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Nutrition: on Nutraceuticals

Supplements 101:
the Who What and Why of Dietary Supplement Manufacturing and Use in Clinical Practice

IATROGENIC AND OTC HYPOCHLORHYDRIA
tabs also not good for pts who are taking acid blocking meds (tagamet, etc)
without acid: don't digest proteins, don't absorb minerals
shakes bottle of tabs: as good as a maraca if you don't have acid
blocked acids in rats: made them more allergic to foods
http://www.ncbi.nlm.nih.gov/pubmed/17227952?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=3
he asked the researcher, they're doing it in humans, same results

Dr Alan L. Miller, ND
Bastyr grad 1989
practiced in Spokane after graduating x4yrs
got hired by Thorne in Sandpoint Idaho, been there x16 years
http://www.thorne.com/
brown vest over white pinstriped shirt with tie, gray pants
salt and pepper goatee, glasses, balding but not bald, lean, medium build

REASONS TO SUPPLEMENT
correct def, enhance fx,
make up for diet, lifestyle, enhance normal, make up for genetic defect

defined as: oral, non-homeopathic, tablet, capsule, powder or liquid

allergens the law requires to be on label: dairy wheat soy fish shellfish
lots of ingredients in supps that you'll never know unless you find right person to ask

supplement provider mb several steps down manufacturing line from source
manufacturers don't know, think it's no big deal, accept manufacturer's certificate of analysis

TABLETS
pro: can get lots of ingredients in
relatively easy to swallow
con: may not dissolve well
mb coated with glaze, solvent or other allergenic substance (corn)
glaze is shelac: bug excrement mixed with solvent, same stuff as used on furniture
vegetable protein coating
zene? zien? corn based protein sprayed on tablets
must put binder in powder to hold capsule together

CAPSULES
pro: tend to be more pure
ready to dissolve
con: less ingredient wt per cap
may need to take more of them
may have unpleasant taste dt capsule or powder on sfc
manufacture: bovine vs vegetable
veg are cellulose from pine trees

POWDERS
pro: can get a lot of nutrients per dose
ready to go into solution
easy ped dosing
con: messy
must mix with liquids
may taste bad

LIQUIDS
pro: already liquid form
ready to absorb
easy ped dosing
con: taste, smell
needs preservative (tinctures: alcohol is the preservative)
temptation to be sloppy with dosing

GELCAPS
pro: slippery, easy to swallow
easy way to dose liquid in capsule
avoid taste issues
con: mb large
smaller dose compared to liquid
most still made from bovine-derived gelatin

VIT C MANUFACTURE
none from citrus
synthetic from natural source
starting material is starch, usu corn
dextrose easily converted to ascorbic acid, purified, crystallized
no corn left in these, corn allergy will not be provoked
some people still react: some manufacturers dilute their product with corn starch
"whole food concentrate" is not just food
corn starch is compressible and helps bind the tablet together
that corn starch doesn't have to be on label because it was added by "someone else"

VITS FROM FERMENTATION
specific material fermented with specific microbe
ribose-->riboflavin
cobalamin
folate
gaba product made by lactobacillus
vitamin K

MINERALS
usually chelated
= reacted compound of inorganic mineral with organic substance
chelate means claw
organic binders used: organic acid, amino acid, peptide
makes mineral more soluble, hopefully more absorbable
all + charge nutrients compete for absorption
his feeling is that body will take what it needs

CALCIUM
4% of earth's crust inorganic
CaCO3 mined from earth is 40% calcium
**absorption is acid dependent
tums neutralizes acid via calcium and yields CO2
citrate, malate article by Lyn Patrick ND in Alt Med Review 1999 look it up
Comparative absorption
http://www.chiro.org/nutrition/ABSTRACTS/Comparative_Absorption_of_Calcium.shtml
**best: bisglycinocalcium (glycinate), citrate malate better than straight citrate
worst: oxalate, hydroxyapatite, ca carbonate, tricalcium phosphate
single dose over 500mg you don't absorb it all
study compared 500 to 1200 mg dose of same form and found higher blood levels with lower dose
*multiple small doses throughout day is best
everybody loses bone density during menopause
build bone early in life
don't trust labels that list forms without giving amounts:
assume they're using carbonate (cheap) if it's in the list
"amino acid chelate" not guaranteed to be glycinate, could be any
some docs say take antacid for calcium supplement
TUMS EX 750 = 750mg calcium carbonate-->750 x .4 = 300mg actual dose

MAGNESIUM
citrate leads to greatest serum concentration
oxide no different than placebo (didn't absorb any)
amino acid chelate led to negligible increase in blood Mg levels
if form is well absorbed then will be less stool softening
mg glycinate one of the best absorbed, right up there with citrate malate
glycinate mb better tolerated, less diarrhea

ZINC
most studied of the trace minerals
was much studied, two camps: picolinate vs citrate best absorbed
mineral binding ligands in body
looking at picolinate dt acrodermatitis enteropathica
(can't absorb zinc dt not producing enough picolinic acid in pancreas)
Comparative absorption of zinc picolinate
http://www.ncbi.nlm.nih.gov/pubmed/3630857
Barrie on this study started Great Smokies Lab which is now ....
1987 study, other NDs on study
incr in hair, urine, RBC levels of zinc with picolinate only

CHROMIUM PICOLINATE
researched dt diabetes and wt loss uses
Comparison of acute absorption of commercially available chromium supps, DiSilvestro

B-VITAMINS
active cofactors for biochem rxns
vitamins often supply inactive forms, also inactive in food
must be converted in body to active form

B6
often supplied as pyridoxine HCl
must be phosphorylated in liver
P5P is active cofactor: pyridoxal 5'-phosphate is "tissue ready", aka PLP
image of P5P: six sided resonant ring with phosphate group
what if liver function not so great?
conversion inhibited in liver dysfx/dz
nice research on pts with cirrhosis: low B6 levels

B12
cyano or hydroxy cobalamin
active forms: adenosycobalamin and methylcobalamin
these two forms interconvert
adenocobalamin has minor activity in fatty acid conversion: odd number chains
methylcobalamin is methyl donor in methionine metabolism (muy importante)
methylates homocysteine
homocysteine can also be converted to cysteine and taurine with enough B6 on hand

FOLATE
active form: 5-methyltetrahydrofolate (end of metabolic line)
methyl donor in methionine homocysteine cycle
60% of US pop has genetic polymorphism in enzymes to activate folate
about 17% are homozygous
folinic acid is an intermediate that is also involved in purine manufacture-->DNA
high homocysteine linked to: MI, stroke, miscarriage, depression
important supplement in pregnancy!!!
folic acid-->DHF-->THF-->methylene THF-->5-MTHF-->can circle back to THF making methionine
MTHFR is enzyme btw 5MTHF and methylene THF, goes both ways, also acts as hydrogen donor
can be antioxidant
if high oxidative stress, this enzyme goes there and lowers folate levels
(oxidative stress: smoking, drinking)
**high levels of synthetic folic acid may cause cancer
mbdt genetic polymorphism that doesn't allow conversion of folic to useful form

tetrahydrobiopterin = BH4 = THB, is hydrogen donor and more
cofactor in both enzymes
to convert trytophan-->5HTP-->ser-->N-acetylseratonin-->melatonin,
also in phenylalanine-->tyr-->dopa-->norepi-->epi
can only be recycled if you have enough folate
SAMe can take epi to melatonin
so giving folate-->incr TH4 may help with depression!!!
SSRIs don't work in many people mb dt this: not enough serotonin to not reuptake
other cofactors in this process: vit C, iron
lots in US don't get enough vit C

5MTHF improves vascular function
nitric oxide (NO) essential for vascular fx
produced in vascular endothelial cells
5MTHF works with BH4 as cofactor to produce NO
BH4 in ECs is cofactor with vit C for NO manufacture
BH4 can stand in for tetrahydrobiopterin in this process
tetrahydropbiopterin two rings structure with several nitrogens, two OH groups on tail
some pts don't have MTHFR enzyme and benefit highly from activated 5MTHF
drug called Deplin: "medical food"? legal loophole
by prescription only: Deplin contains 7.5 mg dose of 5MTHF
http://www.deplin.com/
Dietary management of depression with Deplin® regulates all 3 monoamine neurotransmitters associated with mood by providing the increased requirements for folate in the brain.
L-methylfolate is needed by depressed patients with suboptimal folate
to regulate the synthesis of monoamines
(serotonin, norepinephrine and dopamine)
also known as a trimonoamine modulator (TMM)
L-methylfolate manages trimonoamine neurotransmitter synthesis,
when taken with antidepressants improves benefits

legal limit for nonprescrip 5MTHF is 1mg
presumably dt risk of missing B12 need
7.5mg deplin = about 4 of 1 mg capsules
can I find OTC 1mg supp???? yes, he can't remember the brand
http://en.wikipedia.org/wiki/L-methylfolate

VITAMIN B12
often provided in diluted form by ingredient manufacturer
often contains hidden ingredients not on finished product label
in "matrix of modified food starch"
matrix = possibly: corn, gluten, lactose, sodium benzoate, sorbic acid
pill may contain 0.1% B12, 99.9% other stuff
pure B12 is ruby red, dilution is pale pale pink
manufacturer may not really know what purchasing people are geting

VITAMIN D
micrograms per dose are thousands of IUs
was a vit d supp in peanut oil for a while: off the market now
often contain lactose, BPA, BHA, sodium benzoate, sorbic acid
looks like and says "pure vitamin D" but powders are diluted
THORNE makes their own vitamin D and it's a pain in the ass

his colleage with master's in nutrit from Bastyr and celiac dz
started taking supp and got rxn
got the "yes we use pure vit D" answer several times
before finding out that it did contain gluten

GOOD MANUFACTURING PRACTICES
cGMPs require testing of ingredients and finished products
ensure consistency, not quality
until recently companies made their own practice standards
then law passed but compliance delayed
now everybody is supposed to be in compliance except for very small companies
small companies have to be in line by next summer
ID content, strength, potency, purity

IN HOUSE LAB
pro: can do in-process testing, quick results, less expensive
con: expensive equipment, perceived conflict of interest
might pass something that should not pass, for the profit
proper equipment:
inductively-coupled plasma
HPLC to ID contents
gas chromatograph-mass spectometer "great machine, closest thing to CSI there is"
microbiology lab
dissolution apparatus to ensure dosage form dissolves
near infrared something spectometry = quick ID method
tell it what you're looking for
stick stainless steel probe into substance and it will tell you if it's there

ASIDE ON MCCAIN BILL
McCain bill in senate to further reg supps
current law is good, has teeth
but FDA hasn't funded or enforced it
lots of play around the edges, "natural viagra", selling drugs as supps
McCain's law backed by anti-doping agency
Miller thinks we should fight it

athletes busted for steroids: this irritates Miller
first thing they say when busted:
"I was taking a supplement, my trainer said it was OK"

"OUT HOUSE" LAB
less perceived conflict of interest
methods: must use right one
standards
quality control

ethics: IBC "miracle" analysis story: questionable-->fraudulent, he and others submitted a product and told lab what it supposedly had in it (biotin, B6, D), then submitted same product claiming different content with new label two more times and got completely different results back each time....so lab wasn't testing they were just playing with the numbers given to them. "They are doing drylabbing"; type up the results that you want, no need for testing.
result: BUSTED: IBC LABS http://www.integratedbiomolecule.com/
biotin is almost impossible to test for and he knew that submitting the request

MAGNESIUM STEARATE and other lubricants
mc other ingredient is magnesium stearate
in supps and drugs
stearic acid with Mg
free flowing slippery/soapy powder
stops clumping and sticking to machinery
make more product more quickly
does nothing for end user
vegetable stearate also showing up
usu animal product, long chain saturated fat, hydrophobic
coats powder products
may inhibit dissolution and bioavailability
product in a gel cap: can dissolve gel cap around it and pellet stays undissolved

edit 6/24/12: MERCOLA thinks Mg Stearate is to be avoided: http://articles.mercola.com/sites/articles/archive/2012/06/23/whole-food-supplement-dangers.aspx?e_cid=20120623_DNL_art_1


lubricants in disguise: ascorbyl palmitate is most common
"fat soluble source of vitamin C" but vitamin C is NOT fat soluble
palmitic acid does same thing as stearic acid

DEMO OF MG STEARATE EFFECT
vinegar (acid) and baking soda (sodium bicarb)
should foam
two glasses of vinegar, breaks 2 capsules into each
first was straight sodium bicarb into vinegar: foamed to top of glass
next use bicarb with 4% magnesium stearate in capsule
break open two caps
doesn't foam, floats on top

BOTANICAL STANDARDIZATION
want to insure same amount of active material in each batch
indina = one of the best in terms of plant extract manufacturers, from Italy
StJW use has crashed over last few years dt research by pharmaceutical corps
scared people but it's one of his favorite botanicals

NEW TECH
liposomes mostly being used for fat soluble nutrients
nanotechnology unproven so far in supps
phytosomes: have decent science, bot extract that reacts with phosphatidyl choline
(usu flavonoids) so bot is on outside

phosphatidylcholine is cell membrane building block
very imp for liver cells, bodies absorb 90% of an oral dose, we want it

generic flavonoid fat soluble, 3 rings, 6 R groups
not well absorbed

silybin is flavonoid from milk thistle
a couple of extra rings
not well absorbed
first flavonoid to be combined with PC
5 times better absorbed when bound with phoscholine

CURCUMIN
curcumin is active ingredient in turmeric
not well absorbed
lipophilic, sparingly water soluble
not really flavonoid but similar
gi and joint protectiive, modulate chol, anti-mets, anti-angiogenesis
modulates cancer genes: NF-kB, AP-1, JNK, others
researched mostly for anti-cancer effect
anti-inflam: downregs cox2, inhibits lipoxygenase and inducible NO synthase
all this via inhib of NF-kB
inhibits prod of TNFalpha, IL 1, 2, 6, 8, 12, and other chemo-attractants
good for CF, diabetes, cancer, nervous and cardio and immuno, and GI dz
antimicrobial
wound healing
animal study of phytosome 5x better absorbed, human study showed 20x+ more better
they're repeating the study because results were too good

Q: curcumin with biopurine
pepper extract
high blood levels dt irritant effect of pepper??
pepper also effect CYP450 enzymes, downregs processing of curcumin?

Q: measurement of absorption usu via blood levels
is this reasonable?
glutathione gets shoved into cells quickly, will not linger in blood
must look at tissue levels
not all research is looking at right part of person with right timing

Q: probiotic question, growth media etc
he's not expert in probiotics
they've stayed away bcs industry is hard to get a grasp on, purity in question
what he's looked at has had impurities of microbial and other content

Q: extracts for glandulars
it's nothing fancy
dessicated ground gland in capsule
not sure about hormone assays, doesn't think they're really doing it
they don't want to know what's in there
don't want to be regulated by FDA as a drug so don't want to label catecholamine content for example
pineal and pituitary glandulars: he's uncomfortable, might contain BSE
BSE = bovine spongiform encephalitis? prion disease?

Q: thyroid conspiracy
Westthroid says manufacturing issue is causing supply problem
he hasn't investigated further

Q: prenatals
definitely know serving size, might be many tablets

dicalcium phosphate used a lot in tablets
he has an exray of tablets in colon from CDC website
**best way to take tabs: chew them up

some food concentrates are yeast based
nutrients added to vat of yeast
then yeast is dessicated and you swallow them

he's not a big fan of tablets esp for elders, pregnant women

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