Discover the Lean Body Hormone
by Bill Sardi: 2012
Presidential Election: Is†America Boxing Itself Into a†Corner?
Since its initial
discovery in 2000 by researchers in Japan, the hormone known as
growth factor-21 (FGF21) has intrigued biologists and endocrinologists.
Mouse FGF21 is highly identical to human FGF21, making it useful
for laboratory comparison.
take long for investigators to realize FGF21 is a "novel
therapeutic agent for human metabolism" in the regulation
of sugar utilization, particularly in fat cells (adipocytes) in
the liver. Therapeutic provision of FGF21 to laboratory mice reduces
blood sugar levels and these animals are resistant to obesity. And
FGF21 does not induce hypoglycemia (low blood sugar), cancer or
weight gain at any tested dose in diabetic or healthy animals. Biologists
were beginning to think of it as an ideal hormone/drug to treat
activity exhibited by FGF21 was found to be dependent
upon a gene called Klotho that makes beta-klotho protein that
in turn increases the ability of cell receptors for FGF21 to direct
its beneficial effects upon fat cells in particular.
also discovered that FGF21
interplays with a metabolic pathway called PPAR (peroxisome
proliferator-activated receptor) that aids in the transport of sugar
to fat cells and the burning of fat. Since an energy supply is essential
for life to be maintained, researchers were elated to find that
to maintain energy in living cells during starvation or fasting.
This makes FGF21 a necessary hormone to facilitate hibernation in
animals since they obviously donít consume food during that time.
How it works
of fasting, starvation or hibernation, cells must still produce
energy or die. When food
is withheld from animals for 12 hours or longer, liver cells
produce FGF21. Researchers found that FGF21
switches the body to a fat-burning mode and allows the body
to fuel itself with stored fat during times of food deprivation.
FGF21 mobilizes lipids from fat cells and directs the liver to transform
those energy-rich molecules to circulate throughout the body. Just
the provision of FGF21 by itself produces the same biological responses
as fasting without having to deprive calories.
says FGF21 has "almost
magical properties" as it improves insulin efficiency,
lowers circulating levels of cholesterol and trigylcerides and averts
age-related weight gain.
were not only beginning to think FGF21 is a remedy for diabetes,
but it could also prevent obesity after it was found that administration
of FGF21 to laboratory mice resulted in a 20% reduction in weight.
A human population
study finds that elevated
blood serum levels of FGF21 are associated with abnormal blood sugar
metabolism and insulin resistance seen among patients with metabolic
disease (diabesity). However, it should not be misconstrued that
increased amounts of FGF21 induce metabolic disease. It just means
hormone is increased as metabolism goes haywire.
FGF21 by drug companies ensued as pharmacologists began to make
FGF21 look-alike molecules (analogs) in hopes of producing "superior
metabolic" action. FGF21 could become the most advanced
weapon against diet-induced diseases ever imagined.
an anti-aging agent?
But then investigators
gleefully found that FGF21
also inhibits growth hormone. That would also place FGF21 in
a class of potential anti-aging molecules. Of interest, vitamin
D increases Klotho protein to regulate calcium and phosphate
in the body and thus also serves
as an anti-aging agent. FGF21 requires klotho protein to function.
Two known anti-aging agents were found to work in tandem.
were very tantalizing for researchers. They didnít want to jump
to conclusions. They needed a lifespan study. Laboratory mice live
about 12-18 months.
at University of Texas Southwestern Medical Center in Dallas launched
a study to determine if in fact FGF21 will prolong the life of laboratory
mice. Their efforts exceeded expectation. But their investigation
also wiped the biological drawing board clean and forced biologists
to re-think everything they have learned in the past decade.
genetically altering laboratory mice so they produce about 5-10
times more FGF2 during fasting resulted in a striking increase in
lifespan without reducing food intake. These super-mice
lived about 36% longer than normal mice and astoundingly better
than 30% of the female mice in the study were still alive at 44
months of age when the study was finalized. The risk of death was
reduced by 65% in male animals, 88% in females.
apparently burned away their fat much more efficiently. The revved-up
FGF21 mice were leaner than normal mice even though they ate about
the same amount of food.
But all this
was accomplished without
activating other well-known longevity pathways (sirtuin genes,
AMP kinase, mTOR and NAD+). Unexpectedly, calorie restriction, known
to double the lifespan of laboratory animals by cutting caloric
intake in half, did not trigger FGF21 hormone production.
altered mice are smaller than normal mice as they produce less growth
factor (insulin-like growth factor 1 or IGF1). While life-prolonging
calorie restriction significantly alters 831 genes in laboratory
mice, FGF21-producing mice achieved super-longevity by
altering only a small number of genes (33).
Wow, it first
appeared humanity was on the cusp of a giant breakthrough that could
promote health and prolong life beyond any prior imagined mechanism.
But there was one drawback. These FGF21 super-mice developed weak
bones. Bone loss in these animals "may
limit its utility as a therapeutic agent" the researchers
So what is
the take-home message of this discovery? What can modern longevity-seeking
humans do to activate FGF21?
- One life-prolonging
practice might be to periodically fast. A 12-hour fast activates
FGF21 which then begins to increase fat burning. There are some
people who never eat breakfast, to prolong their daily fasting
period. While most dieticians say skipping breakfast leads to
overeating and obesity, almost all of the studies on this topic
have been performed among growing children. Children are growing,
not aging, and certainly donít fit into the category of middle-agers
who are experiencing mid-body weight gain.
A study of
over 5800 men reveals that breakfast
skipping modestly contributes to weight gain. A small study
a week fasting among adult males reduces weight.
approach might be to limit phosphorus in the diet. That is because
the aforementioned klotho protein limits excessive over-calcification
and phosphorus in the human body.
the relevance of phosphorus limitation to aging an understanding
of the klotho gene is required.
There is evidence
that adults who have lower
levels of klotho protein in their blood circulation have an increased
risk of death. Since FGF21 requires klotho protein to work,
investigation into mechanisms of klotho formation may be advantageous.
Mice that are bred to produce more
klotho protein live about 17.4% longer, not quite as striking
as FGF21 itself, but still would add more than a decade to humans
if animal research has application in humans.
how klotho works, researchers reveal that dietary
phosphate restriction reverses aging in laboratory mice bred
to not produce klotho protein. There is genetic and dietary evidence
that phosphate toxicity accelerates aging. When mice are bred so
as not to produce klotho protein and fed
a high phosphate diet, signs of premature aging appear.
in Japan are concerned about increasing
amounts of dietary phosphorus which may accelerate aging. Restriction
of phosphorus and calcium is advised. House flies (Drosophila melanogaster),
used in longevity experiments, age
prematurely when provided with a high phosphorus diet.
bar charts provided below. They provide convincing evidence that
diets high in phosphorus have deleterious effects upon human health.
Tonelli M, et al: Relation between serum phosphate level and cardiovascular
event rate in people with coronary disease. Circulation 2005;
Reproduced with the permission of Wolters Kluwer Health
Many fast foods
have phosphate additives. Excessive
phosphorus should be considered a health risk. Researchers suggest
no more than 1000 milligrams of phosphorus per day.
One of the
confusing aspects of understanding phosphorus in the diet is that
plant foods provide a natural calcium and phosphorus balancing
agent called phytate (inositol hexaphosphate or IP6) provided in
plant foods which inhibits the digestion of these minerals significantly
(from ~80% to ~20%0. It is the inorganic
phosphorus in food additives, prevalent in fast foods, that
is the culprit here. Supplemental IP6 is available as an extract
from rice bran and should be considered a powerful
anti-aging substance via its ability to calcifications and phosphorus
in Japan report on a novel way to increase FGF21 hormone via inhalation
of hydrogen gas or consumption
of hydrogen-fortified drinking water. Mice given hydrogen water
lost excessive weight experienced a decline in blood sugar, insulin
and triglycerides, all which was correlated with an increase in
FGF21. For the really serious pursuers of longevity, on the commercial
side there is even a hydrogen
drinking water produced in Malaysia that is touted for its health
benefits (though no evidence is provided this beverage has any health
to increase FGF21 would be to take the anti-diabetic drug metformin
which stimulates FGF21 in human liver cells (requires a doctorís
prescription). Physical exercise
has also been shown to increase FGF21 in young women.
him mail] is a frequent writer on health and political
topics. His health writings can be found at www.naturalhealthlibrarian.com.
latest book is Downsizing
© 2012 Bill Sardi Word of Knowledge Agency, San Dimas, California.
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