On the Science of Essential Nutrients
By John T.A. Ely
Copyright 2002
Overview
"Unprofitable" modalities (UM) refer to published scientifically proven
treatments ignored by mainstream medicine as unpatentable and unprofitable.
Commonly, o optimize health, UM simply adjust certain molecules normally in the
body to significantly different levels than typical in affluent societies. For
recovery of health, the changes can be much larger. Some molecules such as
sugar, tryptophan and methionine must be kept below specifiable levels.
Misunderstood essential nutrients including coenzyme Q10 (Q10) also called
ubiquinone, ascorbic acid (AA), and vitamins A and E (A, E) must be
supplemented, in some conditions, to many times the RDA's. Such changes are
called orthomolecular (i.e., correct molecular levels for homeostasis). They are
pure science, not quackery as supposed by those, unread, who condemn without
investigation.
A world-famous physician from Stanford University made a
generalization re orthomolecular "megadosing". The last sentence from Cathcart
(1981) states: "I anticipate that other essential nutrients will be found being
utilized at unsuspectedly rapid rates in disease states. Complications caused by
failures in systems dependent upon those nutrients will be found. The magnitude
of supplementations necessary to avert those complications will seem
extraordinary by standards accepted today."
Mainstream medicine (of
which the authors are constructively motivated but dissenting members) has
recently received strong criticism cited here from the most respected
authorities (Pauling, Relman, Shute, Watson, etc.) which we, sadly, cannot
refute. Medicine has been accused of being both the sole judge of its own
quality and historically calloused in its slowness to modernize (by elimination
of long held erroneous views) at enormous cost in morbidity and mortality
(M&M) (Ely, 1999). Today there are still erroneous ideas that cripple
medicine in the US and other countries with similar medical systems. These were
shown in reveleations by Pauling (1987,p.234; Ch.25; etc.) and Shute
(1975,pp.230-242), to have resulted from deliberate deceit on the part of a few.
The ensuing rejection of UM, even essential nutrients (usable alone or
adjunctive to conventional therapy), has been perpetuated by their low cost and
unpatentable nature. This, even though they are less invasive, have less side
effects and yield a much longer and higher quality of life. The related change
of US medicine from social service to a profit driven exploitation of captive
ignorant customers was criticized and lamented by Harvard Medical School
professor and former Editor-in-Chief of New England Journal of Medicine, Arnold
Relman (1992). Unfortunately, a small number of the UM are essential nutrients
without which a human cannot have a long or healthy life, let alone have
successful surgery, resist disease, or retain youthful tissue. Nor can one avoid
continuous subjection to the outmoded ineffective high cost "treatments of
choice" (ToC) that accelerate death. Rejection of these UM causes the exorbitant
ToC to cost US annually over 1 million early patient deaths (before age 65) and
over US$1 trillion (> 1/6 of the national debt). From infections alone, there
are ~200,000 US deaths annually, costing ~US$18 billion. Addressing the Mayo
Clinic, T. J. Watson, CEO of IBM, (1973) said the US spends more of its GNP for
medical care than any country on earth but is 24th in life expectancy
(males)..."and becoming as a nation a massive medical disgrace." These failures
of ToC occur primarily because the rejected UM include the essential nutrients
without which no treatment, pharmaceutical or otherwise, can succeed. The
failures dominate every specialty, cardiology, oncology, etc, and, surprisingly,
immunology most of all, as we show below (see "Immunology's Failure").
Rejected methods of great value lie buried and unused in the many
millions of pages of recognized medical science research and clinical literature
(medlit) published over the past 50 years (currently over 40 million pages per
decade). How can it be that countless unused therapies, better than ToC, abound
in medlit? There are several factors contributing to these problems. First,
society's expectations of clinicians are not humanly possible to fulfill. In
addition to the literature size problem, there are: constraints imposed by
medical disciplinary boards that forbid departing from ToC; clinical journals
gain support from ads of, and are strongly influenced by the pharmaceutical
industry; education of physicians in use of pharmaceuticals (which necessarily
cost enormous sums to develop) must be actively implemented by the detail
persons of the drug industry; etc. It is no wonder that UM lie unread.
Medical Literature (MedLit) Plan
The MedLit Plan is
advanced to improve the quality of medical care simultaneous with major
reductions in its cost. This requires the addition of long known but ignored UM
that can end and reverse five decades of falling efficacy and increasing cost of
ToC. Before discussing specific examples of the UM, we list some of the related
areas of ignorance (especially re essential nutrients) in mainstream medicine so
fundamental it seems preposterous to think they could exist. These include: (1)
Q10 whose structure and functions have been known for ~40 years, while the
absolute necessity of supplementing Q10 in the aged and ill is ignored by
mainstream physicians, most of whom had never heard of it in 1999; (2) the
pharmacokinetics of AA in mammals; (3) totally inadequate AA body pools accepted
as normal in humans (i.e., non-synthesizing mammals); (4) the profound effects
of AA deficiency in disease, other stress, and aging; (5) the striking success
reported since 1949 of correcting this deficiency in infections and other
disorders; (6) the effects of glycemic (blood glucose, BG) modulation on cell
mediated immunity (cmi), cancer, etc (some known for over a century); (7) the
hyperglycemic levels accepted as normal in affluent populations; and (8) other
essential nutrients, such as A and E, also important for all degenerative and
infectious diseases.
Coenzyme Q10. (see also
http://faculty.washington.edu/ely) Q10 has been listed for years as an essential
nutrient in the Physicians Desk Reference (PDR) (e.g., 1988, 42nd Edition,
p.2154). Normal healthy humans have a Q10 average blood level of ~1ppm
(1mcg/ml), but obtain only a very small fraction of their Q10 from food. Most
(~0.5g/d) is synthesized in all tissues (body pool ~2g), including the liver, by
a complex process requiring many nutrients as substrate (Langsjoen, 1995; PDR
1997, p.2769). In the ill or infirm, Q10 is usually <1ppm; a typical daily
oral dose is 400 mg which should raise blood levels to 2 to 4 ppm (some people
absorb poorly, requiring more). To get 400 mg Q10 from two of the best food
sources would require eating ~20 kg peanut butter or ~5 kg of mackerel.
Synthesis decreases after age 20 and may fall off rapidly after middle age,
accelerating aging itself. Q10 is needed by every cell (and system) in the body
for: (1) synthesis of adenosine triphosphate (ATP, molecules for energy); (2)
cell membrane fluidity; and (3) protection against free radicals (50 times more
antioxidant power than E, but E is still needed for other reasons). Exercise
increases catabolism of and need for Q10. In disease or other stress, intake and
absorption of the substrate (component) molecules is impaired. This reduces Q10
synthesis, causing further degradation of function due to a Q10 deficiency state
in one or more (possibly all) systems in the body. Q10 supplementation is
beneficial in the prevention, treatment or cure of heart disease, stroke,
cancer, viral diseases including AIDS, etc. Q10 slowed aging markedly, restored
youthful thymic response to viruses and tumors, and extended lifespan 50% when
given to very old mice (Bliznakov, 1973). Safety and efficacy of Q10 has been
demonstrated in numerous very large clinical trials (Langsjoen 1995; Langsjoen
and Langsjoen 1999; Ely and Krone 2000). A caveat: in patients with alkalinized
stomachs, oral Candida can colonize upper gut (potentially lethal) and candidal
growth can be stimulated by Q10 (Krone et al 2001). Before prescribing Q10,
their physicians should study Marshall et al (1988).
Aging mutations
occur at a very high rate in mitochondria (compared to intranuclear DNA which
are stabilized by histones) if ubiquinone, AA, etc are low. In this aging
mechanism, low values of ubiquinone permit oxidative damage to the DNA of
mitochondria to accumulate, permanently and progressively impairing their
ability to function. If, by supplementation, the ubiquinone level is restored to
its proper value, the rate of oxidative damage will be lessened, but the
impairment remains. Because of its free radical dependence (in contrast to
glycation), this process gives increased emphasis to the importance of the
theory of aging proposed by Denham Harman in the 1960's (1969; 1981; 2001).
Actually, Harman first integrated the theoretical and experimental work by
himself and others to predict in 1972 that mitochondrial aging is a principal
cause of early death (1972)].
Ascorbic Acid has many functions.
Over 20,000 papers on ascorbic acid (AA) published in indexed journals since
1964 are accessible on Pub Med. Many others, including some with most important
findings were published earlier, >1200 in 1938-1939 alone. It is commonly
called vitamin C although it is not a vitamin The short treatment of AA
pharmacokinetics offered here is believed simpler and more physiologically
correct on basic concepts than any published before. Lack of this understanding
has been pivotal in the clinical failures of modern medicine.
All
mammals have the same requirements for AA. Among mammals, only humans, the
other primates, the guinea pig and a fruit eating bat are known to have lost (by
genetic defect) the ability to synthesize AA. It is most important to appreciate
that other features of AA kinetics were not lost. The same high needs exist in
these four non-synthesizers that constitute an abnormal group. It is observed
that many and possibly all ~4000 other mammals are normal and synthesize AA
copiously from glucose in the liver. This is necessary because AA has numerous
functions necessary for optimum health requiring its presence continuously at
high concentrations throughout the body. These functions and the associated high
serum levels, far above the AA renal threshold, ~1.4mg/dL (mg/deciliter,
commonly read "mg per centum" and written mg%), are the same in the 4000 normal
and the four abnormal mammals. Thus, both groups of mammals have approximately
the same daily AA requirements, ~50mg/(kg body weight), to replace urinary and
catabolic losses when young, healthy and unstressed. It is possible, with care,
to obtain this amount from food (Pauling, 1987,p.99).
Consequences of
non-synthesis. In the stress of pain, disease, intoxication, etc., normal
mammals respond by increasing AA synthesis in an intensity-dependent way up to
several hundred fold, excreting AA "far in excess" of total body stores each day
(Lewin, 1976, p.109). Because such amounts of AA could not be obtained from
food, even if it could be consumed, it is clear why most mammals still
synthesize AA. When a human suffers injury, surgery, intoxication, infection,
etc, the AA pool is also rapidly distributed to the sites of use. However, it is
depleted with dire consequences because a large concurrent AA synthesis by the
liver, for which the rest of the body is still programmed, does not occur. This
dangerous fall of AA to scorbutic levels within 12 hours after stress was
reported in 31 consecutive heart attack patients (Hume et al, 1982). In such
situations, an enlightened physician provides the AA a normal 70kg mammal would
have synthesized, perhaps 70g/d or more, saving the patient.
Treating
with AA can be simple. For numerous clinical applications, AA dosing is
simple, i.e., 10g/d indefinitely (e.g., see chronic hepatitis below). A second
example: in a 1976 study, human lymphocyte multiplication rate ~doubled if the
donors had taken AA 5g/d for 3 days, tripled after 10g/d, and quadrupled after
18g/d (Pauling, 1987,p.132).
Treating with AA can be complex.
There are a number of complications that must be understood for many other
disorders. As detailed in Glycemic Control below: (1) when BG is low,
intracellular AA becomes high and the hexose monophosphate shunt (HMP) is
strongly stimulated because it runs at a rate proportional to intracellular AA
(Cooper et al, 1971); and (2) lymphocytes multiply more rapidly and phagocytes
ingest and kill more effectively when intracellular AA is high. A classic
example of this effect of AA on lymphocyte multiplication is the 1976 study
above. Such human white blood cell (wbc) AA systematics are quantified and
explained by study of Cooper et al (1971), Denson et al (1961), and Figure 7.2
(Lewin, 1976). Although awkward, correct AA dosing (humanity's only choice)
yields impressive medical benefits. However, dosing obviously pales in
comparison to the instantaneous effortless response of the AA synthesizer to
infectious challenge.
Immunology's failure. The discovery that
HMP rate is proportional to intracellular AA should have changed all fields of
medicine. Because Cooper et al (1971) used wbc, all immunologists should have
immediately changed their thinking on AA. Certainly, some of them read
"Infection and Immunity". Even Ely, who is not an immunologist by training, was
able to extend the theory and obtain new findings in aging, birth defects,
cancer, infectious diseases, etc (some cited here). In 1971, immunologists
should have realized explicitly that intracellular AA (as measured by buffy coat
(wbc) AA): (1) gives a prompt indication of immune status: and (2) is a
universal limiting factor that determines the rate and intensity of cmi response
in humans. Yet, nearly 30 years later, in a recent study of six excellent and
highly respected immunology texts (Fudenberg, Roitt, Klein, etc) published from
1980 to 1998, none mentioned the HMP-AA need. Ely felt that even his coauthor
(Ely et al 1998, 1999; Krone et al, 2001), H. H. Fudenberg, the 4th most
frequently cited immunologist in the world for 15 years, had taken part in this
oversight, although his book was the only one that mentioned the HMP at all and
also reviewed transfer factor. In recent telecons with two of the most famous
immunology authors, one a Medicine Nobel Laureate, both agreed these serious
omissions must be corrected. Texts in other specialties are equally remiss.
Aging and death. Optimum health certainly includes the
maintenance of youthful properties in structural proteins. One of the largest
parts of the 50mg/kg AA required for all unstressed mammals is in the
hydroxylation reactions necessary to constantly renew the flexible quality of
collagen and the elasticity of elastin (blood vessels, lungs, etc.) degraded by
"daily wear and tear" (Pauling, 1987,p.92). If the AA intake is the low level
necessary to prevent scurvy, the human may avoid scurvy but will not be able to
renew structural proteins and will age more rapidly. In a follow-up study of 577
people over age 50 in California, low AA intake predisposed to high mortality.
The death rate was more strongly correlated with AA than any other variable
including tobacco (Pauling, 1987,p.107).
Disease Prevention and
Treatment. The best AA synthesizers are resistant to most viral diseases,
tuberculosis (TB), diphtheria, and also do not share the susceptibility to
anaphylactic shock, leukemia, and polio-like infection seen in the human and
guinea pig. With normal BG and high AA blood levels, humans and guinea pigs also
become resistant to these disorders, and, like the normal mammals, spill AA in
the urine (dog ~1g/d) as a small price for this protection. The antibiotic
properties of AA act directly by bacteriostatic and bactericidal levels in body
fluids and indirectly by stimulating wbc.
Fred R. Klenner, MD, Duke
1936, originally a chemist, had many important discoveries in medicine that
should be read by everyone (e.g., Klenner, 1949, 1971, 1974). In patients,
dosing with amounts that elevate wbc AA sufficiently (50-100 g/d by iv and/or
oral)* produces prompt (3-7 day) cures of polio, viral encephalitis, acute
hepatitis (all types), etc. A simple dosing method, called "titration to bowel
tolerance" (TBT), permits a very sick outpatient to administer AA in exactly the
correct oral dose each day (flu, mono, etc) is explained by Cathcart
(1980,1981).
* In iv dosing, AA is always sodium ascorbate.
Miscellaneous, Primarily Bacterial. Bacterial infections were
studied in the 1930's and 1940's by researchers who published hundreds of papers
but used inadequate doses because of their conviction that AA was a vitamin.
However, their findings were sufficiently encouraging that it appeared almost
certain that the "massive" doses used by Klenner and Cathcart would cure the
following infections (some rapidly): diphtheria, dysentery, leprosy, pertussis,
pneumonia, TB, typhoid fever, typhus (and other rickettsial diseases). These
papers were reviewed by Irwin Stone (1972) who introduced Pauling to AA. Klenner
reported serious bacterial infections including diphtheria, hemolytic strep and
staph clear within hours following one injection of AA, as sodium ascorbate of
course, 0.5 to 0.7 g/kg body weight and "run in through a 20G needle as fast as
the patient's cardiovascular system will allow" (1974,p.49). And, he reported
(1974,p.62) that "massive daily doses will also cure tuberculosis..." but we
have been unable to find how massive (50, 100 g/d?) or for how long (months,
year?); this may not be difficult to determine in NZ, using "bowel tolerance."
It has been demonstrated by Sirsi (1952) that a bactericidal level in vitro and
in body fluids for virulent Mycobacterium tuberculosis is 10 mg%. Humans with
sufficient AA intake to maintain the bacteriostatic level for TB (only 1 mg%) do
not develop TB. In a 5-year follow-up study of 1100 men originally free of TB,
28 cases developed, all in the group with substandard blood AA levels (Stone,
1972,p.81). Cathcart (1981) has reported that serious uncontrollable infections
by antibiotic resistant bacteria (necrotizing fasciitis, etc) can be
successfully treated in a week with megadose AA along with the antibiotic,
ineffective alone. The necessity of high AA in wbc for cmi has been stressed
above.
Miscellaneous, Primarily Viral. In diseases requiring
prolonged treatment [i.e., acute hepatitis (week), viral encephalitis (days)] a
variety of protocols exist; AA is often given around the clock with intravenous
ascorbate (ivc) drip and always with oral. Vitamin E should be given with AA to
everyone, preventing hemolysis in Northern Europeans and others except people
with genetic lytic tendencies. These should have medical supervision,
erythrocyte testing, E, and due caution for multigram AA dosing. Because of
total ignorance re AA in mainstream medicine, no one has tried it against the
most frightening viruses (hanta, Ebola, etc). Theoretically, it should cure them
just as well as polio, except for any that produce latency, and might control
most of these. Although it has been reported by Cathcart (1984) that AIDS
patients could be stabilized by high level AA („10g/d), no one expects this
modality can cure HIV. This has only been done with antigen-specific Transfer
Factor, another unprofitable modality.
Prognostic value of the ratio
AA/DHA. In optimum health, the ratio exceeds 10. In the sick and moribund,
AA/DHA drops below 1. This reverses the redox potential, removing reducing power
just when it is needed most, accelerating the ratio's fall and death. In 163
patients studied, Chakrabarti and Bannerjee (1955) found this ratio is
prognostic even when the impending death is from a highly lethal disease. Thus,
raising AA/DHA above 10, preferably by iv (or intubation) should save the lives
and cure the diseases as is reported by Klenner and Cathcart.
Much
additional information will be given in Apresi Bulletins and can be found in
Cathcart (1980, 1981, 1984) and Klenner (1949, 1971, 1974) most of which are now
available on Cathcart's website (www.orthomed.com).
Glycemic
Control. Almost 2000 years ago in the time of Galen, it was observed that
tumors grew poorly or not at all in underfed (i.e., low BG) animals. In 1972,
Ely deduced and related to Linus Pauling a theoretical reason why clinical
trials of AA against colds and cancer might fail because of the high BG levels
in the affluent nations. The theory is relevant to aging, birth defects, cancer,
cardiovascular disease (cvd), infections, etc. It is called the "Glucose
Ascorbate Antagonism" (GAA) and is important in the "small" dose range (AA~10g/d
or less). It says that certain cell types such as leukocyte and fetal have
intracellular AA levels that are "pumped up" largely by insulin ~50 times higher
than serum AA levels in the surrounding blood. This occurs if BG is in the low
range that was normal until the 1900's and is still seen today where the
primitive (unrefined) diet prevails, i.e., 50-90 mg% two hours postprandial (Ely
1996; Chatterjee and Bannerjee, 1979, Table1). The high AA levels in such cells
are needed to drive the HMP shunt to supply hydrogen peroxide for phagocytosis
and ribose for mitosis. "Modest" BG elevations (~50%, common after western diet
meals) competitively inhibit insulin-mediated active transport of AA into these
cells, resulting in low intracellular AA levels, low HMP shunt, and cell
dysfunction (i.e., leukocytes don't attack tumors or pathogens, fetal cells
divide too slowly, etc.); this is the "Antagonism". It has been suggested that
low BG may also cause the removal of negatively charged sialic acid (a 9-carbon
sugar) from tumors that otherwise repel negatively charged T-cells. A principal
cause of cvd is hyperglycemia which reduces AA to scorbutic levels in vascular
intimal cells (see pp. 52-55 in Pauling 1987). The GAA theory gives rise
naturally to "Aggressive Glycemic Control" (AGC) as a modality that, properly
used, appears to have much value against many disorders as stated above.
Some Hypoglycemic Limits. Of course, one doesn't want BG too low
because cortisol rises and can damage cmi by its lympholytic effects. Also,
humans become unconscious (not necessarily harmful) below 40 mg%. Brain damage
is reported to occur below 20 mg%. However, cmi is reported to work well down to
ca 10 mg%. Cancer, infections and other diseases (cvd, etc) have much lower
incidence with adequate AA and BG 50-90 mg%. In insulin-coma therapy, formerly
used in the treatment of psychiatric patients, blood glucose was maintained
circa 30 mg%. Incidental to this, remissions from cancer were reported to occur
in patients whose incurable malignancies were unknown to the psychiatrist at the
time of treatment (Koroljow, 1962). A more practical AGC might maintain BG at
50-60 mg% with insulin or Orinase (a non-halogenated oral hypoglycemic).
Trivalent chromium deficiency in US soil and diet causes impaired glucose
tolerance, high BG, and disease (Ely, 1996).
Studies in Humans and
Animals. In 1978 and 1979, two inoperable stage-4 breast cancer patients
with large tumor burdens, worsening rapidly ("one month" prognoses) although
already on chemotherapy, elected to use AGC and both became tumor free in six
months and were still alive in 1992 (Ely, 1996). With partial support from Fred
Hutchinson Cancer Research Center (FHCRC), etc., Ely and co-workers were able to
reproduce this result in an animal model showing strong glycemic modulation of
tumor tolerance (Santisteban et al, 1985). In 1983, an American Cancer Society
UW-FHCRC committee (reviewing applications from new investigators) approved AGC
as a research topic and urged Ely to pursue it without delay. The obvious
theoretical relevance of GAA to birth defects had already been described (Ely,
1981). As explained above, hyperglycemia (high BG) slows cell division. Thus,
high BG in early pregnancy, causes gross malformations (about 60,000 per year in
the US!). But, high BG in late pregnancy, when cell division is primarily in the
brain, produces reduced brain mass and mental retardation, or other CNS defects.
The theory was cited in a lead article by a recognized expert in the field
(Cousins, 1983). Motivated by that review and need to test the GAA theory in a
non-tumor model, Ely et al showed that hyperglycemia of early pregnancy did
induce striking reproductive anomalies in an animal model [mainly fetal
resorption in mice (Hamel et al., 1986)].
Other Nutrients.
In
both health and disease, all essential nutrients must be adequate. It has long
been known that steroid excess, even endogenous cortisol elevation due to
stress, depletes vitamin A, depressing immunity. Antibodies cannot be produced
if vitamin B5 (pantothenic acid) is deficient. Some essential mineral
deficiencies (zinc, selenium, magnesium) suppress cmi. For the numerous benefits
of vitamin E as published in leading journals, from 1950 on, by world respected
clinicians (ie, Ochsner, Haeger, etc), and its arbitrary insulting rejection by
self-appointed "authorities", see revelations by Pauling (1987, p.210), Shute
(1975) and Cilento (1973). For example, inter alia, Ochsner found in surgery
that E is a safe prophylactic against venous thrombosis without producing a
hemorrhagic tendency. It is surprising that E, second only to Q10 among
available antioxidants, known for ~50 years could be termed "worthless" by a
prominent nutritionist (Shute, 1975, p.77). Although d-alpha tocopherol acetate
is a stable form of active E, other forms that are inactive and/or unstable have
caused much confusion for 60 years. It is well known that: (1) cholesterol is
not a risk factor for cvd unless LDL is oxidized; and (2) this is simply
prevented by E (Gey et al., 1991; Esterbauer et al., 1991). In the late 1940's,
the Shutes were able to show striking beneficial effects in cvd and other
patients by 300 IU E/d. They were also able to conclude that loss of E in food
processing to produce the US refined diet was a most probable cause of the
appearance and growth of cvd as the largest producer of M&M from ~1916 on.
These matters are known to capable students of nutrition. Until recent Q10
stroke findings (Ely et al 1998), Shute's E therapies were the only or best
available for cvd, rheumatic fever, stroke, etc.
Acknowledgements
We are grateful to Linus Pauling whose wisdom, courage and stature
gave weight to the arguments of those who understand the tragedy of US medicine,
identified those responsible, and collected in one volume over 450 references to
facilitate the eventual victory of science and truth (Pauling, 1987).
References
Back to
Science of Essential Nutrients
Updated September 2002