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 2002 Dr.

Dan
Daniel L Fouts
Over $ 1.3 trillion a year spent on
U.S. HEALTH CARE.
That is more per person than any country
in the world!
That 1.3 Trillion Dollars bought us

# 37
In the world in ability to achieve vital
health goals according to the World
Health Organization’s
World Health Report 2000
FOU R M AJOR
CHA LLE NGES IN
HEA LTH C ARE TOD AY
 Chronic degenerative
diseases -120+ million
Americans
 Autoimmune diseases -
50+ million Americans
 Infectious diseases -
multiple anti-biotic
resistant strains
CHILDR EN A RE DEVELOP ING
“A DULT ONS ET” DI SEASE S AT
A FRIGHTE NING RATE
 Hundreds of medical studies in the last
few years are looking at viruses and
bacteria as etiological factors in diabetes,
heart disease and heart attacks.

 Antibiotic resistant bacteria and rapidly


mutating viruses indicate that our only
reliable defense may be a strong immune
system.

 The incidence of cancer and autoimmune


diseases occurring in children is increasing.
• HMO’s and PPO’s try to tell us
how to treat and how much
they are willing to pay.
• Many patient’s have the
opinion that prescription
drugs can be: “too toxic,
too expensive and too
unreliable”.
• “50% of patients had or were using some form
of alternative medicine…” JAMA, July 2,
1997
• “…itis no longer possible to get all of the
nutrients necessary in our standard diet
to maintain optimal health.” JAMA, July 2, 1997
• “243million more visits to alternative providers
than all types of traditional primary
care physicians combined.” JAMA,
CONSIDER THIS
1998,(19)1548-1553 from the above JAMA
article:
An estimated $21.2 billion was spent on
alternative providers with an estimated $12.2
billion out of pocket AND the public is
spending more $ BILLIONS in cash on
MEDICAL
EDUCATION
• Presenthealthcaresystemis EVENT-FOCUSED:
HealthMaintenanceOrganizationsounds good- butinreality
is only anattemptatearlier detectionof diseasewhenitis
cheaper to treat. Wearegoodatprev entingdeath- not
ve
preservinghealth. After theevent, wedo somethingaboutit.
• Complementary medicineis morePATIENT-FOCUSED:
Meaning: DiseasePrevention, HealthPromotionandDisease-
Managementby usingthe“bestof bothworlds”- modern
MedicineandNutraceutical Technology.
• This results inimprovedpatientresponse, decreased expense and
increasedfinancial rewards for thehealthcareprofessional.
Thehealthcareprofessional faces TWOCHALLENGES in
incorporatingnutritioninto thedailypractice:

1. Greater degreeof Liability for recommendations - wemustbe


confidentof thescientific validationof Nutraceutical
products.
2. Thousands of products to choose- whichto use? Fewof us hav e
ve
thetimeor desirefor another “four years”of study to learnall
aboutnutrition. WhatcanweSTART usingsafely and
effectively intheofficeTOMORROW?
CARBO HYD RATE BAS ED
TH ERAPE UTI C
TEC HNO LOG Y
AN D

GLYCO NUTR IENT


TEC HNO LOG Y
THE CHANGING CARBOHYDRATE
PARADIGM:
FUEL SUPPLY VS STRUCTURAL
BUILDING BLOCKS
One of the newest and most exciting areas
of medical research
is in the area of Glycobiology - carbohydrate
technology.
Nutrition literature - carbohydrates are
fuel supply only.
fuel supply only.
Recent biochemistry - some special
“Super Carbs” are information rich
molecules that control a vast array of
Glycocompounds 98
Intertech’s Business Development Forum on Bioactive Carbohydrates
Glycocompounds 98 – the road to commercialization
November 2-4, 1998 – Renaissance Vancouver Hotel – Vancouver BC
 

Anti-Cancer, Anti-Infective,anti-Inflammatory, Anti-Biotic,


Anti-Viral
 

Get a comprehensive business and technical update from 22 leading


organizations as they map a path for successful glyco-drug
development – from discovery technologies and structure function
analysis through pre-clinical screening, clinical trials and approvals.
Along the way you’ll… receive the latest information on carbohydrate-
protein interactions and their impact on the development of a new
class of pharmaceutical compounds. Get updated on the biological
Advanced Bioresearch
functions Archer Daniels
of glycoconjugates andMidland Bayer AGLearn howBiosolutions
their receptors. to speed
Blanver/Zetapharm
up and capitalize Cantox
on drug discovery Cargill Inc.
by utlilizing advanced research andCH2M
Hill Chemstar Products Ciba Chomerica
production technologies. Get briefed on the commercial prospects and
Cytec Industries Dai-Ichi Kogo Seiyaku Dow Chemical Drug
current
Discovery applications
Dupont for carbohydrate-basedFMC Corp therapeutics. Genentech
Gist-Brocades Hercules Inc Hoffman-Laroche AG Johnson & Johnson
ICI Lonza Inc. KPMG Peat Marwick McNeil Labs
Maryland Biochemical Merck MIT
Metsa-Serla Chemicals Monsanto Life Sciences National Starch Proctor and
Gamble Phytogen Life Sciences Quest International Remy Industries
Rhone-Poulenc Roche Bioscience Ross Laboratories SafeScience Inc.
Searle Schwabe USFDA Stanford Univ.
University of California Zeneca Warner-Jenkinson
 
Glycoconj J 2000 Jul-Sep;17(7-9):553-65
 
Progress in deciphering the
information content of the 'glycome'--
a crescendo in the closing years of the
millennium.
Feizi T. The Glycosciences Laboratory, Imperial College School of Medicine,
Harrow, United Kingdom.

The closing years of the second millennium have been uplifting for
carbohydrate biology. Optimism that oligosaccharide sequences are bearers
of crucial biological information has been borne out by the constellation of
efforts of carbohydrate chemists, biochemists, immunochemists, and cell-
The direct involvement of specific
and molecular biologists.
oligosaccharide sequences in protein targeting and
folding, and in mechanisms of infection,
inflammation and immunity is now unquestioned.
With the emergence of families of proteins with carbohydrate-binding
activities, assignments of information content for defined oligosaccharide
Dr. Mondoa’s book
is helping to
change the old
biochemical
paradigm that
carbohydrates are
just a fuel supply
for the body. The
tremendous
potential of this
special group of
bioactive sugars
promises to change
AnnuRevBiochem 1976; 45:217-37
Comparativeaspects ofglycoproteinstructure.
Kornfeld R,KornfeldS.
Glycoproteinshaveawidedistributioninnatureandserveavastnumber of functions.
Thereareglycoproteinenzymes andhormones;glycoproteinsare foundinbloodand
secretions, in cell membranes, and in connective tissue. Of all the biologically
occurringmacromolecules theglycoproteins, which consistof carbohydratemoieties
convalently linked to a polypeptide backbone, represent themost diverse group,
rangingfromsubstances inwhichthecarbohydrate component represents less than
1% of the total weight to those in which It represents over 80% of thetotal. The
proteoglycans, which areclassified separately from otherglycoproteinsandinclude
thechondroitinsulfates,dermatansulfates, andheparinprimarilycarbohydrateinthe
form of numerous heteropolysaccharide chains attachedto apolypeptidechainat
closely spacedintervals. Thesugars thatcommonlyoccur inglycoproteins
include galactose, mannose, glucose, N-acetylglucosamine, N-acetyl-
galactosamine, sialicacids, fucose, and xylose. The proteoglycans also
containvariousuronicandsulfatedamino sugars.
• Structural molecules • Immunolgic
- cell walls
molecules -
immunoglobulins
- collagen, elastin
-
-
histocompatability antigens
fibrins
- bone • Enzymes
matrix
- proteases
• Lubricants and
protective agent - nucleases
-
-
glycosidases
mucins
- clotting
factors
- mucous secretions
• Cell attachment /
• Transport molecules recognition site
for - vitamins
Science 2001 Mar 23;291(5512):2370-6

Glycosylation and the immune


system.
Rudd PM, Elliott T, Cresswell P, Wilson IA, Dwek RA.
The Glycobiology Institute, Department of Biochemistry,
University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Almost all of the key molecules involved in the innate
and adaptive immune response are glycoproteins. In
the cellular immune system, specific glycoforms are
involved in the folding, quality control, and assembly
of peptide-loaded major histocompatibility complex
(MHC) antigens and the T cell receptor complex.
Although some glycopeptide antigens are presented by the MHC,
the generation of peptide antigens from glycoproteins may
require enzymatic removal of sugars before the protein can be
cleaved. Oligosaccharides attached to glycoproteins in the
junction between T cells and antigen-presenting cells help to
orient binding faces, provide protease protection, and restrict
nonspecific lateral protein-protein interactions. In the
humoral immune system, all of the immunoglobulins
SCIENTIFIC DISCOVERIES continue to reveal
new information about how our bodies
maintain health, prevent disease, fight
disease and how to slow the aging process.
NEW KNOWLEDGE - NOW WHAT ?

TWO OPTIONS to use the knowledge:

1. Try to develop a new drug that will


block, alter, stimulate or inhibit so that we
can “fix” the body or “cure” a problem.
2. Cooperate with what the body knows
how, and is trying to do by supplying it
with the raw material “tools” it is already
Recognizing the critical importance of a special
group of carbo- hydrate molecules, the
pharmaceutical industry has been spending
billions of dollars in development of
• “New carbohydrate technology will provide
carbohydrate drugs.
novel products for treating a broad
range of diseases, including immune
disorders, cancer, infectious diseases, and
cardiovascular conditions.”
Biotechnology, Vol 9, July 1991
•“The day may not be far off when
antiadhesive drugs, possibly in the
form of pills that are both sugar-coated and
sugar-loaded will be used to prevent and
(Continued)

Currently over 15 pharmaceutical companies


are in Phase I, II, or III drug testing of
• various carbohydrate drugs
Reperfusion
for treating:
• Influenza
injury • HIV / Aids
• Cancer • Infection / wound
• Thrombosis healing
• Post-surgical
• Diabetes infection
• Stomach ulcers • Epilepsy
• Haemorrhagic • Parkinson’s
colitis disease
Unfortunately, the synthetic carbohydrate
drugs will still have •toxicity
Organ transplants
and the
Essays Biochem 1995;30:59-75
 

Lectins--proteins with a sweet tooth:


functions in cell recognition.
 

Sharon N, Lis H Dept of Membrane Research and Biophysics, Weizmann


Institute of Science, Rehovot, Israel.
 

Lectins, non-enzymic proteins that bind mono- and oligosaccharides reversibly and
with high specificity, occur widely in nature. They come in a variety of sizes and
shapes, but can be grouped in families with similar structural features. The
combining sites of lectins are also diverse, although they are similar in the same
family.The specificities of lectins are determined by the exact shape of the binding
sites and the nature of the amino acid residues to which the carbohydrate is
linked. Small changes in the structure of the sites, such as the substitution of only
one or two amino acids, may result in marked changes in specificity. The
carbohydrate is linked to the protein mainly through hydrogen bonds, with added
contributions from van der Waals contacts and hydrophobic interactions.
Coordination with metal ions may occasionally play a role too. Microbial surface
lectins serve as a means of adhesion to host cells of viruses (e.g. influenza virus),
bacteria (e.g. E. coli) and protozoa (e.g. amoeba): a prerequisite for the initiation
Blocking the adhesion by carbohydrates that
of infection.
mimic those to which the lectins bind prevents infection
by these organisms. The way is thus open for the
development of anti-adhesive therapy against microbial
diseases. Lectin-carbohydrate mediated interactions
between leucocytes and endothelial cells are the first
the most attractive strategy for developing
anti-adhesive thera-peutic agents is to use
soluble forms of the human oligosaccharide
component, which are small and non-
“A striking example of the successful
immunogenic.”
application of antiadhesive, soluble
carbohydrates involved application of a
mixture of sialyated complex N-linked
glycopeptides (500 mg/day) to protect
newborn calvesforfrom
Drug prospects a oligosaccharides
use of lethal dose of
enterotoxic E coli
include otitis 99.” pneumonia, chronic
media,
bronchitis, gastrointestinal diseases, cystitis,
gonorrhea, chlamydia Lancet
and1996;possibly
347:
enhancement of the effects of standardized
1017-21
Eur J ClinMicrobiol 1987Oct;6(5):591-3

Lectin-mediatedbacterial adhesionto human


tissue.
BeuthJ, Ko HL, UhlenbruckG, Pulverer G

Instituteof Hygiene, Universityof Cologne, FRG.

In vitro experiments with frozen sections of human lung and kidney demonstrated that
adhesion of Streptococcus pneumoniae Pn 629 Type 14 and Pseudomonas
aeruginosaATCC 27853 to human cells was mediated by bacterial lectins (adhesins)
with N-acetyl-D-glucosamine/D-galactose or N-acetyl-neuraminic acid specificity.
Blockingof thelectinbindingsites onbacterial surfaces withcompetitive
carbohydrates completely prevented the bacterial adherence, whereas
non-specific carbohydrates (D-mannose, D-xylose) did not inhibit
adherence.
BACTERIA BACTERIA(cont’ VIRUSES
Actinomyces d) Proteus HIV 
naeslundil mirabilis 
Bordetella Pseudomonas Influenza virus 
pertussis   aeruginosa  Parvovirus
Chlamydia Burkholderia Rotavirus
pneumoniae cepacia Salmonella
Citrobacter freundi typhimurium 
--------------------------
 Enterobacter Serratia
aerogenes  ------------
marcescens 
Escherechia coli  Shigella
 Haemophilius dysenteriae FUNGI
influenzae  H S flexneri  Candida
parainfluenza Staphylococcus albicans
Helicobacter pylori aureus S
  Klebsiella saprophyticus  --------------------------
pneumoniae Streptococcus
 Specific oligosaccharides shown to be effective
------------
Mycobacterium
antiadhesive agents inmutans
vitro.  S (Lancet,1996;
tuberculosis
 Specific oligosaccharides
pneumoniae  
shown to
OTHER
be prophylactic347:1017)
or
ANTI-INFECTIVE AGENTS

Further studies of the sugars on host


cells and of bacterial lectins should
lead to the design of better adhesion
inhibitors. One point about the
approach is certain: because different
infectious agents - even different
bacteria within the same strain - can
have a wide variety of carbohydrate
specificities, a cocktail of inhibitors
will undoubtedly be necessary to
prevent or treat the diseases.
Scientific
American: Jan, 1993; p87
AmJ Respir CritCareMed1997Jun;155(6):2102-4

Pseudomonas aeruginosa II lectin stops human


ciliary beating: therapeutic implications of
fucose.
AdamEC, Mitchell BS, Schumacher DU, Grant G, Schumacher U
Department of Human Morphology, University of Southampton, United Kingdom.

Respiratory tract infection by Pseudomomas aeruginosa may be


life-threatening for intensive care patients and patients with
cystic fibrosis (CF). The colonization of airways can be facilitated by bacterial lectins
(carbohydrate-binding proteins) that attach bacteria to the glycoconjugates of the mucosa. We show in
this paper that the fucose-specific lectin P. aeruginosa agglutinin II (PAII) produced by these bacteria can,
in addition to facilitating bacterial adhesion, arrest ciliary beating in human airways in vitro. This inhibitory
effect of the lectin can be abolished by preincubating PAII with its specific sugar, fucose. Furthermore,
ciliary beating is completely restored by addition of fucose 2 h after administration of PAII to cell cultures.
Therefore, adding a simple monosaccharide to nebulizers may improve the
management of P. aeruginosa infection by abrogating the effect of PAII on ciliary beating, thus restoring
part of the nonspecific pulmonary defense mechanisms of the airways. …if fucose treatment
of P.Aeruginosa infections were to be started at an early stage, it
mightbepossibleto control thefurther spreadof theinfection.
Klin Padiatr 2001 Sep-Oct;213(5):285-7
 

Successful treatment of Pseudomonas


aeruginosa respiratory tract infection with
a sugar solution--a case report on a lectin
based therapeutic principle.
von Bismarck P, Schneppenheim R, Schumacher U.
Department of Paediatric Haematology and Oncology, University Hospital
Eppendorf, Germany.

BACKGROUND: Airway infections with Pseudomonas aeruginosa


often represent a life-threatening event in immuno-
compromised patients or patients with Cystic Fibrosis. The
adhesion of this bacterium to surfaces such as the airway epithelium is mediated by two
lectins, sugar binding proteins. In addition to their adhesive properties, these lectins have
been shown to stop human ciliary beating thus compromising the mucociliary clearance as
an important non-specific defence mechanism of the airways. Inhibition of these lectins by
their specific sugars galactose and fucose, respectively, could therefore be of benefit in the
An infant suffering from P.
elimination therapy of P. aeruginosa. CASE REPORT:
aeruginosa airway infection after chemotherapy for
neuroblastoma, which could not successfully be treated by
antibiotics, was subjected to a series of additional galactose /
fucose inhalations, which eliminated the germ as evidenced by
microbiological testing. This is the first report suggesting the effectiveness of
 
 
 
Biol Neonate 1998;74(2):143-162
 

Glycoproteins of the human milk


fat globule in the protection of the
breast-fed infant against
infections.
Peterson JA, Patton S, Hamosh M.
Cancer Research Institute of Contra Costa, Walnut Creek, Calif 94596,
USA.

Nonimmunological components in human milk can


protect breast-fed infants against infection by
microorganisms. The structural and functional characteristics of
four such components are discussed. The mucin inhibits binding of S-
fimbriated Escherichia coli to bucal epithelial cells; lactadherin
prevents symptomatic rotavirus-induced infection;
glycoaminoglycans inhibit binding of human immunodeficiency
Glycoconj J 1995Feb;12(1):1-6

Importanceof lectins for thepreventionof


bacterial infections andcancer metastases.
BeuthJ, Ko HL, Pulverer G, UhlenbruckG, Pichlmaier H

Instituteof Medical MicrobiologyandHygiene, Universityof Cologne, FRG.

Adhesion of bacteria and of metastasizing tumour cells have much in common, especially the
participation of lectins in this process. In the future it might be possible to inhibit the
metastatic process and bacterial adhesion by blocking with lectins specific
for appropriate (oligo) saccharides or glycoconjugates. Initial clinical trials
arevery promising.
Cancer cells have unusual carbohydrates on
their surface, which may account for many of
their invasive properties. Drugs that interfere
with the adhesiveness of abnormal cells may
someday be used in cancer therapies.
Sharon and Lis, “Carbohydrates in Cell Recognition,” Scientific American, January 1993, pgs. 82-
89
• Billions of dollar$ are being
spent to create synthetic
carbohydrate drugs because the
effectiveness of natural
carbohydrates have been
demonstrated repeatedly in
medical research.
• GLYCONUTRIENTS are
available for patients NOW -
Anticancer Res 1997 Mar-Apr;17 (2B):1223-6

Prevention of hepatic metastases


by liver lectin blocking with D-
galactose in colon cancer patients.
A prospectively randomized clinical
trial.
Warczynski p, Gil J, Szmigielski S, Beuth J, Pulverer G MMA Postgraduate
Medical School Warsaw, Poland.

76 colon adenocarcinoma patients (stages 1-3, NO, Mo) were


enrolled into a prospectively randomized clinical trial, 39
patients were perioperatively treated with D-galactose-(therapy
group:1.9 g/kg BW and day) or D-glucose-containing electrolyte
infusions ( control group: n = 37). There were no cases of
perioperative mortality. The complication rate was 17.1%
(therapy group 15.3%; control group: 18.9%). Since tumor
staging and grading were equally distributed for therapy and
control groups, a non stratified statistical analysis yielded:

a) significantly reduced hepatic metastases and


Anticancer Res 1997 Mar-Apr;17(2b):1411-5

Prevention of hepatic
metastases by liver lectin block-ing
with D-galactose in stomach cancer
patients. A prospectively randomized
clinical trial.
Kosik J, Gil J, Szmigielski S, Beuth Jm Pulverer G
Postgraduate Medical School, Warsaw, Poland

80 stomach adenocarcinoma patients (T1-3, NO,MO) were enrolled


into a prospectively randomized clinical study. 40 patients were
perioperatively treated with D-galactose (treatment group:1.9 g/kg
BW and per day) or D-glucose-containing electrolyte infusions
(control group: n = 40). Perioperatively mortality was low (3.7%),
complication rate was 11.2% (treatment group: 12.5%; control
group:10%. Since tumor staging and grading were similarly
distributed for treatment and control groups, a non-stratified
statistical analysis yielded:
J ournal of Surgical Oncology 3(1): 79-88 (1971)

TheEffectof L-FucoseonRatMammaryTumor
Growth. II. InVitro Studies
J ames M. Roseman, A.B., Elizabeth Miller, Ph.D., Murray H. Seltzer, M.D., Daniel Wolfe, B.S., and Francis E
Rosato, M.D.

Different concentrations of L-fucose uniformly produced a suppression in the growth rate and a change in the
morphology of cells grown in tissue culture. The inhibition of growth of these malignant cells
was found to be concentration dependent with 100% inhibition of growth at a
concentration of 50 mg fucose per milliliter of medium and 60% inhibition at a
concentration of 12.5 mg per milliliter medium. Using other sugars that are
components of glycoproteins, it was shownthatmannoseandgalactosecouldalso
depress the rate of growth of these tumor cells in culture. When 0.05 ml of packed tumor
cells used in these experiments was resuspended in 1 ml of mediumand injected into a rat, a tumor grew at
the site of injection. This newtumor exhibited similar growth characteristics and showed the same histological
appearance as the tumor fromwhich the cell line was derived.
Acta Univ Palacki Olomuc Fac Med 1989;122:113-20

Effect of some sugars on the growth


and differenti-ation of MCF-7 cells:
I. Detection of glycosylative changes
using lectin histochemistry.
Kolar Z, Negrini R, Lisato
The effects of lactose, L-fucose, and D-glucose on
differentiation and glycosylation of MCF-7 cells from human
mammary cancer were tested. For determination of glycosylation,
six lectins with various binding specificity were used. The cells
cultivated in the medium with D-glucose alone showed the best
growth.The cells growing in the medium with
L-fucose displayed, at the beginning growth
acceleration which was followed by a rapid
onset of necrotization. A decreased content of D-
glucose usually resulted in an accelerated differentiation and a
more pronounced secretory activity of cells. Expression of
binding sites for lectins PNA and WGA was higher in cultures
with elevated proliferation and reduced differentiation, DBA bound
Experientia 1989 Jun 15;45(6):584-8

Blocking of lectin-like adhesion


molecules on pulmonary cells
inhibits lung sarcoma L-1
colonization in BALB/c-mice.
Roszkowski W, Beuth J, Ko HL, Uhlenbruck G, Pulverer G
National Institute of Lung Diseases and Tuberculosis, Warsaw,
Poland.

Adhesion and inhibition experiments with pulmonary cells o


f BALB/c-mouse origin and syngeneic sarcom a L-1 cells
indicated that L-fucose specific lectin-like adhesion molecules,
presumably situated on pulmonary cell surfaces are (at
least partly) responsible for the specificity of this cell-cell
interaction. Addition of specific sugars and glycoconjugates
(L-fucose and fucoidan, respectively) to the incubation medium
evidently inhibited the ad-hesion process as quantified using
radiolabelled tumor cells . Unspecific carbohydrates (e.g.D-
galactose) did not affect the cellular interaction. In vivo,
repeated administration of fucoidan (but not of unspecific
Oral Presentation: ComprehensiveCancer Carell: IntegratingComplementary&AlternativeTherapies, Sponsoredby
Center for Mind-BodyMedicine&National Cancer Institute, attheHyattRegencyinCrystal City, Arlington, VA, June1999.
A PILOT SURVEY: STANDARD CANCER THERAPY COMBINED WITH
NUTRACEUTICAL DIETARY SUPPLEMENTATION IMPROVES TREATMENT
RESPONSES ANDPATIENT QUALITY OF LIFE.
G. Hyland, M.D., D. Miller, M.T., Medcenter One, Dept. RadiationOncology, Bismarck, NorthDakota.
In thousands of cancer cases evaluated by H. Foster, 87%percent of those with "spontaneous remissions" had made major dietary changes prior to tumor regression. The
Dietary Supplement Health Education Act of 1994resulted in millions of US citizens addingaplethoraof supplements to their diets. A favorableresponseby 5patients that
failed all cancer therapy was noted after it was stopped. We found that they had consumed glyconutrient, phytonutrient and phytogenin containingdietary supplements. A
search revealed that Dr. Busbee et. al 1994found a glyconutrient inthesedietsupplements increasedIL-1, IL-6, INFandTNFproductioninmonocytecultures. Dr. Seeet. al
1999 reported enhanced NK lymphocyte cytolytic function in response to multiple glyconutrients. Dr. Barhomi et. al 1997 found glyconutrients increased intracellular
reduced-glutathioneprotection50%inliver cells. Suchactivity provides apotential differential effectfor tumor cell destructionandnormal cell protection.
To increase our observations, patients with malignancies were solicited from a 3 state area and 127 volunteered
to add nutraceuticals to their diet. 100 patients returned a quality of life survey focusing on weight loss, fatigue,
nausea, vomiting, pain control, ability to complete treat-ments on schedule, physical activity and sense of well
being. 40% of the group had failed standard therapy and were in a state of progressive disease (sent home to die).
60% were starting radiation or chemotherapy. 85% reported improvements in the above clinical parameters.
The phytogenin supplement contains plant sterols for nutrient based endocrine support. Ovarian, breast, uterine, and prostate malignancy
patients werediscouragedfromtakingthis nutrient. Someelectedto add thephytogenin to their dietandthey reportedthebestpreservationof
appetite, muscle mass, and had the least side-effects during treatment. Patients with a diagnoses of ovarian carcinoma, astrocytoma grade IV,
lymphomawithmildmarrowsuppression, a massivepelvic myxosarcoma, andcolonadenocarcinoma with brainmetastasis hadunprecedented
responses.
: Nutraceutical dietary supplements:(Glyconutrients, Phytonutrients andPhytogenins)
CONCLUSIONS

♦ Do notinhibittumor cell destructionby radiationandchemotherapy


♦ Enhancetumor cell destruction
♦ Protectnormal cells fromradiationandcytotoxic damage
♦ Inducereductions intumor mass inmalignancies resistantto all treatments
♦ Improve quality of life for patients by reducing treatment toxicity and side effects from
radiationandchemotherapy.
A formal, controlled clinical study is warranted to further evaluatetheeffects of nutraceutical dietary supplementation in
combinationwithstandardcancer therapy.
Clin Exp Rheumatol 1995 Mar-Apr;13(2):243-6

Fucose concentrations in sera from patients with


rheumatoidarthritis.
Kamel M, Serafi T Dr. Fakhry Hospital, Dhahran, Saudi Arabia.
The clinical significance of L-fucose was investigated in serumof a well characterized cohort of
135 RA patients and 60 healthy controls. In RA patients, serumL-fucose was significantly decreased to a
mean of 5.57 +/- 0.97 mg%, (range 2.2-7.5 mg%), compared with 7.5 +/- 1.04 mg%(range 5.7-9.8 mg%) (p <
0.001) innormal controls. InearlyRA serumL-fucosewas significantlydepressedto ameanof 6.08mg%, a
value which was significantly higher than the mean concentration of L-fucose in patients with advanced
RA. SerumL-fucose was significantly correlated with the rheumatoid disease activity, duration, number of
involved joints, and bone erosions. No statistically significant difference was found between seropositive
and seronegativeRA patients. However, asignificantdifference(p<0.001) betweenfemale(5.57mg%) and
male(6.59mg%) patients with advancedRA, andbetweenmale(6.08mg%) andfemale(5.99mg%) patients
These findings suggest that serum L-fucose is
with early RA was found.
depressed in patients with rheumatoid arthritis, a promising
observation since L-fucose is a safe and simple natural sugar. It may be
usedas anadditional parameter andas anindicator for thediseaseactivity inthefollowupof patients with
rheumatoidarthritis.
J Pediatr Gastroenterol Nutr, Vol, 26, No. 5, May 1998

N-Acetyl glucosamine– anovel “nutraceutical”


therapyfor IBD.
Salvatore S, Heuschkel R, Davies S, Walker-Smith J , Murch S; Royal Free Hospital, London, UK.
Background: tissue damage in IBD occurs by inflammatory degradation of extracellular matrix, notably glycosaminoglycans
We nowreport thetherapeutic effects of matrix restoration
(GAG – Lancet 1993; 341: 711-714).
with N-acetyl glucosamine (NAG), a “nutraceutical” substrate for GAG production. In
addition to its role as a fuel for fibroblast repair, there is recent evidence that NAG may act intracellularly as an antagonist of
O-phosphorylation and may thus regulate inflammatory pathways (Annu Rev Biochem1997; 66: 313-335). We have thus
stained biopsies for GAGs and used the lectin wheatgermagglutinin (WGA) to detect intracellular NAG.
Results: Rectal administration of NAG (1.5-2g bd) to 9 children with therapy-resistant distal colitis induced clinical remission in
4, improvement in 3 and no effect in 2. Biopsies before and after treatment showed histological improvement in all tested, with
a striking increase in GAG density and intrapithelial WGA staining. Oral NAG therapy, in combination with existing
therapies, was also commenced in 11 children with severe small intestinal and colonic disease, including 7 with
critical strictures. 8/11 have shown improvement, while 3 have required surgical resection. 6/7 with treatment-resistant
strictures showed marked resolution of symptoms, with endoscopic or radiological improvements in 4/6. GAG density and
WGA staining was enhanced in all, to an extent greater than in other children treated with steroids or enteral nutrition.
Discussion: This first uncontrolled trial suggests that NAG is potentially of
therapeutic efficacy in resistant IBD. Its mode of action is distinct from
conventional therapies, and its lack of known adverse effects makes it
particularly suitablefor pediatric use.
Aliment Pharmacol Ther 2000 Dec;14(12):1567-79

A pilot study of N-acetyl glucosamine, a nutritional


substrate for glycosaminoglycan synthesis, in paediatric
chronic inflammatory bowel disease.
Salvatore S, Heuschkel R, Tomlin S, Davies SE, Edwards S, Walker-Smith J A, French I, Murch SH
University Department of Paediatric Gastroenterology, Royal Free, London, UK.
BACKGROUND: The breakdown of glycosaminoglycans is an important consequence of inflammation at mucosal surfaces, and inhibition of
metalloprotease activity may be effective in treating chronic inflammation. AIM: To report an alternative approach, using
the nutriceutical agent N-acetyl glucosamine (GlcNAc), an amino-sugar directly
incorporated into glycosaminoglycans and glycoproteins, as a substrate for tissue
repair mechanisms. METHODS: GlcNAc (total daily dose 3-6 g) was administered orally as adjunct therapy to 12 children with
severe treatment-resistant inflammatory bowel disease (10 Crohn's disease, 2 ulcerative colitis). Seven of these children suffered from
symptomatic strictures. In addition, similar doses were administered rectally as sole therapy in nine children with distal ulcerative colitis or
proctitis resistant to steroids and antibiotics. Where pre- and post-treatment biopsies were available (nine cases), histochemical assessment
of epithelial and matrix glycosaminoglycans and GlcNAc residues was made. FINDINGS: Eight of the children given oral GlcNAc showed
clear improvement, while four required resection. Of the children with symptomatic Crohn's stricture, only 3 of 7 have required surgery over a
mean follow-up of > 2.5 years, and endoscopic or radiological improvement was detected in the others. Rectal administration induced
remission in two cases, clear improvement in three and no effect in two. In all cases biopsied there was evidence of histological improvement,
and a significant increase in epithelial and lamina propria glycosaminoglycans and intracellular GlcNAc. CONCLUSIONS:
GlcNAc
shows promise as an inexpensive and nontoxic treatment in chronic inflammatory
bowel disease, with a mode of action which is distinct from conventional treat-
ments. It may havethe potential to be helpful in stricturing disease. However, controlled trials
and an assessment of enteric-release preparations are required to confirmits efficacy and establish indications for use.
The In Vitro Immunomodulatory Effects
of Glyconutrients on Peripheral Blood
Mononuclear Cells of Patients with
Darryl M.Chronic
See,M.D, PaulFatigue
Integ Physio and Behav
Jeremiah Tilles, MD Sci,Jul-Sep 1998, Syndrome
Cimoch,MD, Shioweh
Vol. 33,
Chou, Jennifer Chang,
1
University of California, Irvine 2 Center for Special
No.3,280-287
In h umans, eightIrvine,
Immunology, monosa ccharides are required for the
California synthesis of
glycoproteins. Dietary supplements that supply these crucial sugars are known
as glyconutrients. A glyconutrientcompoundwas addedto Peripheral BloodMononuclear Cells
(PBMC) isolated from normal controls and patients with the Chronic Fatigue Syndrome (CFS), a
disease associated with immune dysregulation. The in vitro immunomodulatory effects were
investigated. Cell surface expression of the glycoproteins CD5, CD8, and CD11a were significantly
lower inpatients withCFS comparedto normal controls. Additionof glyconutrienthomogenate
to PBMC from patients with CFS stimulated with phytohemagglutinin significantly increased
the expression of each glycoprotein. Furthermore, natural killer (NK) cell function was
reduced in CFS patients. The glyconutrient preparation significantly enhanced NK
cell activity versus human herpes virus 6(HHV-6)-infected H9 cells in an 8 h 51Cr release
assay compared to placebo for PBMC from patients with CFS (p< .01). Finally, apoptosis was
significantly higher in patients with CFS. The percentage of apoptotic cells was
significantly decreased in PBMC frompatients with CFS that had been incubated for 48h with
glyconutrients. Thus, glyconutrients improvedabnormal immuneparameters invitro
inpatients withCFS.
The Effects of Dietary Supplements on Lupus: A
Retrospective Survey
KathrynDDykman; Cindy R Ford; CatherineMTone
Proceedings of theFisher Institutefor Medical Research. 1;1:1997. Page26-30.

Twenty-six subjects with a positive diagnosis of lupus agreed to complete a retro-


spective questionnaire designed to assess their response to dietary supplements. The subjects (25 women and
one man) had a mean age of 42years and had been taking supplements for an averageof 13months. They all
reported a significant improvement in their overall condition since beginning dietary
supplementation. Of the 14 symptoms of lupus which were surveyed, statistically
significant improvement were noted in the following symptoms: aching joints, fever,
prolonged or extreme fatigue, arthritis, kidney involvement, and hair loss. Subjects also
reported a statistically significant decrease in number, frequency and severity of flares. In
addition, they experienced significant improvement in all activities that were assessed,
including physical activities, work, family responsibilities, hobbies, and self-care. They
enjoyed these improvements even in light of a significant reduction in their use of non-
steroidal anti-inflammatories, analgesics, and narcotics. These results indicate lupus
patients may experienceanenhancedquality of lifewiththeuseof dietary supplements.
J Cardiovasc Pharmacol 1993Jul;22(1):74-81
Reductionof myocardial ischemic reperfusioninjury by
sialylatedGlycosphingolipids, gangliosides.
Maulik N, Das DK, Gogineni M, Cordis GA, Avrova N, Denisova N
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110.

Gangliosides, sialic acid-containingglycosphingolipids, arelocalizedmostlyto the


outer leaflet of the lipid bilayer in the plasma membrane, particularly in brain..
Gangliosides reduce edema formation, restore glucose metabolism, and increase
cerebral blood flow after focal ischemia in the rat brain. We wished to determine
whether gangliosides could also reduce myocardial ischemic and reperfusion
injury. Isolated rat heart perfused by Langendorff technique was pretreated with gangliosides (1 microM) purified fromthe rat
brain. After 15-min perfusion with gangliosides, hearts were made ischemic for 30 min by termination of coronary flow, followed
by 60-min reperfusion. Ganglioside-treated heart exhibited better myocardial preservation, as evidenced by reduction in
creatine kinase release and lipid peroxidation product formation enhanced coronary flow and contractile functions [left
ventricular developed pressure (LVDP) and maximumfirst derivative of LVDP, LVdp/dtmax]. In addition, gangliosides reduced
the hydroxyl radical formed during reperfusion of ischemic myocardium, as shown by high-performance liquid chromatography
(HPLC)-electrochemical detection technique. In vitro studies demonstrated that these gangliosides were direct scavengers of
superoxide anions (IC50 0.8 microM), and hydroxyl radicals (IC50 10 microM), as well hypohalite radicals (IC50 0.7 microM).
Furthermore, ganglioside pretreatment was accompanied by reduced intracellular calcium overloading during ischemia and
The results of this study thus suggest that
reperfusion as compared with untreated controls.
gangliosides can reduce ischemic reperfusion injury in isolated heart, probably by
inhibiting intra-cellular calciumoverloading and/or by directly scavenging the free
radicals generatedduringreperfusionof ischemic myocardium.
Ann Thorac Surg 1996 Nov;62(5):1295-300

Blockade of selectin-mediated leukocyte adhesion


improves postischemic functioninlambhearts.
MiuraT, NelsonDP, SchermerhornML, Shin'okaT, ZundG, HickeyPR, NeufeldEJ, Mayer JE Jr
Department of Cardiovascular Surgery, Children's Hospital, Boston, Massachusetts 02115, USA.
BACKGROUND: Leukocyte-endothelial interactions appear to have a important role in ischemia/reperfusion injury and are mediated by specific
leukocyte and endothelial adhesion molecules. The selectins are adhesion molecules found on leukocytes (L-selectin) and endothelium(P and
E selectin) that bind to oligosaccharide ligands containing fucose and sialic acid to mediate leukocyte rolling on the endothelium. Fucoidin is
a nontoxic sulfated fucose oligosaccharide derived fromseaweed that blocks the selectins. METHODS: We
tested the effects of fucoidin in an isolated blood-perfused neonatal (age range, 3 to 7 days; mean age, 4.3 days) lamb heart model undergoing
2 hours of cold cardioplegic ischemia. In group F (n =8) fucoidin (30 mg/L) was added at initial reperfusion. Group C (n =9) received only
cardioplegia with no reperfusion intervention. Isovolumic maximumdeveloped pressure and the maximumpositive and negative first derivatives
of pressure were measured using a catheter-tip transducer in an intraventricular balloon before ischemia and at 30 minutes of reperfusion.
Coronary blood flow, myocardial oxygen consumption, and white blood cell counts in the circulating blood were also measured. RESULTS: Percent
recoveries of baseline maximum developed pressure and maximumpositive and negative first derivatives of pressure in group F (86% +/- 5%,
81% +/- 10%, and 74% +/- 8%, respectively; mean +/- standard deviation) were higher than in group C (77% +/- 5%, 70% +/- 9%, and 65% +/-
6%; p <0.05). Group F postischemic coronary blood flow was greater (190% +/- 35%) than in group C (102% +/- 10%; p <0.05). Recovery of
myocardial oxygen consumption in group F (86% +/- 14%) was greater than group C (72% +/- 11%; p <0.05). Postischemic white blood cell
count in group F (88% +/- 4%) was greater than in group C (81% +/- 5%; p <0.05). CONCLUSIONS: Selectin blockadewith
fucoidin resulted in better recovery of left ventricular function, coronary blood flow, and
myocardial oxygen consumption after cold ischemia, despiteahigher circulatingwhiteblood
cell count. These data support the hypothesis that endothelial-leukocyte interactions play an
important role in ischemia/reperfusion and suggest that selectin blockade may be a useful
therapeutic strategy.
BiochemBiophys Res Commun1999Feb16;255(2):189-93

Human glycosylation disorders and sugar


supplementtherapy.
Freeze HH
The BurnhamInstitute, La J olla, California 92037, USA.

Some genetic defects in protein glycosylation can be treated


effectively with dietary supplements of monosaccharides. An
easy screening test and non-toxic therapy for potentially lethal
disorders should encourage physicians to search for more patients with glycosylation
disorders. It should also stimulate research on the occurrence and availability of
monosaccharides used for glycoconjugate synthesis and for vertebrate models to study
their utilization.
Biochem Mol Med 1997 Apr;60(2):127-33
 

Oral ingestion of mannose elevates


blood mannose levels: a first step
toward a potential therapy for
carbohydrate-deficient
Alton G, Kjaergaard S, Etchison JR, Skovby
Burnham Institute, La Jolla, California
glycoprotein
F, Freeze HH ;

syndrome
 
type I.
Carbohydrate-deficient glycoprotein syndrome type I
(CDGS) is an inherited metabolic disorder with
multisystemic abnormalities resulting from a failure to add
entire N-linked oligosaccharide chains to many
glycoproteins. Fibroblasts from these patients also abnormally glycosylate
proteins, but this lesion is corrected by providing 250 microM mannose to the
culture medium. This correction of protein glycosylation suggests that providing
dietary mannose to elevate blood mannose concentrations might also remedy
some of the underglycosylation observed in these patients. We find that ingested
mannose is efficiently absorbed and increases blood mannose levels in both
normal subjects and CDGS patients. Blood mannose levels increased in a dose-
dependent fashion with increasing oral doses of mannose (0.07-0.21 g
mannose/kg body weight). Peak blood mannose concentrations occurred at 1-2 h
following ingestion and the clearance half-time was approximately 4 h. Doses of
0.1 g mannose/ kg body weight given at 3-h intervals maintained blood mannose
conentrations at levels 3- to 5-fold higher than the basal level in both normal
J ClinInvest1996Mar 15;97(6):1478-87

Mannosecorrects alteredN-glycosylationin
carbohydrate-deficientglycoproteinsyndrome
fibroblasts.
PanneerselvamK, FreezeHH; LaJollaCancer ResearchFoundation,
Type I carbohydrate-deficient glycoprotein syndrome (CDGS) patients fail to add entire N-linked oligosaccha-
ride chains to some serumglycoproteins. Here we showthat four CDGS fibroblast cell lines have two related
glycosylation abnormalities. First, they incorporate 3-10-fold less [3H] mannose into proteins, and, second,
the size of the lipid-linked oligosaccharide precursor (LLO) is much smaller than in controls. Addition of
exogen-ous mannose, but not glucose, to these CDGS cells corrects both the lowered [3H] mannose
incorporation and the size of LLO. These corrections are not permanent, and the defects immediately
reappear when mannose is removed. To explore further the basis of mannose correction, we analyzed the
amount of 3H- labeled LLO intermediates. Except for dolichol-P-mannose, other precursors, including
mannose, mannose-6-phosphate, mannose-1-phosphate, and GDP-mannose, all showed a 3-10-fold
decrease in CDGS cells. Thus, there are no obvious lesions in the intracellular conversion of mannose into
LLO, and, once inside the cell, [3H]mannose appeared to be metabolized normally. Initial velocities of
[3H]mannose uptake were two-to threefold less in CDGS cells compared with controls, and this slower
transport may partially explain the re-duced [3H]mannose incorporation in CDGS cells. Since we previously
showed that the enzymes converting glucose to mannose-6-phosphate appear to be normal, our results
suggest that cells may acquire or generate mannose in other ways. Although we have not identified the
primary defect in CDGS, these studies showthat intracellular mannose islimited
and that some patients might benefit from including mannose in their
regular diets.
J ClinInvest1998Apr1;101(7):1414-20

Carbohydrate-deficient glycoprotein syndrome


type Ib. Phosphomannose isomerase deficiency
andmannosetherapy.
Niehues R, Hasilik M, Alton G, Korner C, Schiebe-Sukumar M, Koch HG, Zimmer KP, Wu R,
Harms E, Reiter K, von Figura K, Freeze HH, Harms HK, Marquardt T
Klinik und Poliklinik fur Kinderheilkunde, 48149 Munster, Germany.
a new type of
Phosphomannose isomerase (PMI) deficiency is the cause of
carbohydrate-deficient glyco-protein syndrome (CDGS). The disorder
is caused by mutations in the PMI1 gene. The clinical phenotype is characterized by protein-
losing enteropathy, while neurological manifestations prevailing in other types of CDGS are
absent. Using standard diagnostic procedures, the disorder is indistinguishable from CDGS
type Ia (phosphomannomutase deficiency. Daily oral mannose administration
is a successful therapy for this new type of CDG syndrome
classifiedas CDGS typeIb.
Blood 1999 Dec 15;94(12):3976-85

Correction of leukocyte adhesion


deficiency type II with oral Fucose.
Marquardt T, Luhn K, Srikrishna G, Freeze HH, Harms E, Vestweber D
Klinik und Poliklinik fur Kinderheilkunde and the Institut fur Zellbiologie, ZMBE,
Universitat Munster, Munster, Germany.

We describe a simple, noninvasive, and effective


therapy for leukocyte adhesion deficiency type II (LAD
II), a rare inherited disorder of fucose metabolism. This
disorder leads to an immunodeficiency caused by the absence of
carbohydrate-based selectin ligands on the surface of neutrophils as well as
to severe psychomotor and mental retardation. The fucosylation defect in LAD
II fibroblasts can be corrected by addition of L-fucose to the culture medium.
This prompted us to initiate dietary fucose therapy on a patient with LAD II.
Oral supplementation of fucose in this patient induced the
expression of fucosylated selectin ligands on neutrophils and core
fucosylation of serum glycoproteins. During 9 months of
treatment, infections and fever disappeared , elevated
neutrophil counts returned to normal, and
psychomotor capabilities improved.
Blood 2001 J an 1;97(1):330-2

Discontinuation of fucose therapy in LADII causes rapid


loss of selectinligands andriseof leukocytecounts
Luhn K, Marquardt T, Harms E, Vestweber D
Institute of Cell Biology, ZMBE, University of Munster; Max-Planck-Institute for Physiological and Clinical Research, Munster,
Germany; and Klinik und Poliklinik fur Kinderheilkunde, Munster, Germany.

Leukocyte adhesion deficiency type II (LADII) is a rare inherited disorder of


fucose metabolism. Patients with LADII lack fucosylated glycoconjugates, including the carbohydrate
ligands of the selectins, leading to an immunodeficiency caused by the lack of selectin-mediated leukocyte-
endothelial interactions. A simple and effective therapy has recently been described
for LADII, based on the administration of oral fucose. Parallel to this treatment the lack
of E- and P-selectin ligands on neutrophils was corrected, and high peripheral neutrophil counts were reduced
to normal levels. This study reports that discontinuation of this therapy leads to the
complete loss of E-selectin ligands within 3 days and of P-selectin ligands
within 7 days. Peripheral neutrophil counts increased parallel to the decrease of
selectin ligands. Selectin ligands reappeared promptly after resumption of the
fucose therapy, demonstrating a causal relationship between fucose
treatmentandselectinligandexpressionandperipheral neutrophil counts.
FASEB J 1987 Dec;1(6):462-8
 

Trafficking of lysosomal enzymes.


 

Kornfeld S.
Department of Internal Medicine, Washington University School of Medicine, St.
Louis, Missouri 63110.
 

The targeting of lysosomal enzymes from their site


of synthesis in the rough endoplasmic reticulum
(RER) to their final destination in lysosomes is
directed by a series of protein and carbohydrate
recognition signals on the enzymes. Lysosomal enzymes, along
with secretory and plasma membrane proteins, contain amino-terminal signal sequences
that direct the vectorial discharge of the nascent proteins into the lumen of the RER. The
three classes of proteins also share a common peptide signal for asparagine
glycosylation. The next signal is unique to lysosomal enzymes and permits their high-
affinity binding to a specific phosphotransferase that catalyzes the formation of the
mannose 6-phosphate This carbohydrate
recognition marker.
determinant allows binding to specific receptors that
translocate the lysosomal enzymes from the Golgi
complex to an acidified prelysosomal compartment.
There the lysosomal enzymes are discharged for
final packaging into lysosomes. Two distinct mannose 6-phosphate
 
Surg Clin North Am 1999 Dec;79(6):1385-
416
 

  Immune dysfunction in trauma.


 
Napolitano LM, Faist E, Wichmann MW, Coimbra R
Department of Surgery, Ludwig Maximilians University, Klinikum
Grosshadern, Munich, Germany.
 
This article documents that all immunomodulation strategies for
patients sustaining traumatic injury are still under intense
investigation. Although we can speculate that combination
strategies may be more beneficial than single-agent
immunomodulation approaches, comprehensive clinical studies
are required to determine efficacious immune therapy for
trauma The only strategy available to
patients.
clinicians caring for trauma patients is
immunonutrition, and this should be strongly
considered as a rational approach to improve
Proc Natl Acad Sci USA 1998 Oct 27;95(22):
13188-93
CM101-mediated recovery of walking
ability in adult mice paralyzed by spinal
cord injury.
Wamil AW, Wamil BD, Hellerqvist CG.Dept of Surgery, Vanderbilt
University, Nashville, TN
CM101, an antiangiogenic polysaccharide derived
from group B streptococcus, was administered by
i.v. injection 1 hr post-spinal-cord crush injury in an
effort to prevent inflammatory angiogenesis and
gliosis (scarring) in a mouse model. We postulated that
gliosis would sterically prevent the reestablishment of neuronal
connectivity; thus, treatment with CM101 was repeated every
other day for five more infusions for the purpose of facilitating
regeneration of neuronal function. Twenty-five of 26 mice
treated with CM101 survived 28 days after surgery,
and 24 of 26 recovered walking ability within 2-12
days. Only 6 of 14 mice in the control groups
6th International Congress onAnti-AgingandBio-Medical Technology, Las Vegas, Nevada, Dec 1998
WardB, Kaats G, Mcdaniel C, DykmanK, BoydS, McAnnalley B, Hall J, McDaniel HR

BIO-MARKERS OF AGING ARE IMPROVEDBY A


NUTRACEUTICAL-AUGMENTEDOPTIMAL HEALTHPLAN
Parameter Healthy Nutraceutical+
Intervention PlanEffect
1. Musclemass Increase Increase
2. Percentbody fat Decrease Decrease
3. Strength Increase Increase
4. Aerobic capacity Increase Increase
5. Bloodpressure Decrease Decrease
6. Bonedensity Increase Increase
7. Bloodglucosetolerance Increase Increase
8. Cholesterol / HDL ratio Decrease Decrease
9. Basal metabolic rate Increase ?
10. Body temperatureregulation Increase ?
( ? ) Has notbeenevaluated. Nutraceuticals includedglyconutrients, phytonutrients, diosgenins
• No miracles involved, just an essential group of
saccharide nutrients that we didn’t know were
necessary or missing until 1996.
• If anything, it represents an under-estimation
by scientists and doctors of the body’s
incredible ability to fix and maintain itself!
• The list is both extensive and quite varied in
• Diabetes
the • Dyslexia
medical literature. • Urinary
infections
• Heart • Otitis media
disease • URI
• Candida
• Hepatitis infection • Stroke
C
• Cancer • Asthma • Cerebral
Palsy
• Autism • Menopause
• Organ
• ADD / • Tay-Sach’s
OBVIOUSLY ONLY A FEW EXAMPLES OF
THE MEDICAL RESEARCH CAN BE
INCLUDED ON THIS CD SO….
Check out the NEW nutrition science
site at:

Additional information on Glyconutrients as


well as other nutra-ceuticals can be
reviewed at the new Glyco-Science website.

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