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Vitamin E, alpha-tocopherol

(and beta-, gamma-, delta-)

Note vitamin E must be taken with food to be absorbed.

Vitamin: E, alpha-tocopherol

VITAMIN C and E : Vitamin C is found not only in plasma but in high millimolar concentrations in cells and tissues.  It is not a pro-oxidant at any dose taken orally.  People with high cholesterol have impaired vascular function, hypertension, and vitamin C can provide significant benefit - doses of 500 mg twice a day lowers blood pressure by 10 points in mild hypertension.  Tea helps too, but probably by a different mechanism.  VC supplement use is associated with lower heart disease and cancer risk, and may reduce inflammation and CRP levels.  Balz Frei, head of LPI, believes the RDA and UL are too low.  Flavanoids from fruits and vegetables are fine, but not nearly as effective as vitamin C at trapping free radicals.  On the JAMA studies on hazards of vitamins C and E, LPI states unequivocally that those reports were interpreted inaccurately by the media.  In fact, many studies have "reported benefits for supplemental vitamins C and E in the prevention and treatment of heart disease and cancer." (Link: Vitamin C: Vitamin E; Source: Linus Pauling Institute Research Newsletter Spring/Summer 2009; added 6/2009)

Daily Value: 30 IU, 20 mg

Hazardous level: safe at more than 10xRDA

Average intake in US diet: 9.8 mg (15.7 iu)

Function: primary signs of deficiency are reproductive failure, muscular dystrophy, and neurological abnormalities. Vitamin E maintains cell membranes; protects vitamin A and essential fatty acids from free radical destruction; lowers risk of cardiovascular disease, cancer, and cataracts, enhances immune function

Details:

FROM LINUS PAULING DIET AND OPTIMAL HEALTH MEETING MAY 18-22, 2005
For those with patience, here are my notes from one of the best professional meetings for M.D. and Ph.D. professionals involved in nutrition professionally. They have not been edited, and are slowly moving on to the appropriate web pages of Nutrition Investigator. Any mistakes are my own, but I have done my best to capture relevant exciting information I learned at this conference.
Simin Meydani - vit E
vit E directly stimulates naïve T cells to divide, increasing immune lifetime; LAT and other signaling molecules are restored to youthful levels
common cold costs $40B annually in US
Maret Traber -
vitamin E traps ROS 1000x faster than lipids
Ascorbyl HNE is another product of free radical protection from vit C and RNS
Stocker -
Native LDL does not affect macrophages or cause plaque
Probucol is a great synthetic antioxidant

Original notes: Vitamin E is the lipid or fat-soluble antioxidant. Like vitamin C, there is overwhelming evidence that vitamin E reduces your risk for a host of different diseases associated with aging, including cancer, heart attacks, atherosclerosis, cataracts, Alzheimer's disease, etc. This has been demonstrated through clinical trials and is based on sound scientific theory and experiments demonstrating reasonable mechanisms by which vitamin E works to prevent these diseases. Vitamin E works in the fat-soluble portion of the body to break free radical chain reactions. It is especially important in low density lipoprotein, which deposits cholesterol in your arteries leading to heart disease. By preventing the oxidation of cholesterol in LDL,

vitamin E prevents the deposition of plaque. Coupled with vitamin C which prevents arterial damage which triggers plaque deposition, the two reduce the risk of heart attack and atherosclerosis on the order of 50% in clinical trials.

Lots of old references with quotations:

Christen, S., Woodall, A.A., Shigenanga, M.K., Southwell-Keely, P.T., Duncan, M.W., and Ames, B. N.

"Gamma-tocopherol traps mutagenic electrophiles such as NOx and complements alpha-tocopherol:

Physiological Implications", PNAS (USA) 94: 3217-3222 (1997)

"Because large doses of dietary alpha-tocopherol displace gamma-tocopherol in plasma and other

tissues, the current wisdom of vitamin E supplementation primarily with alpha-tocopherol should

be reconsidered." "High doses of alpha-tocopherol can increase tumor formation in animals and

displace gamma-tocopherol in plasma and other tissues."

Meydani, S.N., et al. "Vitamin E supplementation and in vivo immune response in health elderly subjects",

JAMA 277: 1380-86 (1997)

"88 free-living, health subjects at least 65... were randomly assigned placebo or 60, 200, or 800 mg/d

of vitamin E for 235 days... Subjects consuming 200 mg/d of vitamin E had a 65% increase in

[immune cells]... No adverse effects were observed with vitamin E supplementation." Study shows

200 mg/d is superior to 800 mg/d

Brown, K.M., Morrice, P.C., and Duthie, G.G. "Erythrocyte vitamin E and plasma ascorbate concentrations

in relation to erythrocyte peroxidation in smokers and nonsmokers: Dose response to vitamin E

supplementation", Am. J. Clin. Nutr. 65: 496-502 (1997) [see also editorial with it, Cross and Traber]

"male nonsmokers (n=50).. during 20 wk of supplementation with 70, 140, 560, and 1050 mg

D-alpha-tocopherol/d. " 560 was better than 1050 mg/d. "in nonsmokers receiving 1050 mg, the

susceptibility to peroxidation also increased. Thus, vitamin E may have prooxidant activity in

nonsmokers at high and prolonged intakes."

Editorial "There is increasing evidence to support the heretic idea that ... tocopherols can have a

prooxidant function, actually accelerating lipid peroxidation processes...the tocopherol radical can

be reduced by ascorbate...this could conceivably explain the decreases in ascorbate with increasing

tocopherol concentrations"

Miwa, K., Miyagi, Y., Igawa, A., Nakagawa, K., and Inoue, H., "Vitamin E Deficiency in Variant Angina",

Circulation 94:14-18 (1996)

"Vitamin E is potent and is the most readily available naturally occurring, lipid-soluble antioxidant

carried in LDL" "Plasma vitamin E levels were significantly lower in patients with active variant

angina...suggesting an association between vitamin E deficiency and coronary artery spasm."

Sano, M. et al, "A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's

Disease", New Eng. J. Med. 336: 1216-1222 (1997)

341 moderate Alzheimer's patients for two years. 2000 IU vitamin E per day. "In patients with

moderately severe impairment from Alzheimer's disease, treatment with ...alpha-tocopherol slows

the progression of disease."

Winklhofer-Roob, B. M., Van't Hof, M.A., and Shmerling, D. H., "Reference values for plasma

concentrations of vitamin E and A and carotenoids in a Swiss population from infancy to adulthood, adjusted

for seasonal influences", Clin. Chem. 43: 146-153 (1997)

Figure 1: ratio of alpha- to gamma- tocopherol is about 20:1

London, R. S., "Newsfront: Vitamin E May Reduce PMS Symptoms", Modern Medicine 51: 15-16 (1986)

"vitamin E may help to relieve the symptoms of premenstrual syndrome... vitamin E significantly

reduced the PMS syndrome of anxiety, headache, cravings, and depression."

Hornbach-Torres, T., "Physicians' Health Study Shows Beta Carotene Supplements to be Without Benefit

or Harm", Press Release, Report on Women's Health Study, Jan. 19, 1996, [617-732-5008]

Aspirin and vitamin E components are continuing on 40,000 female health professionals, age 45 and

older. [This major national trial is being conducted because of the tremendous evidence supporting

the value of aspirin and vitamin E. Personal Health Corporation is monitoring results of this trial,

which is expected to demonstrate clearly the benefits of aspirin and vitamin E in women]. Another

trial is focusing on vitamin E and vitamin C for 8,000 female health professionals at high risk for

cardiovascular disease.

Stephens, N. G., Parsons, A., Schofield, P.M., Kelly, F. Cheeseman, K., Mitchinson, M.J., and Brown, M.J.,

"Randomised Controlled Trial of Vitamin E in Patients with Coronary Disease: Cambridge Heart Antioxidant

Study (CHAOS)", Preventive Medicine 347:781-5 (1996)

2002 patients with atherosclerosis given 800 or 400 IU daily. vitamin E treatment significantly

reduced the risk of the primary trial endpoint of cardiovascular death and non-fatal MI. "We

conclude that in patients with ...atherosclerosis, vitamin E treatment substantially reduces the rate

of non-fatal MI, with beneficial effects apparent after 1 year of treatment.

Diplock, A. T., Machlin, L.J., Packer, L., and Pryor, W.A., Vitamin E: Biochemistry and Health Implications,

New York Academy of Sciences, New York, 1989.

Symposium with scientific basis and medical evidence for effectiveness of vitamin E. Table of

contents shows wide range of evidence and benefits.

Gey, K. F., Puska, P., Jordan, P., and Moser, U.K. , "Inverse Correlation Between Plasma Vitamin E And

Mortality From Ischemic Heart Disease In Cross-Cultural Epidemiology", Am J Clin Nutr 53:326S-34S

(1991)

"in the present study the cross-cultural differences of Ischemic Heart Disease mortality are primarily

attributable to plasma status of vitamin E, which might have protective functions." comparison of

16 European study populations.

P. Knekt, Aromaa, A. Maatela, J., Aaran, R. Nikkari, T., Hakama, M. Hakulinen, T., Peto, R., and Teppo,

L., "Vitamin E and Cancer Prevention", Am J Clin Nutr 53: 283S-6S (1991)

Trial of 36,265 adults in Finland. "Individuals with a low level of vitamin E had about a 1.5-fold

risk of cancer compared with those with a higher level"

Meydani, S.N., Barklund, M.P., Liu, S., Meydani, M., Miller, R.A., Cannon, J.G., Morrow, F.D., Rocklin,

R., and Blumbery, J.B., "Vitamin E Supplementation Enhances Cell-Mediated Immunity In Healthy Elderly

Subjects", Am J Clin Nutr 52: 557-63 (1990)

800 mg E for 30 days with 32 people "short term vitamin E supplementation improves immune

responsiveness in healthy elderly individuals"

Packer, L. , "Protective Role of Vitamin E in Biological Systems", Am J Clin Nutr 53: 1050S-5S ( 1991)

"an adequate intake of vitamin E and the other antioxidants can provide protection from the

increasingly high free-radical concentrations caused by air pollutants and current lifestyle patterns"

"Research has also documented the progressive accumulation of lipofuscin in the aging process in

every animal species studied." This paper documents significant role in prevention of cancer,

atherosclerosis, ischemia, arthritis, cataract,

"Animal research has demonstrated the effectiveness of vitamin E supplementation in inhibiting the

elevation of free-radical concentrations associated with arthritis. In a crossover study on the effects

of vitamin E on osteoarthritis, vitamin E supplementation was significantly more effective than was

placebo in relieving pain. A double-blind study of patients with osteoarthritis also showed that

vitamin E was significantly superior to placebo in regard to pain relief and necessity of additional

analgesic medications and improvement of mobility."

Zaman, Z., Roche, S., Fielden, P., Frost, P.G., Niriella, D.C., and Cayley, A.C.D., "Plasma concentrations

of vitamins A and E and Carotenoids in Alzheimer's Disease", Age and Ageing 21: 91-94 (1992)

In a study of 20 patients over 80 and 20 controls, "both Alzheimer's and multi-infarct dementia

patients had significantly lower levels of vitamin E... than controls"

Tappel, A. L., "Vitamin E as the biological lipid antioxidant", Vitamins and Hormones 20: 493-510.

WHITE PAPER REFERENCES FOR SENIOR FORMULATIONS

Kuklinski, B. and Koepcke, E., "Interaction between vitamin E and selenium under clinical

conditions", pg. 949 in Packer, L. and Fuchs, J., eds. "Vitamin E in health and disease", Marcel

Dekker, Inc., New York, 1993.

Figure 1: Age and serum concentrations

Selenium levels decrease about 10% from age 29-79

vitamin E levels increase- vitamin E levels increase with age, it cannot be ruled out that

the higher values of vitamin E found in elderly are a result of premature death due to deficiency

Kushi, L. H. et al, "Dietary Antioxidant Vitamins and Death from coronary artery disease in

postmenopausal women", NEJM 334: 1156-62 (1996)

- 34,486 women for 7 years. Ave. age - 61 yr old

intake (healthiest quartile)

vit A carotenoids vit E vit C

17,500 IU 11,160 IU 10 mg 194 MG

Healthiest levels among those women taking supplements

vit A , 1-5000 iu; vit E more than 250 iu; vit C, more than 1 g

plasma beta-carotene rises 24-48 hrs after ingestion - vitamin E consumption inversely

associated with risk of death from heart disease in 34,486 post-menopausal women.

Meydani, S.N., et al, "Vitamin E supplementation enhances cell-mediated immunity in healthy

elderly subjects," Am J Clin Nutr 52: 557-63 (1990)

32 subjects over 60, 800 iu vit E for 30 days "Short-term vitamin E supplementation

improves immune responsiveness in health elderly individuals; this effect appears to be

mediated by a decrease in PGE2 and/or other lipid-peroxidation products." - 800 mg for

30 days improves immunity in elderly

Richer, S., "Multicenter ophthalmic and nutritional age-related macular degeneration study", J

Am Optom Assoc 67: 12-29 (1996)

"the ARMD [age-related macular degeneration] population manifested decreased intake

of nutrients vital to cardiovascular health: vitamin E, magnesium, zinc, vitamin B6, and

folic acid."

Watson, R. R. and Leonard, T.K., "Selenium and vitamins A, E, and C: Nutrients with cancer

prevention properties," J. Am. Diet. Ass 86: 505-10 (1986)

Table 1: conservative recommendations for levels of possible

cancer prevention toxicity

A 12,500 25,000

E 200-800 IU safe

C 1,000 mg safe

selenium 50-200 mcg 200 mcg*

*not recommended as safe because of severe toxicity with high doses

- take 200-800 IU to prevent cancer; safe below 1,200 IU

Zhang, ZF, et al "Adenocarcinomas of the esophagus and gastric cardia: the role of diet", Nutr.

Cancer 27: 298-309 (1997)

"Decreased risk...was significantly associated with high ingestion of...niacin, vitamin B6,

iron, and zinc. Higher intakes of vitamin A, beta-carotene, vitamin E, folate, phosphorus, and

potassium were associated with a decreased risk..."- decreased risk of adenocarcinoma with

higher intake of vitamin E, but not statistically significant

Chavance, M. et al, "Vitamin Status, immunity, and infections in an elderly population", Eur J Clin

Nutr 43: 827-835 (1989)

"Two results ...should be underlined. Vitamin B6 status was positively related to percentages

of T-cell subsets" "Vitamin E status was negatively related to the number of past infections:

subjects with a high alpha-tocopherol plasma concentration had fewer infections during the

last 3 years than those with a medium or a low concentration." -elderly subjects with high

vitamin E had fewer infections in past 3 years

Bendich, A., Mallick, R., and Leader, S., "Potential Health Economic Benefits of Vitamin

Supplementation", West J Med 166: 306-312 (1997)

"Nearly $20 billion in hospital charges were potentially avoidable with daily use of folic acid

and zinc-containing multivitamins by all women of childbearing age and daily vitamin E

supplementation by those over 50."- vitamin E (400-800 IU) reduces nonfatal acute

myocardial infarction 77%

D. D. M. Wayner, G. W. Burton, K. U. Ingold, L. R. C. Barclay and S. J. Locke. The relative

contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping

antioxidant in human blood plasma. Biochim. Biophys. Acta, 924, 408 (1987).

B. Frei, R. Stocker and B. N. Ames. Antioxidant defenses and lipid peroxidation in human blood

plasma. Proc. Nat'l. Acad. Sci. USA, 85, 9748-9752 (1988).

V. W. Bowry and R. Stocker. Tocopherol-mediated peroxidation. The prooxidant effect of vitamin

E on the radical-initiated oxidation of human low-density lipoprotein. J. Am. Chem. Soc., 115,

6029-6044 (1993).

V. W. Bowry, K. U. Ingold and R. Stocker. Vitamin E in human low-density lipoprotein - when and

how this antioxidant becomes a pro-oxidant. Biochemical Journal, 288, 341-344 (1992).

K. U. Ingold, V. W. Bowry, R. Stocker and C. Walling. Autoxidation of lipids and antioxidation by

a-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids -

unrecognized consequences of lipid particle size as exemplified by oxidation of human low density

lipoprotein. Proc. Natl. Acad. Sci. USA, 90, 45-49 (1993).

WHITE PAPER REFERENCES FOR STAY WELL FORMULATIONS

There is no evidence of connection with colds, viruses, immune system on a short-term basis.

Note that long term (a year or longer), vitamin E is very important in maintaining the immune

system, and 200 to 400 iu daily significantly enhances immunity (see Meydani article above).

However, on a short term basis, for instance taken only during the week one has a cold, there is

no evidence of value.