Tag: vitamin E

Vitamin E – the good and the bad

Admin

December 10. 2024

Vitamin E is a large family of active substances, with alpha-tocopherol being the most well-known and used, but it has good and bad relatives.

Atherosclerosis and cardiovascular disease are some of the most common causes of death worldwide, and also reduce the quality of life for millions of people. The authors of a new article have reviewed the recent scientific evidence on the effects of increased intake of the two main forms of vitamin E, tocotrienols and tocopherols, on patients with atherosclerosis and the cardiovascular diseases that accompany atherosclerosis (Rafique et al., 2024).

The article has focused on the fact that vitamin E is much more than the commonly known alpha-tocopherol, and that some of the other forms of vitamin E in the diet may contribute to better protection of the body’s cardiovascular system.

An attempt to illustrate the structure of vitamin E can be seen below, where the four tocotrienols are on the left with three double bonds in the long carbon chain, and the four tocopherols are on the right.

Tocotrienols                                                                  Tocopherols

Figure 1: The eight substances that naturally belong to the vitamin E group in plants. The tocotrienols are on the left, and the tocopherols on the right. Alpha-tocopherol is shown in red. The arrows in the figure show how trienols can be converted to alpha-tocopherol in our body. (Figure modified from Querchi et al. (2015)).

The new article is based on a review of 5 studies published in the 8 years from 2015-2022, which examined the effect of tocotrienol or tocopherol supplementation on the development of atherosclerosis or patients with already existing atherosclerosis and other cardiovascular diseases.

A study highlighted in the recently published article showed that tocotrienol at a dose of 250 mg per day for 16 weeks had a clear positive effect on reducing cholesterol and reducing important biomarkers of oxidative stress and inflammation in the body (Querishi et al 2015):

  • C-reactive protein (CRP): a 40% decrease

CRP is produced in the liver and is a frequently used marker for inflammation in the body in general and also for atherosclerosis, where a lower level gives patients a lower risk of having a blood clot.

  • Malondialdehyde (MDA): a decrease of 34%

Malondialdehyde is produced in the body’s tissues and high levels are a sign of oxidative stress and low antioxidant levels.

  • Gamma-glutamyl transferase (GGT): a decrease of 22%

High GGT levels in the blood are a sign of strain on the liver-biliary system and pancreas.

Along with the above positive changes, the total antioxidant status in the blood was increased by 22%, and cytokines that promote inflammation, such as interleukins (IL-1, IL-12), were reduced by 15-17%. Tocotrienol also had a positive effect on several types of micro-RNA, which are important in the regulation of inflammation and fatty acid metabolism.

Overall, the article showed that tocotrienol can help reduce the processes in the body that lead to atherosclerosis – especially in patients with already existing symptoms of cardiovascular problems.

However, the positive studies on tocotrienols mentioned in the new article are all of shorter duration – 3–6 months. In contrast, the studies the article compares with were all conducted with alpha-tocopherol, and of duration as long as 30 years.

These long-term studies of alpha-tocopherol have shown results with considerable variation. A Finnish study (Huang et al 2019), which followed 29,000 male smokers for 30 years, showed that a better diet with an approximately 30% higher content of natural alpha-tocopherol, initially reduced mortality by 22%, including atherosclerosis by 10-21%, heart attack by 2-17% and cerebral hemorrhage by 22-38%. A supplement of 50 mg/day RL alpha-tocopherol for approximately 6 years within the 30-year period, on the other hand, did not affect symptoms or mortality in the short or long term.

Another long-term American study followed 3,780 healthy women for 11 years, measuring the effect of an alpha-tocopherol supplement to double the level of alpha-tocopherol in the blood. The women were aged between 50 and 79 at the start of the study. The study found an 8% reduced incidence of cerebral hemorrhage with higher levels of alpha-tocopherol in the blood, but an increased incidence of other cardiovascular diseases, such that the overall incidence of cardiovascular problems increased by 8%.

Chemically produced “vitamin E”
Since vitamin E is a strong antioxidant that is known to reduce the unwanted oxidation of LDL cholesterol and other fats in the walls of cells, thereby counteracting atherosclerosis, etc. (Belcher et al 1993), it is relevant to ask why large and long-term studies do not unequivocally show that a supplement of vitamin E is super good.

One explanation could be that we somehow need free radicals, and that vitamin E, with its antioxidant effect, therefore removes something “good.” A more credible explanation, in my perspective, is that large-scale experiments have often used a cheap and poor form of chemically produced vitamin E.

When people talk about there being 8 forms of vitamin E, they are often referring to the 8 different molecules shown above (Figure 1). However, alpha-tocopherol is a complex molecule, and in three places in the molecule a carbon atom is linked to four other atoms/molecules. In the figure below, the positions of the three carbon atoms are marked with red stars (Figure 2).

Figure 2: Drawing of the molecular structure of alpha-tocopherol, where the stars mark the three places where a carbon has four different bonds. (Figure modified from Kohlmeier (2015)).

When you look at the drawing, you can easily imagine that the different molecules can rotate freely, but in reality they are very stable. If hydrogen (H) and the methyl molecule (CH3) are in just one of the places opposite to what is shown in the drawing – yes – then biologically you have seen a different molecule.

Unfortunately, this is exactly what happens when you produce vitamin E the old-fashioned chemical way. That is, atoms and molecules turn randomly, which means that they have two possible positions in three different places.

Therefore, 2 different x 2 different x 2 different = a total of 8 different forms of the molecule are chemically produced – see Figure 3 below. Of these, only one form is the natural form of vitamin E, which is found in plants and therefore in our diet, while the other seven versions of the molecule are unknown to plants and animals.

In particular, the four forms shown on the right in the figure below are broken down relatively quickly in the liver like other foreign substances. However, we know very little about what toxic effects they have before they are broken down, and what long-term toxic effects arise due to the more or less broken down substances.

Figure 3: Graphic illustration of the eight forms of vitamin E that are created when attempting to produce vitamin E using simple chemical methods. The natural alpha-tocopherol is marked in red. (Figure modified from Kohlmeier (2015)).

When you want to produce cheap supplements, such as cheap multivitamin pills, you often use chemically produced vitamin E. In these cheap products, the mixture of the eight forms of vitamin E is called rac alpha-tocopherol or DL ​​alpha-tocopherol. The natural alpha-tocopherol has been given first names such as D alpha-tocopherol or RRR alpha-tocopherol.

To increase the shelf life of various foods, vitamin E is often used as an antioxidant during production. Since the focus is on vitamin E’s antioxidant effect and not its effect as a vitamin, many manufacturers prefer to use the cheapest form of vitamin E, which is the chemically produced form that contains all 8 forms in equal amounts.

Figure 4 below graphically shows how the eight natural forms of vitamin E should be understood, compared to the seven additional forms that arise when alpha-tocopherol is produced chemically.

It can be seen that the variation in natural vitamin E is due to variation in the ring shown on the left, while the variation in chemically produced alpha-tocopherols is due to changes in the long chain extending from the rings.

Figure 4: At the top, the eight forms of vitamin E found in plants, and therefore naturally present in our diet, and then the eight forms of alpha-tocopherol – one natural and the other seven forms resulting from the chemical production of alpha-tocopherol, which are therefore also present in our diet when “vitamin E” is used as an antioxidant and in cheap dietary supplements. (The figure is modified from Kohlmeier (2015) and Querchi et al. (2015)).

Conclusion
It is now well documented that the different forms of vitamin E, in addition to their common effect as antioxidants, have quite different mechanisms of action in the body. The different natural forms of vitamin E contribute with different mechanisms to protect the body’s cardiovascular system, the central nervous system and also provide some protective effect against certain forms of cancer.

The chemical production of alpha-tocopherol, on the other hand, casts a shadow over the results achieved with long-term supplementation of alpha-tocopherol, so that it is not possible to determine whether a daily supplement of this vitamin E contributes to a healthy and long life or perhaps has negative effects.

Tocotrienols are always extracted from natural sources, and existing studies show that they have a safe effect even at relatively high daily intakes. It is therefore advantageous to choose a vitamin E with a high content of tocotrienols.

Klaus K. Sall
Biologist, Cand. Scient.
Sall&Sall Counseling

Notes

EFSA: The European Food Safety Authority EFSA estimates that a daily adequate intake of vitamin E measured as alpha tocopherol is 13 mg/day for men and 11 mg/day for women (EFSA 2015). In 2024, EFSA estimated that the highest daily intake for adults is 300 mg D alpha-tocopherol (EFSA 2024). In a previous specific case, EFSA estimated that a daily intake of 1000 mg mixed tocotrienols and tocopherols does not pose risks. (EFSA 2008).

Chirality: The eight forms of alpha-tocopherol that are formed during chemical production – are part of a phenomenon called chiral molecules. I have created a website that describes the importance of this phenomenon for all life (text in Danish): www.kiral.dk.

Mix: Studies have shown that alpha-tocopherol suppresses the body’s use of tocotrienols. Therefore, in supplements containing both alpha-tocopherol and tocotrienols, the tocopherols will be primarily utilized (Querishi et al 2015).

12: A total of 12 natural molecules have been found that have vitamin E effects. Four of them rarely occur in human food and are not known in dietary supplements.

Organic farming: In organic foods, it is not permitted to use the unnatural forms of alpha-tocopherol.

References and further reading

Belcher, J.D. et al. (1993) ‘Vitamin E, LDL, and endothelium. Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro.’, Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 13(12), pp. 1779–1789. Available at: LINK.

EFSA (2008) ‘Opinion on mixed tocopherols, tocotrienol tocopherol and tocotrienols as sources for vitamin E added as a nutritional substance in food supplements, EFSA Journal, 6(3), p. 640. Available at: https://doi.org/10.2903/j.efsa.2008.640.

EFSA (2015) ‘Scientific Opinion on Dietary Reference Values for vitamin E as α-tocopherol’, EFSA Journal, 13(7), p. 4149. Available at: https://doi.org/10.2903/j.efsa.2015.4149.

EFSA (2024) ‘Scientific opinion on the tolerable upper intake level for vitamin E’, EFSA Journal, 22(8), p. e8953. Available at: https://doi.org/10.2903/j.efsa.2024.8953.

Huang, J. et al. (2019) ‘Relationship Between Serum Alpha-Tocopherol and Overall and Cause-Specific Mortality’, Circulation Research, 125(1), pp. 29–40. Available at: LINK.

Kohlmeier, M. (2015) Fat-Soluble Vitamins and Nonnutrients: Vitamin E, in: Nutrient Metabolism: Structures, Functions, and Genes, pp. 514–525. Elsevier. Available at: LINK.

Qureshi et al. (2015) ‘Pharmacokinetics and Bioavailability of Annatto δ-tocotrienol in Healthy Fed Subjects’, Journal of Clinical & Experimental Cardiology, 6(11). Available at: LINK.

Rafique, S. et al. (2024) ‘Comparative efficacy of tocotrienol and tocopherol (vitamin E) on atherosclerotic cardiovascular diseases in humans’, Journal of the Pakistan Medical Association, 74(6), pp. 1124–1129. Available at: https://doi.org/10.47391/JPMA.9227.

Sen, C. et al. (2000) ‘Molecular basis of Vitamin E action – Tocotrienol potently inhibits glutamate-induced pp60(c-Src) kinase activation and death of HT4 neuronal cells’, The Journal of biological chemistry, 275, pp. 13049–55. Available at: https://doi.org/10.1074/jbc.275.17.13049.

Sen, C.K. et al. (2007) ‘Tocotrienols: The Emerging Face of Natural Vitamin E’, Vitamins and hormones, 76, p. 203. Available at: https://doi.org/10.1016/S0083-6729(07)76008-9.

Healthy and Safe

Robert Verkerk

October 25, 2007

There are over 480,000 published peer-reviewed research studies on food supplements or ingredients used in food supplements, and the vast majority of these show positive effects. There are only a small handful of studies that have shown negative effects, these generally being associated with high doses or synthetic forms of ingredients like vitamin A, beta-carotene and vitamin E.

In the case of vitamin A, there is no doubt that high doses of this fat soluble vitamin can be harmful and an upper safe level or maximum permitted level for this vitamin makes perfect sense.

There are three key studies showing negative effects of beta-carotene on diseased or high-risk patients, but these have all used synthetic beta-carotene, in the absence of natural carotenoid complexes found in natural carotenoid-rich fruits and vegetables which have been found to be potent cancer-fighting nutrients. Ironically, these natural ‘mixed carotenoids’ are disallowed by the Food Supplements Directive.

Finally, there are four key negative studies on vitamin E, all of them conducted with synthetic vitamin E, which comprises only one of the eight vitamin E forms found in nature, but in its esterified form. This form, alpha-tocopherol, the only vitamin E form allowed by the Directive, actually reduces the body’s absorption of gamma-tocopherol which is the key antioxidant form of vitamin E found in food sources.

By: Robert Verkerk, The Alliance for Natural Health, United Kingdom

New slander against antioxidants

Niels Hertz

March 13, 2007

A new article maintains that antioxidants cause death, but the article is based on a comparison of results from incomparable studies.

Once again a scientific article has created a commotion regarding antioxidants. It claims that they cause death. This has been heard, and disproved, before. Because of the common uncertainty regarding this subject, we are nonetheless forced to take a stand regarding this claim.

The man behind this claim is a Serbian professor from a university located in the town of Nis. One of the co-authors is a Danish physician who has, among other things, declared antioxidants to be poisonous and cancer causing on Danish TV. He even suggested that they are poisonous in the amounts found in vegetables.

The study is a so called Meta analysis. It combines as many old studies on antioxidants as possible and extracts a kind of average from their results. Small four week studies are blended up with larger studies which have gone on for up to 12 years. Studies where very small doses were used are blended up with studies on mega doses, studies using one antioxidant are blended up with studies on combinations of antioxidants (e.g. vitamin E, vitamin C, and selenium), and so on. Among the studies used, there are at least eight different combination treatments using vitamin E. This enormous mess alone causes the study to be somewhat questionable. One cannot calculate an average between apples and oranges.

This is not even the worst part. In an attempt to prove that vitamin E increases risk of death (the articles primary claim), the ignored studies where selenium was used together with vitamin E. The selenium studies often showed reduced mortality and lowered cancer risk. This was not good for the Meta analysis authors, it disturbed their theory. They eliminated 11 essential studies on vitamin E and selenium from the analysis.

Selenium was ignored, but that wasn’t enough. The still couldn’t prove that vitamin E is harmful. The numbers wouldn’t work. To solve this, the article uses the fact that the antioxidant beta-carotene, the yellow colouring in carrots, increases death rates in smokers. This is commonly accepted (although not completely certain). In two of the largest studies conducted on antioxidants, a very slightly increased death rate was found due to a combination of beta-carotene and vitamin E.

More peculiarities
Common sense lends to the conclusion that beta-carotene is the villain in these studies. This was known in advance. Combinations of vitamin E with e.g. vitamin C and/or selenium do not increase mortality. More likely the opposite is true. In the large and very thorough French SU.VI.MAX study, death rates in men fell by over a third when they received vitamin E and vitamin C as well as selenium (besides zinc and beta-carotene!). This introduced a new era because this was the first time in our part of the world that a large array of antioxidants was used in study; which is what most people recommend. The antioxidants in our food are an orchestra, not solo instruments. They must play together to work. In a Chinese study from Linxian the same thing was found: lower mortality after supplements of vitamins E and C, selenium, beta-carotene, and vitamin A.

But the article in question maintains that vitamin E causes death. The claim is built, along with the discussed “manoeuvres,” on the two aforementioned studies, because the other vitamin E studies are insignificantly small in comparison. In these studies vitamin E was used with beta-carotene, and vitamin E was blamed in the Meta analysis for the poor results.

This is like claiming that mineral water is deadly if someone dies after drinking water mixed with arsenic. This conclusion is insane. The arsenic is deadly, not the water. Even though A+B is dangerous, it can naturally not be claimed that both A and B are dangerous alone.

There are other peculiarities in the article. Among other things, in at least two of the studies used, mortality was calculated many years after the end of the study. This is comparable to blaming a traffic accident for back pain when the pain became apparent eight years after the traffic accident. This type of measure was apparently necessary to get the desired results.

It is very easy to make these arguments in a scientific journal. If not for the press, it would be ignored. The article is based on a comparison of a number of incomparable articles, and this makes it hardly worth the effort it takes to make it better. It has also been exposed to sharp criticism. It has been clearly dismissed by two unrelated statisticians and by a professor of nutrition at Harvard University, Meir Stampfer. Stampfer is world renown and among the leading figures in nutrition studies encompassing over 300,000 people. He says that he will continue taking his vitamin supplements, unfazed by the article. But he adds that the article can lead to misinterpretation of the information that we have.

This is unfortunately an all too real possibility. Not in the least because the analysis’s authors insistently do the same.

By: Niels Hertz MD

 

References
1. Bjelakovic G, Nikolova D, Gluud LL et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention trials. JAMA 2007;297:842-857.
2. Virtamo J et al. ATBC Study Group. Incidence of cancer and mortality following alpha-tocoferol and beta carotene supplementation: A postintervention follow up. JAMA 2003;290:476-485.
3. Lee IM et al. Vitamin E in the primary prevention of cardiovascular disease and cancer. The Women’s Health Study. A randomized, controlled trial. JAMA 2005;294:56-65.

jama.ama-assn.org

Again, uneasiness regarding the pill

Claus Hancke

July 31, 2006

The pill (contraception in pill form) drains the body of the antioxidants, vitamin E and Q10. This could mean that a supplement would make it much safer to take the pill.

More than 100 million women worldwide use the pill as contraception. The pill is believed to be remarkably safe, and it is easy to forget that it can have serious side effects. According to a Dutch report from 2003, users of the pill have a 3-6 times higher risk of developing blood clots in the veins, which is a dangerous condition. In addition, they have a 2-5 times higher risk of developing blood clots in the heart or of suffering from stroke. These numbers are the same for the modern forms of the pill, which have few other few side effects.

If the risk of disease is low, (because of being young and otherwise healthy) than a low percentage increased in risk does not so important. But why is there any increase at all? Light has been thrown on this question by researchers of the Albert Einstein College of Medicine in New York. They have proven that users of the pill have lower vitamin E and Q10 levels in their blood than women who do not take the pill. Vitamin E and Q10 are well known antioxidants.

This is nothing new. Already 15 years ago, researchers believed that vitamin E could reduce the risks associated with the pill. It was also known that the pill drains the body of antioxidants, which can be directly linked to an increased risk of blood clot formation. When one lacks vitamin E, the fats in the blood become oxidized, thereby stimulating the platelets to stick together causing the formation of blood clots. Logically, it was suggested that vitamin E should be combined with use of the pill.

The pill uses up the body’s vitamin E and Q10 reserves. This has been proven again, this time in a study where 15 users of the pill in their forties were compared with women in the same age group who did not take the pill. The differences found were statistically valid, and although this was a small study there were no doubts regarding the results. These results were known before the study was completed; the problem was that nobody had been paying any attention to them.

Unsolved problems
Why does the pill strain the bloods vitamin E and Q10 contents? The pill raises the body’s oestrogen levels. This is why the ovaries go into hibernation so that ovulation is inhibited. The body registers a hormone level high enough that the ovaries can take a break. Even normal (physiologic) levels of oestrogen stimulate the formation of free radicals and therefore cause an increased use of antioxidants. This has been shown in an American study of the cells which compose the inner walls of the blood vessels (endothelium cells). They also showed that free radicals resulting from the presence of oestrogen caused the cells to grow, causing the blood vessels to thicken. It is believed that this increases the risk of blood clots. It also indicates that antioxidants could prevent such side effects.

For practical purposes, women with an increased risk for side effects are advised not to take the pill. This includes women over the age of 35, women with high blood pressure, and so on. All women with an increased risk of blood clots should refrain from using the pill. This causes some amount of contemplation. Who knows if they are in the high risk group? Is their risk so low that a five fold increase in risk is acceptable?

Aside from these problems it is important to know that if you use the pill, your defence against the formation of free radicals is weakened. Even though this is well known, no one has, until recently, thought to reduce this risk with the use of antioxidants.

An important question follows: What is the long term prognosis for women who took the pill for many years when they were young? During the many years they took the pill, they had reduced levels of vitamin E and Q10 in their blood. In the short term, this increased the oxidation of the blood’s fats which increased the risk of blood clots. But does it cause problems in the long term like smoking and high blood pressure? As yet, we can only guess.

By: Vitality Council

References:
1. Palan PR Magneson AT, Castillo M, Dunne J, Mikhail MS. Effects of menstrual cycle and oral contraceptive use on serum levels of lipid soluble antioxidants. Am J Obstet Gynecol. 2006 May;194(5):e35-8. Epub 2006 Apr 21
2. Felty Q. Estrogen-induced DNA synthesis in vascular endothelial cells is mediated by ROS signaling. BMC Cardiovasc Disord 2006 Apr 11;6:16
3. Ciavatti M, Renaud S. Oxidative status and oral contraceptive. Its relevance to platelet abnormalities and cardiovascular risk. Free Radic Biol Med. 1991;10(5):325-38
4. Saha A, Roy K, De K, Sengupta C. Effects of oral contraceptive norethindron on blood lipid and lipid peroxidation parameters. Acta Pol Pharm. 2000 Nov-Dec;57(6):441-7.
5. Tanis BC, Rosendaal FR. Venous and arterial thrombosis during oral contraceptive use: Risks and risk factors. Semin Vasc Med. 2003 Feb;3(1):69-84
6. Crook D, Godsland I. Safety evaluation of modern oral contraceptives. Effect on lipoprotein and carbohydrate metabolism. Contraception. 1998 Mar;57(3):189-201

Smokers should get more vitamin C and E

Claus Hancke

April 1, 2006

Far too many people get too little vitamin E. The problem is especially large in smokers and can partially be solved by a supplement of vitamin C.

What do you do if you get too little vitamin E? Here is a suggestion: take more vitamin C.

Smokers have this problem more than any other group. They use vitamin E much faster than non-smokers. This is because tobacco smoke oxidizes and destroys the vitamin, which causes it to fail in the fight to protect the unsaturated fats of the body’s cells. Smokers therefore have a greater need for vitamin E than non-smokers. Because they have a greater need, it is easier for them to receive too little.

This is where vitamin C comes in. Vitamin C is easier to get a hold of than vitamin E. Because vitamin C is an antioxidant it can protect the vitamin E from oxidization by the free radicals of the tobacco smoke. This has long been believed, but, until recently, remained unproven in people. There has lately been a small scientific breakthrough in this field.

The study was done as a cooperative effort between a number of American universities and one Canadian university. 11 smokers and 13 non-smokers were given supplements of 50 mg vitamin E containing deuterium. By measuring the amount of deuterium in the blood the researchers were able to determine how fast the vitamin E disappeared from the smoker’s blood (plasma) and compare that to the changes in vitamin E levels in the non-smokers.

It disappeared, as expected, fastest in the smokers. In the course of 25 hours half of the marked vitamin E had disappeared. In the non-smokers this took 42 hours. But, when the smokers were given 500 mg vitamin C morning and evening, it took 34 hours for half of the marked vitamin E to disappear. The vitamin C protected the vitamin E reserves in the smokers, but did not bring them to the level of those in the non-smokers.

Far too few get enough
One can therefore see a normalising of vitamin E in smokers with the help of vitamin C. This is of course only true if the smokers receive enough vitamin E in the first place, which can be said of far too few.

To conclude the summary of this research is should be mentioned that only 8% of men and 2.4% of women receive the recommended 12 mg vitamin E (alpha-tocopherol) per day. This is highly likely no better in the U.K. The first and most important recommendation made is that smokers received the recommended amounts (for smokers) of both vitamins C and E (125 mg vit. C and 15 mg vit. E). The second recommendation is that more research be undertaken regarding whether other antioxidants can protect against the degradation of vitamin E. This is important.

But is it true that one needs 12 mg vitamin E per day? Yes it is! An earlier study has shown that the bodily tissue of healthy, young people uses about 5 mg vitamin E (alpha-tocopherol) per day.

Because one on average only absorbs about one third of ones food intake in the intestine, should one take a little bit more than the aforementioned 12 mg. But if one eats an especially light diet more should be taken. If breakfast is only cornflakes and low fat milk, taking a vitamin E supplement won’t do much good. Only a tenth of it will be absorbed.

Even young, healthy smokers should receive more vitamin E than others. Older people have an even greater need and it is apparent that most people don’t get enough.

By: Vitality Council

References
1. Bruno R S et al. Human vitamin E requirements assessed with the use of apples fortified with deuterium-labeled α-tocopheryl acetate. Am J Clin Nutr 2006;83:299-304
2. Bruno R S et al. α-Tocopherol acetate disappearance is faster i9n cigarette smokers and is inversely related to their ascorbic acid status- Am J Clin Nutr 2005;81:95.103.
3. Bruno R S et al. Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radical Biology & Medicine 2006;40:689-97

Vitamin E May Be Diabetic’s Saviour

Claus Hancke

December 20, 2005

About one out of every two diabetics has a five times larger than average risk of dying from heart disease. This risk can be cut in half by vitamin E. This is a well justified theory which is now being tested in a large Israeli study.

It is well known that the heart’s of diabetics become easily atherosclerotic, often causing them to die due to blood clots in the heart. Therefore, health officials work hard to combat atherosclerosis in diabetics. For example, diabetics are encouraged to take cholesterol reducing medicine, even when their cholesterol levels are very low. Diabetics’ blood pressure should also be low.

If one believes the Israeli researcher, Andrew Levy, the lives of even more diabetics can be saved by taking 400 units of vitamin E daily. Levy’s theory is now being tested in Israel in a large randomised study with 5,000 middle aged diabetics. Half of them will receive vitamin E for the next four years while the other half will not. If it goes as is hoped, the result will have enormous significance for public health.

It is optimistic to implement such an expensive study with vitamin E. As every (Danish, ed.) TV watcher knows, vitamin E doesn’t work against anything. Why would Levy and his co-workers from the Israeli Technion Technical Institute, where many Nobel prise winners can be found, go against the flow?

The explanation involves an antioxidant which few non-experts know of. It is called haptoglobin and is a protein which is created in the body. Haptoglobin binds the blood’s colouring agent, the iron rich haemoglobin, if it becomes detached from the red blood cells. In this way it prevents iron poisoning and therefore against overloading of free radicals in a long list of conditions where red blood cells die.

Disregarded effects of vitamin E
Levy and his co-workers have shown time and time again that haptoglobin works as an antioxidant. There is more to the story; haptoglobin is found in two forms, which are not equally effective antioxidants. Type 1 haptoglobin works much better than type 2. If one has type 2 haptoglobin (like 40% of the Israeli diabetics) the risk of death due to heart disease is five times higher than normal! In other words, a very large part of diabetics’ high death rate due to heart disease is because one out of every two of them has an insufficiency defence against oxidation because of ineffective haptoglobin.

The logical consequence of this enormous difference is, according to Levy, that the poorly protected diabetics with type 2 haptoglobin should take supplementary antioxidants. This is where the vitamin E study comes in. Vitamin E should be able to help. On the other hand, if it does help, why have other studies with vitamin E not previously shown this effect?

Levy believes that this is presumably because they have not been analysed with this effect in mind. He studied serum from a large sample of the ca. 10,000 participants in the Canadian HOPE study, where atherosclerotic participants received 400 units of vitamin E daily. The people behind the HOPE study found no effect of the vitamin E. But what about the 1,000 diabetics in the study? About a year ago, Levy proved that vitamin E reduced the risk of heart disease by 50% in the diabetic participants who had type 2 haptoglobin.
This surprising result was hidden in the HOPE study and was apparently unknown. This is quite educational. If the most threatened diabetics’ very high risk of heart disease can be halved with a cheap, harmless, vitamin E pill, the signification is very large.

Until 2010 we only have these results. There are no other results to turn to. It is not even possible to find out which kind of haptoglobin you have. If you wish to prevent heart disease, you have to do it in the dark. It is however risk free.

By: Vitality Council

References:
1. Andrew P. Levy et al. The Effect of Vitamin E Supplementation on Cardiovascular Risk in Diabetic Individuals With Different Haptoglobin Phenotypes. Diabetes Care 27:2767, 2004.
2. Levy AP et al. Strong Heart Study. Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Cardiol. 2002 Dec 4;40(11):1984-90.
3. Suleiman M, et al. Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction. Diabetes. 2005 Sep;54(9):2802-6.
4. A survey of the study can be found at Clinical Trials.gov: www.clinicaltrials.gov/ct/gui/show/NCT00220831.

care.diabetesjournals.org
www.cardiosource.com/jacc/index.asp
www.clinicaltrials.gov/ct/gui/show/NCT00220831
www.iom.dk

Vitamin E Lowers Cholesterol Levels in Diabetics

Claus Hancke

December 13, 2005

There are at least eight different kinds of Vitamin E, but typically we only get one of those in vitamin pills. One of the other kinds prevents arteriosclerosis, while a third kind has been shown to effectively lower the blood cholesterol levels of diabetics.

When you buy vitamin E in pill form, you almost always get alpha-tocopherol. Alpha-tocopherol (natural and sometimes, unfortunately, synthetic) has also been used exclusively in almost all of the studies on vitamin E’s effectiveness against cardiovascular disease.

There are other tocopherols than alpha-tocopherol. They all share the same basic chemical structure but differ in their side chains. Tocopherol can come in alpha, beta, gamma, or delta forms depending on the position of its side chains. Apha-tocopherol, the type used in vitamin pills, has the greatest effect as a vitamin.

Tocotrienols, another vitamin E form, are less well known. They differ from the other forms by having three double binds in their side chain. They are found in palm oil as well as grains such as oats, barley, rice, and corn. Tocotrienols can also be found in alpha, beta, gamma, and delta forms.

These tocotrienols are coming into the spotlight. For many years, on the basis of animal studies and small studies using humans, there has been the suspicion that they are effective against atherosclerosis. For example, ten year ago an American randomised study with 50 test subjects showed that tocotrienols from palm oil definitely counteracted atherosclerosis of the carotid arteries. Unfortunately no follow up study has been preformed.

Recently an Indian randomised study has surfaced. It shows that tocotrienols from rice sources sink the cholesterol concentration in the blood of type 2 diabetics (old age diabetes). In this study 19 diabetics received placebos for a period of 60 days. Before or after this 60 period they received, for a similar period, capsules containing rice with high concentrations of tocotrienols (each participant received 3 mg tocotrienol per kilo bodyweight per day). The study was designed so that no one knew which participants received which pill at what time until the study was completed.

Unsolved problems
The results showed that the tocotrienols reduced the total cholesterol levels of the participant’s blood by no less than 30%. Even more encouraging, the “bad” cholesterol, (LDL cholesterol) which can become oxidised and cause atherosclerosis, fell by an astonishing 42%. This effect is just as pronounced as seen with traditional cholesterol lowering medication, the so called statins.

It seems that anyone who can get a hold of tocotrienols is free from seeking traditional cholesterol lowering treatment. But before this is certain and becomes common practice, a few things should be further looked analysed.

First and foremost, can the results of the aforementioned study be reproduced? As stated earlier tocotrienols were effective against atherosclerosis in the carotid arteries, but in the study which showed this effect, the participants’ total cholesterol was unchanged! Tocotrienol does not always lower cholesterol. But does it always counteract atherosclerosis? At best the answer is maybe, we don’t know. After looking at the results of the two studies we can hypothesise that the differences in their results could be the result of the different tocotrienol blends used. The first study used a palm oil extract while the second used a rice source. The differences between alpha, beta, gamma, and delta tocotrienol is sufficient, their effects should differ.

Other things which we understand even less could also play a role. The likely cholesterol lowering effect of the rice tocotrienol should also be tested for possible side effects and the results of this should be compared with the side effects of traditional cholesterol medicine. A big job awaits researchers.

Meanwhile, the studies have shown with certainty that (apart from that oatmeal and brown rice are healthy) we are not finished with vitamin E or, more to the point, the E vitamins. There are many of them, and they have different effects. Their potential is very promising.

By: Vitality Council

References:
1. Tomeo AC, Geller M, Watkins TR, Gapor A, Bierenbaum ML. Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids. 1995 Dec;30(12):1179-83.
2. Qureshi AA, Salser WA, Parmar R, Emeson EE. Novel tocotrienols of rice bran inhibit atherosclerotic lesions in C57BL/6 ApoE-deficient mice. J Nutr. 2001 Oct;131(10):2606-18.
3. Baliarsingh S, Beg ZH, Ahmad J. The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis. 2005 Oct;182(2):367-74. Epub 2005 Apr 20.

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www.athero.org
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False Propaganda Against Vitamins

Niels Hertz

November 30, 2005

A frightening warning in an article in the Danish newspaper, Ekstra Bladet, claims that people will get sick from taking Vitamin B and injure their hearts by consuming Vitamin E. These claims are twisted and false.

Condescending evaluations of vitamin supplements are quite common. They rarely come from experts, but often from people who know something about something else and therefore think they know something about everything.

As a rule, it is stated that the vitamins only provide expensive urine and do not help against anything at all. Sometimes this message is spread rather too thickly.
The vitamins are poisonous! As the other day in a large published article in the newspaper Ekstra Bladet: You get sick from nutritional supplements, the headline stated. Further down, it became clear that you would not only get sick. You would die!

Whenever these kinds of statements appear, people get scared. They cannot imagine that anyone will write anything in Ekstra Bladet if it is not true. But unfortunately there are writers who don’t bother with that. This is evident from the mentioned article, which is mainly based on two gross, false claims. Here we comment on them in reverse order.

“The last new thing was the B vitamin folic acid, which should also be able to protect against heart disease. Recently, a large Norwegian study showed that folic acid did not make users less prone to heart disease. On the contrary, they got sick from the pills”.

Is that right? No. It is wrong. In the Norwegian randomised trial (it was called NORVIT), approx. 900 people who had had blood clots in the heart were supplemented with 0.8 mg of folic acid per day for 3-4 years. The table shows the relative mortality and incidence of heart clots in those who received folic acid and those who received inactive pills (placebo.)

……………………..………..……Folic acid……Placebo
Blood clot in the heart…….57,9…………….59,2
Total mortality………………….28,7…………….31,7

As seen, the overall mortality was 9% lower if folic acid was given instead of placebo. The risk of blood clots was also reduced. How does that agree with the fact that people “got sick (meaning heart disease) from the pills”? The answer is that it is not true. Admittedly, none of the differences were statistically significant. It was a trend. But that is not the same as the study showing the opposite of the trend.

And now to the first claim. It is about vitamin E. It was claimed that vitamin E should protect against heart disease, it says, but “when the major scientific studies came, it turned out that it… gave… heart failure, bleeding and an increased risk of dropping dead”.

Heart failure. That claim must come from the HOPE-TOO study, the only one of the many studies with a total of well over 100,000 participants in which heart failure has been found to be caused by vitamin E treatment.

4,000 people with severe atherosclerosis participated in HOPE-TOO. Those who received vitamin E (400 IU/day) had slightly more often weakened heart. The difference was statistically uncertain, i.e. that it could be accidental. The absence of heart failure in all the other studies suggests the same.

On the other hand, a slightly reduced risk of lung cancer was found in HOPE-TOO, and it was reliable. But since this has not been found in other studies either, it is unreasonable to mention it. It could be random anyway.

Another peculiarity of HOPE-TOO was that even though the participants were given 25 times the recommended amount of vitamin E, it could not be seen in the blood tests. On average, the participants had very little vitamin E in their blood, despite the large supplements. The concentration in the blood (17.6 mmol/l) was even at the lower end of the normal range (12-42 mol/l). Either the participants have not taken the vitamins, or they have e.g. taken them on an empty stomach so that they were not absorbed from the intestine. So where does the vitamin E study end up?

In other words: Here a single, guaranteed misleading, result from one small experiment is misused – as “fact”. It is cheating and distortion. And for the record: That you should start bleeding, let alone die from vitamin E in the mentioned doses, is out of thin air. In contrast, the vitamin prevents, in animal experiments, gastric bleeding caused by aspirin.

Professor Maret Traber, Oregon State University, is considered one of the world’s leading vitamin E researchers. She recommends vitamin E for a number of chronic health problems, including heart disease. Louis Ignarro, who received the Nobel Prize in 1998 for his research on blood vessels, unequivocally recommends vitamin E and C for the prevention of atherosclerosis. It works, he says.

Of course, what even such big celebrities think is no argument in itself. It is the substance that counts. Yet. If you are free to choose your advisers, you are likely to prefer the most knowledgeable – and the most reliable.

By: Niels Hertz  MD

References:
1. A. Astrup. Du bliver syg af kosttilskud. Sund og Slank. Ekstra Bladet. 26.11.05.
2. The HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer. JAMA 2005;293:1338-47.
3. Bonaa KH. NORVIT: Randomized trial of homocysteine-lowering with B-vitamins for secondary prevention of cardiovascular disease after acute myocardial infarction. Program and Abstracts from the European Society of Cardiology Congress 2005; September 3-7, 2005; Stockholm, Sweden. Hot Line II. Iflg. Linda Brooks. NORVIT: The norwegian vitamin trial. Medscape Sept. 2005. (Not published in printed media.)

Antioxidants Halve The Damage Of Brain Hemorrhage

Claus Hancke

October 6, 2005

Countless animal studies have shown that the brain injury following a brain hemorrhage can be reduced dramatically with antioxidants. Several clinical human studies are now being conducted.
Next to heart disease and cancer, brain hemorrhage is the most common cause of death in Western countries. Among those who survive, many will face severe difficulties in the years ahead with chronic brain injuries and paralysis. But more and more people will experience a brain hemorrhage because of an increasing number of old people.

Can this gloomy perspective be mitigated? Numerous trials have shown that antioxidants can both prevent brain hemorrhage and reduce subsequent brain injury if the accident nevertheless occurs. This fascinating topic has just been elucidated in a robust overview of researchers from the pharmacological laboratory at the Rene Descartes University in Paris.

Contrary to popular belief, a brain hemorrhage is rarely a hemorrhage. It is far more often a blood clot, which either forms on the inside of one of the brain’s large arteries – in the same way as a blood clot in the heart – or is supplied with the blood. Regardless of the language confusion, the result is the same: parts of the brain on the blocked side get no oxygen and perish, while the victim becomes more or less paralyzed on the opposite side.

This is where the antioxidants come in. They fight free oxygen radicals, which are responsible for the majority of brain damage. The free radicals are formed during a lack of oxygen, but paradoxically, it is not an absolute advantage when the organism breaks down the blood clot itself – or when it is broken down medically, which can more or less be done up to three hours after the first symptoms. The renewed blood supply – this is called reperfusion – unfortunately leads to a massive production of free radicals – and thus further brain damage.
Regardless of whether the blood supply resumes or not, things can go wrong.

Why do these free radicals occur in tissues that do not receive blood or that have only temporarily been lacking blood? The article reviews the possibilities. Certain enzymes e.g, which normally inactivate free radicals, stop functioning. In addition, the weakening of the mitochondria – the energy factories of the cells i.a. – play a role. It is the mitochondria that process the oxygen, and when they weaken, the free (oxygen) radicals leak. It has been proven that the more free radicals are formed, the worse the brain damage.

It is therefore logical to believe that antioxidants can limit the damage. This is also true of a large number of experiments on animals. Here, damage has been reduced by more than 50% by pre-treating the animals with antioxidants such as NAC (n-acetyl-cysteine), resveratrol (the colorant in red wine), lipoic acid (a beneficial and harmless food supplement that is banned in Denmark) or melatonin ( also beneficial, harmless and forbidden for Danes).

With vitamin E, it has also been possible to halve the damage – or more. Of course, it worked best when the treatment was started quickly. Quick help is double help.

There are now several clinical trials on humans, but the difficulty is that you cannot predict when or if a person will have a brain haemorrhage. In the trials, the treatment is only started when the brain haemorrhage has occurred. There are no reliable results yet, and the antioxidants that are tested are unfortunately synthetic substances, which can be patented (and later sold as expensive drugs): Tirilazad, Ebselen, Edavaron and NXY-059. Edavaron is recognized as a treatment in Japan.

What can ordinary people do? The review concludes that antioxidants are “certainly some of the most promising agents against cerebral hemorrhage” and that they are of “great interest” in combination with the medical breakdown of blood clots used today.
You have to choose yourself. But it is worth noting that a solid intake of antioxidants seems to be able to prevent – perhaps tragic – consequences of a brain haemorrhage.

By: Vitality Council

Reference:
Isabelle Margaill et al. Antioxidant strategies in the treatment of stroke. Free Radical Biology and Medicine 2005;39:429-43.

Perhaps Prostate Cancer may be a Rarity in the Future

Claus Hancke

April 1, 2005

Every forth man lives with a highly increased risk of getting cancer of the prostate, the next most frequent cause to cancer deaths in men. It does not have to be like that. Exactly these exposed men could easily decrease their risk to a tenth.

Researchers from Harvard University in Boston have published a landmark study. It strongly suggests that most cases of cancer in the prostate are due to lack of balance in the body’s defense against free oxygen radicals. And most importantly: This balance can be restored with antioxidants – especially with selenium, but also vitamin E and the red dye of the tomatoes, lycopene. Prostate cancer can thus become a rare disease.

The imbalance occurs especially in men who get too little selenium and who, for hereditary reasons, have a particularly effective antioxidant enzyme (manganese-containing SOD) in their mitochondria. The mitochondria are the cells’ internal energy factories, which are worn down by free oxygen radicals with age. This wear and tear, parenthetically noted, is believed to be a very significant cause of aging and age-related diseases.

One would therefore think that it was an advantage to have a particularly effective antioxidant enzyme in one’s mitochondria. But very often it is not. The SOD enzyme transforms free oxygen radicals into the less risky hydrogen peroxide, but this creates a new problem: the hydrogen peroxide must also be removed, since it also causes harmful oxygenation. The removal requires an enzyme (glutathione peroxidase), the quantity of which depends on the supply of selenium.

The more free oxygen radicals (e.g. from smoking) that need to be neutralized and the more efficient the SOD enzyme is, the more harmful hydrogen peroxide accumulates and the greater the need for selenium.

Balance in things
The Harvard study is part of a study of approx. 15,000 American doctors who have been followed since 1982. Around 1990, 275 of them had developed serious prostate cancer, and it was those who were primarily found interesting.

By: Vitality Council

References:
1. Haojie Li et al. : Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer. Cancer Res. 2005;65:2498-2504.
2. Woodson et al. Manganese superoxide dismutase (MnSOD) polymorphism, α-tocopherol supplementation and prostate cancer risk in the α-Tocopherol, β-Carotene Cancer Prevention Study. Cancer Causes Control 2003;14:513-8
3. Niels Hertz. Selen – et livsvigtigt spormineral. Forlaget Ny Videnskab 2002.

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