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The amount of insulin within the body determines
the amount of fat-maker message. Hormones, like insulin, carry information
to the body cells. Hormone information always concerns how cells
direct energy expenditure. Insulin carries information that tells
the cells to store energy. Most body energy storage occurs as fat.
Cholesterol is one type of body fat. The enzyme in the liver that
makes sugar into cholesterol turns up its activity when insulin
levels rise. Insulin levels rise following carbohydrate meals or
excess mental stress (among several other promoters). Rather than
tell doctors and the public about this simple causal relationship,
the media bombard us with the wonders of the statin drugs.
Statin drugs work, in part, because they poison this liver enzyme's
ability to listen to the insulin message. The trouble with poisons
concerns their inevitable side effects and toxicities. One nasty
side effect from these medications involves the depletion of coenzyme
Q10 in the body. The heart needs the lion's share of this important
nutrient. Deficiency here causes one type of heart failure.
Another emerging understanding for how statin drugs lower heart
disease risk involves their ability to subdue inflammation. Rather
than come clean and educate physicians about the most likely mechanism
for how this occurs, the statin-selling companies perpetrate the
story that it remains largely a mystery. The argument for its being
a mystery diminishes once a few critical clues enters into the discussion.
The first clue involves the long-known association between heart
disease and the Type A personality. Type A individuals are classically
described as hard driving, overachieving, and always worried about
their next deal. Physiologically, these emotions, when chronically
expressed, lead to a constant stress hormone response. The stress
response was designed to survive physical stressors. In order to
survive a physical stress, the massive dumping of fuel into the
bloodstream makes sense because exercising muscles consume the fuel.
Additionally, physical stressors often lead to trauma. This explains
why the acute-phase reactants predictably elevate with the onset
of the stressor. The acute-phase reactants prove appropriate with
trauma, but deleterious with mental stress. C-reactive protein (CRP)
is only one acute-phase reactant. Others include complement, interferon,
fibrinogen, ferritin, ceruloplasmin, and amyloid. Fibrinogen directly
increases the clotting tendencies of blood. Ferritin elevations
increase iron absorption into the body tissues.
With mental stress, once iron absorbs into the body, it proves very
difficult to remove. This detail may help explain the emerging realization
that many heart-disease patients have elevated ferritin levels.
It further explains a potential reason that chelation therapy maintains
its devotees, despite the ongoing criticism. Specifically, EDTA
binds and removes iron from the body. This fact may prove the number
one benefit for this approach.
Lastly, the acute-phase reactants' elevation in the setting of mental
stressors involves their inappropriate effect toward an increase
in angiogenesis propensity. The angiogenesis propensity increases
when the acute-phase reactants elevate. This again makes sense with
physical stressors because these traumas associate with the need
for new blood vessel formation.
Chronic mental stress promotes two powerful processes that promote
the angiogenesis critical to tumor growth: increased insulin needs
and the heightened angiogenesis propensity described above. These
facts, taken together, provide a likely mechanism for why overweight
and stressed individuals suffer increased morbidity and mortality
The second clue involves the emerging research results documenting
that the statin drugs lower CRP levels. Once one recalls the connection
between HMG-CoA reductase activity and steroid synthesis rates,
a more holistic picture emerges. Anything that subdues the adrenal
glands' ability to make steroids will also diminish the magnitude
of cortisol released for a given stressor. In turn, less cortisol
release subdues the acute-phase reactants' release. CRP is only
one of the acute-phase reactants. The normalization of acute-phase
reactants, in the chronic mentally stressed state, leads to less
inflammation for the reasons described above.
These facts initially sound "too good to be true." This
adage proves accurate, because the downside to this scenario provides
insight into the advantages of counseling Type A personalities about
the bigger picture of causal relationships.
To better appreciate the downside of the statins, one needs to recall
the typical body habitus of Type A personalities. The majority are
large in the waistline or at the very least have increased visceral
fat. Currently, a waist measurement above 40 inches is thought to
predict these metabolic syndrome types at risk for accelerated aging
and blood vessel disease. Over 50 years ago, obese individuals were
found to have increased stress steroid metabolites in their urine.
Uniting these two facts, it becomes easier to understand one of
the metabolic syndrome individual's driving pathological forces:
exaggerated stress steroid release rate for a given stressor. Another
way to look at this is, in the setting of chronic mental stress,
those prehistorically equipped survival machines selected for through
the ages have become the metabolic syndrome victims from chronic
sedentary-type stressors. What was once a survival benefit derived
from mounting a strong fuel release and acute-phase reactant release
(both secondary to a strong cortisol release) in the setting of
physical stress, has now become a curse, promoting excessive body
fat accumulation and blood vessel inflammation.
Excessive cortisol release violently activates protein dismantling
into more sugar (gluconeogenesis). Protein content within denotes
the metabolically active constituent of body tissue. Defense of
body protein content proves fundamental to healthful longevity.
Healthy people have sufficient growth hormone release that protects
their protein from excessive catabolism during these times. However,
middle-aged individuals who chronically experience stress but have
sedentary lifestyles begin to suffer various amounts of glandular
One mechanism for glandular decline involves the inappropriate elevation
of blood sugar caused by mental stress in the sedentary state. Elevated
blood sugar suppresses growth hormone release. Less growth hormone
release leads to less defense of body protein ability. This fact
ties in the observation about syndrome X patients evidencing sarcopenia.
It also elucidates the likely association between this syndrome,
and its underlying a variant presentation of Cushing's disease pathology
(see testing below).
With mental stress, the increased blood fuel has nowhere to go.
Hence, increased insulin amounts eventually release to normalize
the blood sugar. Again, this same metabolic derangement operates
within the classical Cushing's disease patient. Unfortunately, very
few physicians appreciate the sequential release of first cortisol
(catabolic) followed by increased need for insulin to correct the
inappropriate rise in blood sugar. It is the increased insulin that
make typical Cushing's disease patients fat. It is the increased
cortisol that causes excessive catabolism of their body protein
and chronic surges in their blood sugar levels.
Unfortunately, insulin releases into the portal vein and heads straight
for the liver. HMG-CoA reductase turns on with increasing insulin
and off with increasing glucagon. What was once protein a few minutes
before now is floating within the bloodstream as sugar. A few minutes
later, the protein turned into sugar is changed into cholesterol
and fat. Because the liver (and also fat) cells have 200,000 pure
insulin-type receptors per cell, insulin excess profoundly influences
the cholesterol profile.
A cognizance of this anatomical reality helps one to see that the
liver functions as an insulin trap, and only excessive amounts of
insulin secretion can spill past the liver and out into the general
circulation. Healthy people need less insulin because their livers
secrete sufficient IGF-1 that largely negates the need for insulin
between meals, while fasting, or when exercising. Circulating IGF-1
levels directly depend on sufficient growth hormone release. Realize
that only sufficient growth hormone release defends body protein
between meals, while exercising, or when fasting. All other counterregulatory
hormones (cortisol, epinephrine, and glucagon) make protein dismantling
for fuel creation fair game.
The old name for IGF-1 clarifies its crucial role in sugar metabolism,
the nonsuppressible insulinlike activity of the bloodstream. Many
physicians remain unaware of this fact, and this author finds it
rather odd that it fails to receive even cursory mention in discussions
of syndrome X pathology. The healthiest people possess the highest
IGF-1 levels. A falling IGF-1 leads to increased insulin need (insulin
The very survival of the statin drug-selling's rosy picture depends
on eviscerating certain scientific consequences that result from
a diminished glandular ability. When healthy, the adrenal glands
make both catabolic and anabolic message content. A higher anabolic
message content leads to a faster repair rate. The lower the antioxidants,
the more repairs need to occur. Here lies the additional risk of
chronically consuming statin drugs in place of healing lifestyles:
They contribute to the lack of repair from ongoing wear and tear
that the blood vessels encounter. Disrepair causes inflammatory
damage despite their benefit from inducing decreased cholesterol
and acute-phase reactant levels.
HMG-CoA reductase occurs within the adrenals and gonads. Any drug
or toxin that inhibits the steroid manufacturability within the
adrenals or gonads will also decrease the repair rate that logically
follows from diminished anabolic message content. Here lies another
downside that remains ignored until one begins to examine the interrelatedness
of steroid synthesis rates and HMG-CoA reductase activity.
In one way or another, blood vessel disease results from the repair
rate not keeping up with the injury rate. Statin drugs may in fact
lower the injury rate by diminishing the acute-phase reactants'
caused inflammation and cortisol-related blood sugar spikes. The
lessened blood sugar spikes lead to decreased insulin need despite
a sedentary and stress-filled lifestyle. A subdued stress response
means that less acute-phase reactants release, as well. However,
what is not being said concerns their probable negative influence
on the repair rate of blood vessels and muscle tissue. The repair
rate of muscles and blood vessels depend on androgen levels, like
all other DNA-containing body cells. Since science has already documented
subdued acute-phase reactants with statin usage, it remains quite
likely that other steroids' synthesis rates decrease, as well
The likely consequence of diminished testosterone, which results
from statin drug use, may help further elucidate the ongoing suspicion
about their contribution to heart failure. Many in the holistic
community attribute this tendency to the diminished coenzyme Q10
levels that logically follow. However, maybe a fall-off in testosterone
in some chronic statin users contributes to their pump failure as
Following serial 24-hour urine measurements for steroids would provide
a logical next step for testing the severity of diminished anabolic
message content. It will also further elucidate the before-and-after
profiles of the stress steroid metabolites of syndrome X patients.
Recall that, over 50 years ago, obese patients were documented to
have elevations in their 24-hour urine test for stress steroid metabolites.
If each doctor in the holistic community began collecting baseline
24-hour urine specimens for steroids, and followed them serially,
a new level of understanding would emerge about the association
of a heightened stress response, increased insulin need, and elevated
acute-phase reactants in the development of blood vessel disease.
At the very least, real hormone replacement therapy could be instituted
to address these steroid defects before they weaken the statin drug
user. Ideally, these types of tests could be used to help better
motivate the type A personality–derived syndrome X individual
take a more active role in which hormones secrete.
Most Cited References
on Statins' Effect on Testosterone Levels.
1. Azzarito C, Boiardi L, Vergoni W, Zini M, Portioli I. Testicular
function in hypercholesterolemic male patients during prolonged
simvastatin treatment. Horm Metab Res.
2. Bairey Merz CN, Olson MB, Johnson BD, et al.; Women's Ischemia
Syndrome Evaluation. Cholesterol-lowering medication, cholesterol
level, and reproductive hormones in women: the Women's Ischemia
Syndrome Evaluation (WISE). Am J Med.
2002 Dec 15;113(9):723–727.
3. Bernini GP, Brogi G, Argenio GF, Moretti A, Salvetti A. Effects
of long-term pravastatin treatment on spermatogenesis and on adrenal
and testicular steroidogenesis in male hypercholesterolemic patients.
J Endocrinol Invest. 1998 May;21(5):310–317.
4. Bohm M, Herrmann W, Wassmann S, Laufs U, Nickenig G. Does statin
therapy influence steroid hormone synthesis? Z
Kardiol. 2004 Jan;93(1):43–48.
5. Dobs AS, Miller S, Neri G, et al. Effects of simvastatin and
pravastatin on gonadal function in male hypercholesterolemic patients.
Metabolism. 2000 Jan;49(1):115–121.
6. Dobs AS, Sarma PS, Schteingart D. Long-term endocrine function
in hypercholesterolemic patients treated with pravastatin, a new
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Metabolism.
7. Dobs AS, Schrott H, Davidson MH, et al. Effects of high-dose
simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia.
Metabolism. 2000 Sep;49(9):1234–1238.
8. Hyyppa MT, Kronholm E, Virtanen A, Leino A, Jula A. Does simvastatin
affect mood and steroid hormone levels in hypercholesterolemic men?
A randomized double-blind trial. Psychoneuroendocrinology.
9. Ormiston T, Wolkowitz OM, Reus VI, Johnson R, Manfredi F. Hormonal
changes with cholesterol reduction: a double-blind pilot study.
J Clin Pharm Ther. 2004 Feb;29(1):71–73.
10. Santini SA, Carrozza C, Lulli P, Zuppi C, CarloTonolo G, Musumeci
S. Atorvastatin treatment does not affect gonadal and adrenal hormones
in type 2 diabetes patients with mild to moderate hypercholesterolemia.
J Atheroscler Thromb. 2003;10(3):160–164.
In general, at first glance, these articles effectively cause the
inquiring physician to lose enthusiasm about a negative consequence
between statin usage and steroid levels. However, four main points
(beyond the numerous methodological flaws that occurred with most
of these individual studies) allow the revival of integrative physicians
collaborating further and providing less dubious conclusions: (1)
All the above studies fail to differentiate between high cholesterol
and the presence or absence of heart disease in their cohort groups;
(2) 8 out of 10 of the above studies are of 24 weeks' or less duration;
(3) the 2 studies that most convincingly demonstrate the diminution
of steroids with statin drug use were the only studies longer than
24 weeks' duration; (4) none of the above popularly cited studies
utilized the gold standard of scientifically assessing steroid status
– the GC mass spec derived values from 24-urine results. Only
GC mass spec measures the important steroid metabolites that add
Possibly, for these reasons, the time is ripe for holistic physicians
to spend less time initially persuading their patients against statin
therapy and, for a short while, begin documenting the effects of
such therapy by monitoring the 24-urine steroid profiles before
and after treatment in their patients that prefer the pill approach.
Meridian Valley Labs and possibly Rhine Labs will be all too happy
to begin to collect and organize this data. Preliminary findings
of those patients on statin drugs with heart disease tend to support
a negative correlation. This will prove helpful if there is truth
in the long-held suspicion that those individuals with lower testosterone
to start with are the very ones that are at increased risk of atherosclerosis.
Therefore, lowering cholesterol without maintaining testosterone
will prove to be folly.
William Ferril, MD
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