Raphael NyarkoteyObu, PhD
I know you will find this work very interesting. This article is taken from my second Doctor of Philosophy (PhD) in Holistic medicine dissertation titled ‘Holistic Medicine in Urology: The Development of Men’s Formula for Prostate Health’ submitted to Universidad Empressarial faculty of Holistic Medicine, Cost Rica. One chapter was dedicated to palm soup and palm oil as a remedy for those with prostatic issues and preventative medicine for men worried about prostate diseases. Palm oil is one of the most abundant natural sources of tocotrienols, with crude palm oil (also referred to as the “tocotrienol-rich fraction”) containing up to 800 mg/kg weight of α- and γ-tocotrienol isotypes. The distribution of vitamin E in palm oil is 30% tocopherols and 70% tocotrienols. Every household in Ghana knows palm soup made from palm fruit. But do you that the palm soup and oil contains abundant of Tocotrienols; a form of vitamin E? Vitamin E is a fat-soluble vitamin that acts as an antioxidant in the body. It’s broken up into two different forms: tocopherols and tocotrienols. A specific form of vitamin E called alpha-tocopherol is the most commonly found form in the modern Western diet.
The study of Vitamin E and prostate cancer is hotly contested. This topic review Vitamin E and prostate cancer. The most important question is whether taking vitamin E increase men risk of prostate cancer? That study was published in the Journal of the American Medical Association (JAMA) about the extended findings of the SELECT trial which stated that vitamin E can increase the risk of prostate cancer, got more people taking about prostate cancer and Vitamin E supplement. However, there are significant things one should know about the study and about vitamin E before taking vitamin E supplements. The facts about vitamin E are:
- There are eight forms of vitamin E, they are not all the same, and evidence to date has shown some forms can help with prevention of prostate cancer.
- The SELECT study used only one form of vitamin E — alpha-tocopherol — which research indicated years before the SELECT trial even began to be ineffective at preventing prostate cancer unless it was used along with another form of vitamin E, gamma-tocopherol.
- The gamma-tocopherol form of vitamin E was shown to be effective at reducing the risk of prostate cancer by researchers at Johns Hopkins School of Public Health before the SELECT trial began.
- Research from 1994 found that alpha-tocopherol robs cells of gamma-tocopherol, which is the form of vitamin E that offers more protection against prostate cancer.
- Limited studies of the tocotrienol forms of vitamin E have indicated they may also offer some protection against prostate cancer.
Therefore, to state that vitamin E increases the risk of prostate cancer without explaining the limitations of the study — including the fact that SELECT used only one form of vitamin E — is a misrepresentation of what scientists and researchers have discovered about vitamin E and prostate cancer to date.
What is vitamin E?
Vitamin E is a complex of eight different isoforms (alpha-, beta-, delta-, and gamma-tocopherol; and alpha-, beta-, delta-, and gamma-tocotrienol) that were discovered decades apart. When vitamin E was first discovered, one fraction seemed to be more potent and necessary for pregnancy, so the scientists named it alpha tocopherol — “tocopherol” from the Greek meaning “to give birth.” Subsequent research, however, revealed that other fractions of vitamin E were also beneficial.
Gamma-tocopherol, for example, was found to have anti-inflammatory and anticancer properties superior to those of alpha-tocopherol. More specifically, research showed gamma-tocopherol, especially in combination with other forms of vitamin E such as delta-tocopherol, prompted cell death in prostate cancer cells, while alpha-tocopherol alone did not have this impact.
The tocotrienols were first isolated in 1965, but their roles in the body were not established until 1980 when researchers reported tocotrienols and tocopherols had an ability to lower cholesterol levels. More recent studies have provided evidence that gamma-tocotrienols may be effective in targeting prostate cancer stem cells and that gamma-tocotrienol and delta-tocotrienol may be better at inhibiting the growth of prostate cancer cell lines than are gamma-tocopherol and delta-tocopherol.
Clearly, the take home message is that there is much more to vitamin E than just alpha-tocopherol, which was the focus of the SELECT study, and that the various forms of vitamin E offer important health benefits, including prevention of prostate cancer.
Alpha-tocopherol vs. gamma-tocopherol
Since alpha-tocopherol and gamma-tocopherol are the two forms of vitamin E we are most concerned with, you may be wondering what the difference is between the two in addition to their differing impact on prostate cancer cells. One difference is their chemical structure, which is similar yet varied enough so they have differing effects on the body. It appears that although the liver breaks down both forms of vitamin E, the body uses a special protein to place more alpha-tocopherol into the bloodstream to go to the tissues than it does gamma-tocopherol. This indicates alpha-tocopherol and gamma-tocopherol have differing roles in the body.
Another difference is their source: although both alpha-tocopherol and gamma-tocopherol are found in certain foods, such as oils (e.g., olive, canola, corn, soybean), almonds, hazelnuts and peanuts, there are significantly higher levels of gamma-tocopherol in corn, canola, and soybean oils (and margarines made with these oils), which are the main oils in the American diet. Therefore, gamma-tocopherol is the main natural dietary source of vitamin E among Americans.
Alpha-tocopherol is the form of vitamin E used in most vitamin E supplements. Supplements that contain alpha-tocopherol may have the form of vitamin E as (1) d-alpha-tocopherol, which is a natural source and so is more bioavailable to the body; or (2) dl-alpha-tocopherol, a synthetic form, which is less bioavailable.
About the SELECT trial
Before exploring the virtues of gamma-tocopherol, it’s important to point out the design of the SELECT trial. SELECT (SELenium and vitamin E Cancer prevention Trial) originally ran from August 2001 through June 2004 and involved 35,000 men assigned to follow one of four different interventions per day: 200 micrograms (mcg) of L-selenomethione (selenium) plus a vitamin E placebo; 400 IU vitamin E (as alpha-tocopherol) plus a selenium placebo; 200 mcg selenium plus 400 IU vitamin E; or placebo of both.
The researchers ended the trial early because the participants were not displaying any benefits from taking selenium or vitamin E, either alone or combined. In fact, the investigators reported there was a slight increase in prostate cancer among men who took vitamin E only and a slight increase in diabetes among men who took selenium alone.
The original SELECT was planned to include at least a seven-year follow-up period, and this is where the results of the new JAMA study enter the picture. Authors of the study report that healthy men with an average risk of prostate cancer who took 400 IU vitamin E during SELECT demonstrated a significantly increased risk (17 percent) of prostate cancer when compared with men who took placebo.
Gamma-tocopherol and prostate cancer
Saying that vitamin E increases the risk of prostate cancer is like saying all cars get 25 miles per gallon: some types of cars get better mileage, some get worse. Some forms of vitamin E offer better anticancer benefits than others. This is true when it comes to alpha-tocopherol and gamma-tocopherol.
Let’s return to the Johns Hopkins study mentioned earlier. A total of 10,456 men participated in the trial, in which researchers compared alpha-tocopherol, gamma-tocopherol, and selenium. They found that men who had the highest blood levels of gamma-tocopherol were five times less likely to get prostate cancer. Another important finding was that alpha-tocopherol and selenium protected against prostate cancer only when gamma-tocopherol intake was high. That means the alpha- and gamma-tocopherols have a synergistic effect when it comes to prostate cancer.
Then there was a review published in “Carcinogenesis” in 2010 in which the authors explained how many large-scale studies with alpha-tocopherol had not shown anticancer benefits. The authors suggested this lack of effect was caused by high doses of alpha-tocopherol, which reduced the body’s levels of delta-tocopherols. They also noted that gamma-tocopherol had “strong anti-inflammatory” properties and that it “may be the more effective form of vitamin E in cancer prevention.” They concluded by saying, “we propose that a gamma-tocopherol-rich mixture of tocopherols is a very promising cancer-preventive agent and warrants extensive future research.”
Yet another study indicated that gamma-tocopherol can help protect against development of prostate cancer. From a total of approximately 20,000 men who donated blood samples for analysis of micronutrients and prostate cancer risk, the investigators found “potential chemopreventive effects of gamma-tocopherol on prostate cancer” and a weak association between alpha-tocopherol and prostate cancer risk.
Gamma-tocopherol: The other vitamin E
When you shop for vitamin E supplements, in most cases you will see “alpha-tocopherol” on the ingredient label. Alpha-tocopherol is also the form of vitamin E that is most often used in clinical studies. Given what scientists have discovered thus far about alpha-tocopherol and gamma-tocopherol, however, men should look to choose a mixed tocopherols vitamin E supplement that includes alpha- and gamma-tocopherols, and the reason is simple:
Alpha- and gamma-tocopherols work together: the alpha form inhibits the production of cell-damaging free radicals, while the gamma form captures and neutralizes them. If the level of alpha-tocopherol gets too high in the body, it tries to eliminate gamma-tocopherol in the cells. Therefore, both forms of vitamin E have to be kept in relative balance.
So before you throw away your vitamin E supplement based on the nightly news report, check the label. Chances are it contains alpha-tocopherol alone; if so, look for a brand that contains mixed tocopherols which includes alpha-tocopherol and gamma-tocopherol with a high gamma relative balance. Because among the facts about vitamin E is one that says some forms can help prevent prostate cancer.
Vitamin E is composed of two structurally similar compounds: tocopherols (TPs) and tocotrienols (T3). Despite being overshadowed by TP over the past few decades, T3 is now considered to be a promising anticancer agent due to its potent effects against a wide range of cancers. A growing body of evidence suggests that in addition to its antioxidative and pro-apoptotic functions, T3 possesses a number of anticancer properties that make it superior to TP. These include the inhibition of epithelial-to-mesenchymal transitions, the suppression of vascular endothelial growth factor tumor angiogenic pathway and the induction of antitumor immunity. More recently, T3, but not TP, has been shown to have chemosensitization and anti-cancer stem cell effects, further demonstrating the potential of T3 as an effective anticancer therapeutic agent. With most of the previous clinical studies on TP producing disappointing results, research has now focused on testing T3 as the next generation vitamin E for chemoprevention and cancer treatment
According to a study by Barve et al 2010, the biological activities of tocotrienols are receiving increasing attention. The study report the efficacy of a mixed-tocotrienol diet against prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate (TRAMP) mouse model. A 2007 study by Muenyi found that both gamma- and delta-tocotrienols induced time and concentration dependent growth inhibition and programmed cell dead (apoptosis) in LNCaP cells.
The natural vitamin E family includes 8 chemically distinct molecules: α-, β-, γ-, and δ-tocopherol and α-, β-, γ-, and δ-tocotrienol. Structurally, vitamin E consists of a chroman ring with either a saturated side chain (tocopherols) or an unsaturated side chain (tocotrienols). Isoforms of tocotrienol differ from each other based on the methyl groups on the chroman ring (Fig. 1). For chemoprevention research, α-tocopherol is among the most studied components of vitamin E( Wen et al 2007, Ni et al 2005)
A 2012 review by Ling et al revealed that T3, especially the gamma and delta isoforms, exhibits superior anticancer effects in comparison with TP, which include anti-inflammation, anti-invasion etc.A similar 2019 review by Tham et al puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells.
Another 2019 study by Tang et al highlighted the therapeutic potential of using γ-T3 in combination with a Tie-2 inhibitor to treat advanced prostate cancer.
Another 2019 study by Aggarwal et al found that Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. This current study detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks
A 2018 study by Kaneko et al results suggest that δ-T3 could inhibit the survival of prostate cancer stem-like cells under hypoxia, primarily through the inactivation of HIF-1α signaling.
Vitamin E is sometimes used to lessen the harmful effects of medical treatments, such as radiation and dialysis for treating cancer. This is because it’s a powerful antioxidant that fights off free radicals in the body. It’s also used to reduce unwanted side effects of drugs that may cause hair loss or lung damage.
Certain isomers of vitamin E have also been tied to cancer protection. Several animal studies have found evidence of suppression of tumor growth using oral doses of tocotrienols. While there’s more to learn about how exactly this works, several mechanisms of action are thought to be by tocotrienols, inducing cancer cell death, turning off genes tied to cancer and inhibiting angiogenesis, or the abnormal growth of blood vessels inside a tumor. In animal studies, cancer-protective abilities have been demonstrated in cases of breast, prostate, hepatic and skin cancers.
Fig 1. Structure of the different analogs of tocotrienols.
Different Forms of Vitamin E
There are eight major isomers of vitamin E. Most of the health benefits of vitamin E described above come from studies involving only form of vitamin E called alpha-tocopherol, which is only one of eight forms. Recently, researchers have focused more attention on other forms of vitamin E as well, with particular focus on tocotrienol, which some consider the “the 21st century vitamin E.” (9) Alpha- and beta-tocotrienols have been found to be the least active forms overall, while delta- and gamma-tocotrienols are the most active. Recent findings suggest that it’s not that alpha-tocopherol is harmful, but it may interfere with absorption of other forms of vitamin E, including other tocopherols and tocotrienols that are needed for heart and cognitive health.
According to the Linus Pauling Institute at Oregon State University:
Vitamin E is actually composed of two structurally similar compounds, tocopherols and tocotrienols. Each compound is comprised of four components, each of which has distinct molecular structures. Each component is referred to as an isomer (or vitamer) of vitamin E. Each isomer of vitamin E has unique properties, health benefits, characteristics, and attributes, with important applications when formulating food or beverage products.
Given the benefits of different vitamin E isomers that have been discovered, today there’s a push to rethink the way that vitamin E is labeled and described in research studies. When only form of vitamin E is studied (usually only the isomer alpha-tocopherol), many believe that any benefits revealed from the study should not be attributed to “vitamin E” given that without the other isomers it’s not actually vitamin E in its full form that’s being studied. Steps are also being taken to educate the public about benefits specifically associated with tocotrienols isomers, which include protection against a wide range of common, chronic diseases due to having unique antioxidant and anti-inflammatory potential. Tocotrienols have also been found to have anticancer and anti-tumor abilities, lipid and cholesterol-lowering effects, and protective effects that impact the brain, neurons, cells and immune system.
So what does all of this mean regarding the types of vitamin E in your diet? It’s best to get a variety of vitamin E isomers from your diet, given that different types have different benefits. Tocotrienols have proved to contain some exceptional benefits that are not shared by other forms. Today, the brightest spot for tocotrienol research is in chronic conditions, such as cardiovascular disease, metabolic syndrome, cancer and osteopenia/osteoporosis. Sources of tocotrienols are not as widely available or popular in most people’s diets however. These include annatto seed, coconut, barley, or commercially extracted palm oil and rice bran oil.
Finally, it’s also best to obtain vitamin E naturally from foods, rather than getting synthetic vitamin E from low-quality supplements or processed foods, which is usually in the form of either gamma-tocopherol or alpha-tocopherol. The vast majority of synthetic vitamin E found in supplements is not the type that’s actually found in nature and not necessarily helpful for preventing disease and boosting health. That’s why the best way to get vitamin E benefits is by consuming natural vitamin E foods.
How to Get Enough of the Different Vitamin E Isomers (Including Tocotrienols):
Most food sources in the typical person’s diet are high in vitamin E isomers like gamma-tocopherol and to a lesser degree alpha-tocopherol. This is especially true of oils derived from major crops like soybean, corn, cottonseed and sesame seed, which provide about 80 percent of the vitamin E isomers most people in the U.S. get from their diets. These oils contain between three to five times as much gamma-tocopherol compared alpha.
Vitamin E Side Effects
Vitamin E benefits most healthy people when taken by mouth or applied directly to the skin. Most people do not experience any side effects when taking the recommended dose, but in high doses there are adverse reactions that have been recorded. Vitamin E may be unsafe when taken in very high amounts, especially for people who have conditions such as heart disease or diabetes. If you suffer from these health issues, do not take doses of 400 IU/day or more.
Some studies show that taking high doses of vitamin E, which is between 300–800 IU each day, might increase the chance of having a serious stroke called hemorrhagic stroke by 22 percent. One serious side effect of too much vitamin E is an increased risk of bleeding, especially in the brain.
Avoid taking supplements containing vitamin E or any other antioxidant vitamins immediately before and following angioplasty, a type of heart procedure. These vitamins seem to interfere with proper healing, so speak to your health care professional if you’re undergoing this kind of procedure and taking any supplements/vitamins.
Supplementing with very high levels of vitamin E could potentially lead to the following health concerns:
- heart failure in people with diabetes
- worsening bleeding disorders
- increasing the chances that head, neck and prostate cancer will return
- increasing bleeding during and after surgery
- increasing chance of death after a heart attack or stroke
One study found that vitamin E supplements can also be harmful to women who are in the early stages of pregnancy. Women who took vitamin E supplements during their first eight weeks of pregnancy showed an increase of congenital heart defects. High doses of vitamin E can also sometimes lead to nausea, diarrhea, stomach cramps, fatigue, weakness, headache, blurred vision, rash, bruising and bleeding. Topical vitamin E can irritate some people’s skin, so try a small amount first and make sure you don’t have a sensitivity.
Relationship with Other Nutrients and Interactions
Vitamin E supplements can slow down blood clotting, and when you use medications that also slow clotting, you may increase the chances of bruising and bleeding. Some medications that slow blood clotting include aspirin, clopidogrel, ibuprofen and warfarin. Warfarin (Coumadin), in particular, is used to slow blood clotting. Taking vitamin E with warfarin can increase your chances of bruising and bleeding, so be sure to have your blood checked regularly in order to regulate your dosing.
Medications that are used for lowering cholesterol may also interact with vitamin E. It’s not known if taking vitamin E alone decreases the effectiveness of some cholesterol-lowering medications, but it does seem to affect cholesterol when taken with beta-carotene, vitamin C and selenium.
- Vitamin E benefits the body by playing the role of an antioxidant. As a fat-soluble vitamin, its benefits include its role in proper function of many organs, enzymatic activities and neurological processes.
- Vitamin E is a collective description for eight compounds, four tocopherols and four tocotrienols, and they provide different benefits. It’s best to get a variety of vitamin E isomers from your diet, given that different types have different benefits.
- Vitamin E benefits include balancing cholesterol, fighting free radicals, preventing disease development, repairing damaged skin, thickening hair, balancing hormones, helping PMS symptoms, improving vision, helping people with Alzheimer’s, potentially lowering cancer risk and improving effects of medical treatments, and boosting physical endurance and muscle strength.
- It is found only in plant foods, including certain oils, nuts, grains, fruits and wheat germ. It’s also available as a supplement. Some of the top vitamin E foods you can eat to get these vitamin E benefits include sunflower seeds, almonds, hazelnuts, wheat germ, mango, avocado, butternut squash, broccoli, spinach, kiwi and tomato.
- Vitamin E benefits the mother and child during pregnancy as well, as it’s a vital vitamin for growth and development.
- Vitamin E deficiency symptoms include include loss of muscle coordination and impaired vision and speech.
- Palm soup and oil contains abundant of Tocotrienols for your health in general.
Disclaimer: As pertains to all my previous articles, they are for educational purposes and not to be use as substitute to medical advice.
Dr. Raphael NyarkoteyObu, PhD, Is an honorary Professor of Naturopathic Medicine with research interest in Naturopathic & Holistic Urology, Vinnytsia State Pedagogical University, Ukraine. President of Nyarkotey College of Holistic Medicine- Formulated of FDA approved Men’s Formula for Prostate Health, Women’s Formula for wellness &Nyarkotey Tea for cardiovascular Health. 0241083423 or 0541234556