Tong Wang, Professor in Lipid Chem and Applications FSHN, Iowa State University Sept 13, 2012...
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Transcript of Tong Wang, Professor in Lipid Chem and Applications FSHN, Iowa State University Sept 13, 2012...
Tong Wang, Professor in Lipid Chem and Applications
FSHN, Iowa State University
Sept 13, 2012
Tocopherols and tocotrienols – structure, function and enrichment in eggs
History of tocopherolsIn 1905, Fletcher found if special factors were removed
from food, disease (Beriberi) occurred
Discovered in 1922 by Evans and Bishop
Supported fertility, thus tocopherol – Greek tokos = childbirth, phero = bring forth, ol = alcohol
In 1936, found abundant in wheat germ oil, in 1938, chemically synthesized
In nature, 8 found to have vitamin E activity: α-, β-, γ- and δ-tocopherol; and α-, β-, γ- and δ-tocotrienol (T-3)
Structure of toco and T-3
,
AR1 = R2 = R3 = Me, α-tocopherolR1 = R3 = Me; R2 = H, β-tocopherolR1 = H; R2 = R3 = Me, γ-tocopherolR1 = R2 = H; R3 = Me, δ-tocopherol
BR1 = R2 = R3 = Me, α-tocotrienolR1 = R3 = Me; R2 = H, β-tocotrienolR1 = H; R2 = R3 = Me, γ-tocotrienolR1 = R2 = H; R3 = Me, δ-tocotrienol
Vitamin E activity and bioavailability
α-tocopherol has the highest bioavailabilitySerum concentration controlled by liver, which preferentially
re-secretes only -toco via the -tocopherol transfer protein (TTP)
Bioavailability of -, -, and - tocotrienol, is 28, 9, 9% (Yap et al 2003)
Activity, IU/mg
Natural -toco 1.49
Synthetic -toco (racemic mix)
1.0
-toco 0.6
-toco 0.3
-toco 0.015
Biosynthesis of tocopherolsExclusively by photosynthetic organisms - in the
chloroplasts
Tocotrienols are the primary form in the seed of monocots (wheat, rice, and barley), palm fruits, GMO corn, not in vegetative tissues
Tocopherols occur in leaves and seeds of dicots
Transgenic expression of the barley enzymes resulted in significant accumulation of T-3 in corn (Pioneer seeds)
Toco concentration of selected oils Tocopherols (ppm) Tocotrienols (T-3, ppm)
Sources alpha beta gamma delta alpha beta gamma delta Total T-3
Total All
Palm Oil 152 - - - 205 - 439 94 738 890 Rice bran 324 18 53 - 236 - 349 - 585 980 Barley 350 50 50 - 670 120 120 - 910 1,360 Oat 180 20 50 50 180 - 30 - 210 510 Wheat Germ 1,179 398 493 118 24 165 - - 189 2,377 Corn 282 54 1,034 54 49 8 161 6 224 1,648 Corn Control 420 26 677 25 189 0 89 5 283 1,430 Corn HGGT 249 28 607 58 664 19 3,512 520 4,715 5,657
Vitamin E function – as antioxidant
Antioxidants protect cells from the damaging effects of free radicalsFree radicals damage cells, contributing to the development
of cardiovascular disease and cancer
Structure-function relationshipIn vitro, antioxidant potential of T-3 > tocoGenerally recognized that > > However, data on the effects of vitamin E on biomarkers of
oxidative stress in vivo are inconsistent
Vitamin E function – not as antioxidant (AOCS Lipid Library)
α-Tocopherol is a gene regulator, causing up-regulation of mRNA or protein synthesis
Vitamin E modulates the activity of several enzymes involved in signal transduction through influencing protein-membrane interactions
Stabilizing the structure of membranes, modulating the immune response
Tocotrienols have been shown properties different from tocosto have neuroprotective effectsto inhibit cholesterol synthesisto reduce the growth of breast cancer cells in
vitro Therapeutic potential for cancer, bone resorption,
diabetes, and cardiovascular and neurological diseases are being actively studied
Vitamin E in cell signaling, gene and metabolic regulation (Shen et al, 2006)
α-Tocopherol strongly inhibits platelet adhesion
γ-Tocopherol exhibits anti-inflammatory functions, not shown by α- tocopherol
Epidemiological data suggests that γ-tocopherol is a better negative risk factor for certain types of cancer
Vitamin E modulates arachidonic acid metabolism – increasing prostacyclin that dilates blood vessels
Functions and mechanism of T-3 (Shen et al, 2006)
Neuroprotective, antioxidant, anti-cancer and cholesterol lowering propertiesT-3 in μM suppresses HMG-CoA reductase, reducing
cholesterol synthesisT-3s are more potent antioxidants than tocos due to their
efficient penetration across membraneAlthough the transport T-3 is low, orally supplemented T-3
results in plasma T-3 of 1 μM, a conc of 10x higher than that required to protect neurons from damage
Nanomolar α-T-3 prevents neurodegeneration by regulating specific mediators of cell death
T-3 but not tocopherol, suppresses growth of human breast cancer cells
Activity of T-3 on breast cancer cells
(Guthrie and Carroll, 1998)
Activity of T-3 on breast cancer cells
Effect of T-3 on protein kinase C (PKC)
Clinical observations - vitamin E on coronary heart diseaseObservational studies associated lower rates of heart disease with r vitamin E
intake - 90,000 nurses had 30% to 40% lower heart disease. Finnish (5,133 followed for 14 years) had decreased mortality
Effects on the heart and blood vessels of healthy women (40,000 ≥45 years, 600 IU for 10 y) - no differences in cardiovascular events or mortality
Randomized clinical trials showed controversial results: The HOPE study (10,000 patients at high risk followed for 4.5 years, 400
IU/day) - no fewer cardiovascular eventsThe HOPE-TOO follow-up study (4,000 participants for another 2.5 years)
- no protection against CHDA men's cardiovascular study (15,000 healthy physicians ≥50 years with
400 IU for 8 y) - no effect on major cardiovascular eventsClinical trials have not provided evidence that vitamin E prevents
cardiovascular disease. More studies in younger and healthier participants taking higher doses is needed
(http://ods.od.nih.gov/FACTSHEETS/VITAMINE.ASP)
Vitamin E on cancer
Link between high intake of vitamin E with a decreased incidence of breast and prostate cancers is inconsistent: A study on breast cancer (18,000 women) - no benefitA study on prostate cancer (29,000 men) - no effectA large clinical trial against prostate cancer (7-12
years of 400 IU E ) – no protection in healthy menAn epidemiologic study showed reduced risk of death
from bladder cancerThe inconsistent and limited evidence precludes any
recommendations about using vitamin E supplements to prevent cancer
Vitamin E on cognitive functionBrain - high oxygen and polyunsaturated fatty acids
Free radical damage neurons, leads to cognitive decline and neurodegenerative diseases
Vitamin E’s protection supported by a clinical trial - 341 Alzheimer patients on 2,000 IU/d for 2 y) - significantly delayed deterioration
Vitamin E consumption - less cognitive decline over 3 y of elderly, (65-102 y)
A clinical trial in healthy older women (600 IU E for 4 years) - no apparent cognitive benefits
769 with cognitive impairment, 2,000 IU/day E - no significant differences in Alzheimer rate
Therefore, most research results do not agree on the use of vitamin E to maintain cognitive performance
Tocopherols and T-3 as antioxidants in bulk corn oil – A comparative study
Oxidative stability of corn oil with elevated T-3 and quantification of oxidation products:
Primary oxidation product:Development of hydroperoxides @ 60oC; Measured as
peroxide value (PV)
Secondary products:Smaller volatile compounds from ROOH cleavage,
measured by conductivity using an OSI Instrument
Dolde and Wang, J Am Oil Chem Soc (2011) 88:1367–1372
Research Q: Will high tocols in corn oil have pro-oxidant effect?
Peroxide Value of Crude Corn Oil at 60OC
0
20
40
60
80
100
120
140
0 1 2 3 4 5 6 7 8 9 10
Day
PV
2005 Control
2005 HGGT
2006 Control
2006 HGGT
R2 = 0.9826
R2 = 0.9972
R2 = 0.9962
R2 = 0.9976
ΔPV/day 2005 2006 Control 11.96 ± 1.06 9.19 ± 0.34 HGGT 9.83 ± 0.32 8.48 ± 0.27
Conclusion: Crude oil from corn expressing tocotrienols at 4,200–5,400 ppm exhibited no prooxidant effects.
Model system study - Toco & T-3 added to purified corn oil
Stripped RBD Corn Oil spiked with:
Toco T-3 Toco T-3 T-3
Concentration (ppm):1002507002,000 5,000
Dolde and Wang, J Am Oil Chem Soc (2011) 88:1759–1765
Research Q: Do tocos and T-3s have different antioxidant activities?
Lipid ROOH formation in corn oil at 60 C with added -tocotrienol
Conclusions of in vitro antioxidant study in bulk oil
Antioxidant properties of tocotrienols (T-3) are similar to those of tocopherols in vitro
At higher concentrations, alpha is a less effective antioxidant than delta and gamma
Alpha tocols propagated primary oxidation at concentrations as low as 700 ppm and pro-oxidant effects were increased with higher concentrations
Carotenoid and T-3 transport efficiency to eggs Walker and Wang, J. Agric. Food Chem. 2012, 60, 1989−1999
• Astaxanthin is a powerful antioxidant:10 x β-carotene; 300 x α-tocopherol
• Tocotrienols are cancer preventative and neuroprotective
Feed enrichment
DietAlgae Biomass
(g/kg)*Palm Extract
(g/kg)**
ppm Expected (relative to egg
oil)A 0 0 0B 4.9 0.12 1,081C 14.7 0.36 3,245D 29.4 0.72 6,490
*Astaxanthin is 1.35% in biomass;**Tocotrienols and tocopherols are 50% in extract
DietFresh Yolk
Cooked Yolk
Day 0 Day 3 Day 6 Day 9 Day 42 Day 40
A
B
C
D
α-Tocotrienol Transfer
Astaxanthin Transfer
Nutrient transfer efficiency
Relative transfer % of α-T-3 to α-toco: 17, 36, and 41% for Diet B, C, D
Conclusion remarks
• Tocopherols represent one of the most fascinating natural compounds that have the potential to influence a broad range of human health and disease;
• The current state of knowledge warrants study of the lesser known forms of vitamin E, i.e. tocotrienols, that have unique biological functions.
Discussion Qs on vitamin E
• Why there are significant disagreements among in vivo and in vitro experiments, and clinical studies– As antioxidants
– On other biological activities
• What type of evidence would you have your dietary recommendation based upon?