanced diet that’s not too high in protein or calories.
And you’d probably do best staying clear of IGF-1 supplements like LR3, IGF-1 DES, and deer antler.
These are banned by many sporting organizations, show little proof of effectiveness, and often come with serious side effects.

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