Vitamin E, Selenium, on Prostate Cancer

(This article has a duplicate called Selenium, Vitamin E on Prostate Cancer in Cancer on Vitamins section)

The new vitamin criteria recommends a rather low amount for selenium, 50 mcg. or less. This article reveals WHY this is critical.

THE SELECT STUDY

A rather large study testing Vitamin E and Selenium for anti-prostate cancer effects, called the SELECT study, proved to be a major disappointment. ref  So much so that it was stopped after the mid-point analysis. Researchers found that not only did the nutrients fail to show protection against prostate cancer, there was a slight elevation of cancer cases in the vitamin E only group and the selenium group exhibited a slightly elevated diabetes risk.  Another study with same results. Remember before these results there were some reports showing selenium was effective against some cancers. It probably still has value as long as levels are between certain amounts and/or in balance with other related nutrients. 

THE ANALYSIS, Selenium First 

Many scientists assumed the obvious after the results were announced. And that is that Vitamin E and Selenium do not work. But, another group commented on possible explanations for these results. They reported that supplemental selenium appears to offer benefits if your levels are low, but not if you are already in the high range and add more. ref There are now two possible explanations. One is that diabetes changes and upsets protein carrier levels for Selenium, pushing selenium levels up into unhealthy levels for the next explanation. The other is the increased selenium might could increase Glutathione Peroxidase production deactivating free radicals (ROS) which the body needs to turn on the switch for insulin and glucose uptake by cells. ref (selenium, Se, is an anti-oxidant) ref <caution on adjective selection to make it look like big differences but really quite small) ref <**(see summary below) ref  ref  (positive> + ref  ref

NOTE: From the "+ ref" above, copied here is an important message for selenium:  

"The difference between the beneficial effects and the harmful effects of selenium is very narrow," said Dr. Eliseo Guallar of Johns Hopkins University in Baltimore, who has studied the mineral's health effects but was not involved in the new study. "A little bit can be very good, but once you go above a certain level there can be side effects."

The Take Away for Selenium

Increasing levels from dietary food is protective against diabetes risk in a positive upward linear line influence. BUT, supplemental Selenium could push one into a detrimental action area if natural intake levels are already at top end of recommended amounts. ref See Antioxidant load balance.  This is why the new vitamin criteria puts Selenium at such a seemingly low amount, plus it might be wise to occasionally skip consumption days or even weeks if one does not test blood levels. Natural food dietary selenium amounts in the U.S.A. typically fall between 90 to 135 mcg. ref ref

Sidebar: Conclusion from one study listed above, ref, on Selenium and diabetes: CONCLUSIONS—In a probability sample of the U.S. population, high serum selenium levels were positively associated with the prevalence of diabetes. Until findings from prospective studies and randomized controlled trials are available, selenium intake, including selenium supplementation, should not be recommended for primary or secondary diabetes prevention in populations with adequate selenium status such as the U.S. population.

"Selenium as selenomethionine had nearly twice the bioavailability of selenium as selenite." Best not to consume the inorganic forms of sodium selenite and sodium selenate and to limit amounts of other forms Even in pet foods> ref

VITAMIN E in the SELECT study

The SELECT used the SYNTHETIC form of vitamin E. Here is what the results said about the vitamin E side of the SELECT prostate study. The Vitamin E group exhibited a slightly increased prostate cancer rate. In order to fully understand these results, one has to know these few facts about vitamin E: 

1. Vitamin E supplements contain only 1 of 4 tocopherols found in nature and none of the other related four E activity tocotrienol family members. (Alpha, Beta, Delta & Gamma tocotrienols)
2. This one tocohperol form can only be called vitamin E or given vitamin E units, the d'alpha tocopherol, or the synthetic form listed as dl'alpha tocopheryl acetate.
3. Many studies, including the SELECT study, use synthetic dl"alpha tocopheryl which has additional problems of interference in absorption by crowding absorption sites or maybe by crowding out docking sites for the other E family members,(natural E also has this action when isolated and given at higher amounts ).
4. Prostate cells can be attacked by two types of free radicals, oxygen and nitrogen radicals.
5. Alpha tocopherol works against the oxygen radical but not against the nitrogen.
6. It is Gamma tocopherol that works against the nitrogen radical.
7. Taking a high dose of supplemental vitamin E as Alpha tocopherol suppresses the blood levels of natural Gamma tocopherol arriving in food, plus also those of the other tocopherols and all four tocotrienols, and vitamin K.
8. This reduction might compromise the prostate cell protection against nitrogen radicals.
9. Research shows Gamma tocopherol and some of the tocotrienols have greater ability to protect prostate tissue than alpha tocopherol by itself.  
10. The results of the SELECT study are not that unexpected when you know these facts. ref **
11. The SELECT study, initiated largely due to observed facts that higher vitamin E levels equated to less cancers, simply did not consider that many earlier study findings were mainly from food sources which provided lower selenium amounts than tested plus included quantities of all the vitamin E family members as nature puts in foods.  
12. Plus, Vitamin E increased prostate cancer risk only if selenium levels were low. ref
13. There is another aspect that may be working between vitamin E and selenium which could increase advanced prostate cancer risk. ref More research is critically needed here.

SIDEBAR: The preceding points 4, 5 & 6 relate to anti-oxdiant activity. There is a delicate balance needed by the body between anti- and pro- oxidation actions for various metabolic and protective functions. Some studies on Vitamin E do not show a positive result. It could be that the amount of vitamin E used unbalanced the anti-oxidant load. The body has developed ways to harness the reactive nature of free radicals for positive functions which too much vitamin E could disrupt..

For complete nutritional protection, DO NOT SUPPLEMENT WITH high dose FRACTIONATED VITAMIN E as natural d'alpha tocopherol or synthetic dl'alpha tocopheryl etc. You should take some of the other family members too. The proper amounts still need to be determined. It could be 1:1 for gamma and alpha tocopherols, or 2:1. This needs research but is not getting any yet. Three studies using 50, 200, and 400 of alpha tocopherol found the most benefit at just 50 with a slight negative at 400, possibly from interference with the other family E members absorption or enhanced elimination. This could be related to the anti-oxidant activity generated by each amount.

STUDY CONCLUSIONS

** Here is the conclusion from this study: "Statistically significant protective associations for high levels of selenium and alpha-tocopherol were observed only when gamma-tocopherol concentrations were high."  Did you catch that the SELECT study began AFTER this study results were posted that showed gamma tocopherol was needed. DOES THIS MEAN THE SELECT STUDY SET OUT TO FAIL?

SIDEBAR: News about Statin use increasing Diabetes risk. Could this same above mentioned mechanism of too much anti-oxidant activity be at play with Statin use too.  ref  Obviously, statin patients may have heart conditions and be at a higher risk of diabetes even without considering selenium levels.

Summary from ref above: First, they indicate that an optimal degree of ROS production is requisite for normal activation of glucose transport during exercise. Second, they indicate that excessive administration of antioxidants can have deleterious effects on glucose utilization during exercise and possibly glycogen resynthesis during recovery from exercise. This could have negative consequences for skeletal muscle performance.

SELENIUM IN SOIL AND DIABETES

One last research needs to be mentioned to add clarity to these selenium results. The diabetes risk varied for different regions of China. After analyzing for an association, selenium levels showed a connection. In regions where there was a naturally high level of selenium in soil and thus a higher amount in foods grown there, the diabetes rates were higher. ref 

SELENIUM ON CANCER

From the SELECT study, the group that took both Selenium and vitamin E and the selenium only group both exhibited greater advanced prostate cancers. ref Although only the vitamin E group was significant for overall prostate cancer, both the selenium only and selenium and vitamin E groups had increases that were very small and not significant. At 200 mcg, selenium could upset the antioxidant balance when added with dietary amounts. ref Plus, it is also possible that selenium works synergistic to enhance the vitamin E results mentioned below.

But, these last two references should seal the deal. Selenium levels and cancer got off the a fast protective start looking only at levels ingested from food. But research studies using supplements told a different story. Most used 200 mcg. of selenium. Selenium and skin cancer. ref   Remember, selenium is a trace mineral only needed in a rather small range of amounts. There are adverse effects at both too low and too high. Supplements over 50 mcg should NOT be used, period. Especially since few people have blood levels of selenium tested. PLus, it might be precautionary to skip days at even the 50 mcg too.

OF INTEREST FOR FUTURE Analysis: Why prostate cancer often spreads to bone? Looking at PGE2 and Bone factors RANKL and OPG on stimulation of bone building or osteoblastogenesis versus bone tearing down for osteoclastogenesis actions on prostate cancer spreading to bones. ref