Tag: antioxidants

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.

Much ado about nothing

Claus Hancke

February 12, 2019

One could justifiably use the above-mentioned Shakespeare title about a newly published article (1) that supposedly shows that antioxidant supplements reduce the effectiveness of chemotherapy and radiation therapy in postmenopausal women.

Please note that this assertion is by no means proven; there is much research that points in both directions.

The above-mentioned journal article does not contribute to clarification of the issue, not least because of the weak design of the study.

The data in the study came from interviews of postmenopausal women in two regions in Germany. The researchers used data from the “Mamma Carcinoma Risk Factor Investigation,” a study that was first published more than 10 years ago to report on the risk factors associated with postmenopausal hormone therapy.

Despite the known weaknesses of the interview study, the Danish TV2 reported the results of the study as a great sensation and with a headline that announced:

“New research: Dietary supplements can spread breast cancer.
German researchers have learned that antioxidant supplements can worsen breast cancer in women. The Danish Cancer Society is concerned.
For many years, there have been discussions as to whether antioxidant supplements are good for human health or not. And now a German study makes it clear that they are definitely dangerous for women with breast cancer.”

No, no, and no again.

There is no evidence for the dramatic TV2 news statements.

The German study does not make anything clear.

And the journal article authors’ own conclusion is much more cautious than the TV2 news report.

The journal article authors write:

“Our data do not support an overall association of postdiagnosis supplement use with prognosis in postmenopausal breast cancer survivors. Our results, together with other clinical and experimental evidence, suggest that during breast cancer treatment, antioxidants should potentiall be used with caution.”

In their journal article, the authors do not even advise against the use of antioxidants during chemotherapy and radiation therapy. They just urge caution.

Normally, German research results are shrugged off in Denmark, and interview-format studies get the same treatment. But, this time, the German interview study could be used to advance specific points of view, and so it was.

There are many things in this German study that grab the attention of the alert reader, and a close reading of the study reveals that the authors are biased, not least in their selection of earlier research on the topic.

An interview study, with no blinding of at all, is certainly not the most valid form of research and cannot be compared with prospective randomized controlled trials (RCT’s).

In the German study, the researchers asked some 2000 breast cancer patients whether they took antioxidant supplements before and/or after the time of their diagnosis with breast cancer and/or during their chemotherapy and radiation therapy.

The women in the study were to answer yes if they had just taken one or another supplement three days a week for a year at a given point in time. A “current user” was any woman who used supplement postdiagnosis within the 6 months before the first follow-up interview.

The term “supplement” and the term “antioxidant” are used quite sloppily but with a noticeable consistency. Whenever the researchers discuss the study, the usage, or the statistics, they use the term “supplements.” Whenever they discuss the chemotherapy or the radiation therapy, however, they use the term “antioxidants” without specifying what the term “antioxidants” covers.

In other words, the researchers have had to extend the definition of antioxidants with other supplements in order to achieve sufficient statistical power and thereby just barely sneak over the line into statistical significance.

About this, the authors write in their article:

“The main exposures of interest included postdiagnosis use (no postdiagnosis use, postdiagnosis use, current use) of any type of supplement; specific supplements, such as magnesium and calcium; and supplement group, such as antioxidants, in which there was adequate statistical power to conduct analyses. Only a few women reported postdiagnosis use of multivitamins, vitamins A, C, E, zinc, and selenium, and therefore they were collectively evaluated together as antioxidants in all of our analyses.”

Above and beyond the fact that the researchers have jumbled everything together in a big group that they call “antioxidants,” there is also a total lack of information about daily dosages, single dosages, and preparation types.

This study has a weak design and has unclear results. Therefore, the authors are careful to settle for a cautious conclusion, which speaks for itself.

The misinformation occurs when the Danish media then trumpet the study conclusion as the definitive truth.

Any serious researcher would avoid making such bombastic statements.

Litt:

  1. Jung AY et al. Antioxidant supplementation and breast cancer prognosis in postmenopausal women undergoing chemotherapy and radiation therapy. Am J Clin Nutr 2019;109:69–78.
  2. Flesch-Janys D, Slanger T, Mutschelknauss E, Kropp S, Obi N, Vettorazzi E, Braendle W, Bastert G, Hentschel S, Berger J. Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy. Int J Cancer 2008;123(4):933–41.

Contradictions about vitamins

Claus Hancke

 April 26, 2012

One may wonder about the Danish newspapers’ poor interest in the latest vitamin report. First of all, the report predicts dead to those who take vitamin pills, secondly, the turn-over for vitamins is one and a half billion kroner a year. The subject must interest many.

Here the report itself will not be discussed. It is already commented. On the other hand, attention must be paid to a very serious issue concerning the marketing of the report: The contradictory statements that a prominent researcher has used the report to make.

The statements are from chief physician Christian Gluud from Rigshospitalet. He has previously said peculiar things. It’s hard to forget how he on television declared antioxidants (like vitamin E and vitamin C) to be carcinogenic, even when they occur in fruit and vegetables. However, in fruit and vegetables there was, he believed, “a lot of other substances that might either correct the potential damage caused by the antioxidants or that could completely neutralize them.”

You might consider this amusing statement the next time you eat broccoli. It is thus an antidote to vitamins, you are eating!

Currently, Gluud said on TV that his latest study, which combined the results of different trials, is based on trials with commonly recommended vitamin doses. And yet, in almost all trials, there were used from five to twenty times the recommended dose or more.

Gluud has further said (the news program Deadline 2.4.2012) that his group has revealed that, for example, the antioxidants Vitamin C and selenium are directly life threatening, as they increase mortality by 4%. And yet, his report frees both of the two antioxidants for this accusation.

In the TV2 news (22.3.2012) Gluud said that “it’s quite common vitamin pills in very common doses that give the increased mortality.” But in an interview with Medwatch.dk he said the opposite: He could not comment on that subject – that multivitamins increase mortality – because no one had studied it!

If you ask chief physician Gluud, you may obviously get the answer that his current state of mind indicates. One moment, common vitamin pills are dangerous poisons, the next, it is not known, and at one time, selenium and vitamin C are poisonous, but at another time and towards another audience – those who read the report – they are harmless.

The contradictions do not prevent Gluud from hoping that the report will have “a practical and industry related consequence,” as he says. What that means is easy to understand. Gluud is/has been chairman of a lobby group that has sought to influence the European Commission to prevent the free sale of vitamins. They must be made into drugs, which in practice will push small vitamin companies out of the lucrative market, which alone in Europe is more than $ 20 billion a year.

When a researcher is politicizing, he invariably throws a dubious light over his research, justly or not. Worse, however, is when the researcher is facing the public, on a topic of great importance, against better knowledge.

In doing so makes him disqualified.

By. Niels Hertz, M.D

Vitamin C inhibits cancer. But How?

Claus Hancke

September 18, 2007

New research sparks new theories about how vitamin C inhibits cancerous growth.

A great deal of research indicates that vitamin C has a considerable inhibitory effect on the growth of cancer cells.

The biochemical effect of high-dose treatment with vitamin C is reasonably understood; vitamin C acts as a pro-oxidant on cancer cells at such doses. This causes increased free radical strain on the cancer cells and thereby acts as a poison to the cancer.

In moderate doses, the kind of doses which we can get through our diets, vitamin C is an antioxidant. But even at these doses, vitamin C has shown an inhibitory effect on the growth of cancer cells.

It was therefore believed that vitamin C blocks the free radicals which cause the cancer forming mutations in the cells, and that the reason for its protective effects is that it protects the cells’ DNA.

This is presumably not the whole truth.

Many years ago a famous professor by the name of Warburg was among the first to maintain that cancer cells grow in oxygen poor tissue. Today this is common knowledge, but there lacks knowledge on how this occurs. Ten years ago Gregg Semenza of John Hopkins University found that cancer cells are dependent on a protein called HIF-1 (hypoxia induced factor), which helps the cells by compensating for lacking oxygen in the surrounding tissue and thus allows cancer cells to convert sugar to energy without oxygen. HIF-1 also catalyses the creation of new blood vessels so that hungry cancer cells can get fresh supplies of nutrients and oxygen. If a cancer grows aggressively, it quickly uses up its oxygen supply and becomes entirely dependent on HIF-1. The HIF-1 protein is dependent on the presence of free radicals, which are also necessary for many other processes in the body. A powerful antioxidant like vitamin C eliminates the surplus of free radicals, which causes HIF-1 to become ineffective and thus inhibits cancer growth.

This new theory is based on a study done by a research group at the centre of oncology at John Hopkins University in conjunction with Dean Felsher of Stanford.

They set out to study antioxidants’ roles in cancer growth and found, to their great surprise, that antioxidants destabilise the protein on which cancer cells are dependent. As professor Chi Dang from John Hopkins University wisely stated, “By uncovering the mechanism behind anti-oxidants, we are now better suited to maximize their therapeutic use.”

By: Claus Hancke, MD

Reference

HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo. Cancer Cell, Volume 12, Issue 3, 11 September 2007, Pages 230-238Ping Gao, Huafeng Zhang, Ramani Dinavahi, Feng Li, Yan Xiang, Venu Raman, Zaver M. Bhujwalla, Dean W. Felsher, Linzhao Cheng, Jonathan Pevsner et al.

www.cancercell.org

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

Antioxidants against macular degeneration and blindness

Claus Hancke

March 9, 2006

Antioxidants can delay the most common cause of blindness in Denmark. It looks like they also can prevent it. Other supplements can possibly directly improve the sight – if they are taken early enough.

The most common cause of blindness in the U.K. is macular degeneration, also known as AMD. AMD is the age related degeneration of the area of the eye (retina) where light is collected, like rays hitting a magnifying glass, causing sharp sight. This degeneration thereby causes blurred sight. Thousands of people in the U.K. are affected by AMD each year. Many more suffer from other forms of poor sight.

The more mild forms of AMD are quite common. With these forms, sight is reduces to such a small degree that the loss is normally not noticed. Optometrists can ascertain such mild forms of AMD with the finding of small yellow spots on the retina under an eye exam. These defects are composed of accumulated waste products. Almost everyone over the age of 50 has at least one such defect. Small defects are unimportant, even when there are many. But, if they are larger there is a risk of serious AMD. About 30% of those with larger defects will have advanced AMD within five years.

Therefore it created a sensation when, in 2001, an American study showed that this five year risk could be reduced to 20%, meaning by a third, with the supplement of zinc and antioxidants. The doses given in the study were: 500 mg vitamin C, 400 units vitamin E, 15 micrograms beta-carotene as wall as no less than 80 mg zinc per day. Treatment with antioxidants alone appeared to be just as effective, but could not be proven statistically.

But how does one know if one has the early stages of AMD? Because the loss of sight in such cases is minimal, one might not go to an eye doctor. Therefore it is recommended that everyone over the age of 55 undergo an eye exam so they can consider whether or not they should take supplements. Because beta-carotene has been reported to cause lung cancer in smokers, this advice is only relevant to non-smokers.

Antioxidants can also inhibit the development of AMD, but this use is not often considered. The question however remains whether antioxidants can prevent AMD from occurring in the first place. A new Dutch study implies that they can.

Sharper sight
In this study 6,000 residents of Rotterdam were followed starting from the years 1990-93. In 2004 560 of them had AMD, but it was not entirely random who developed AMD. Both a high intake of zinc and vitamin E lowered the risk, but only a little. If one received high doses of both vitamins C and E, beta-carotene and zinc, the risk of developing AMD was reduced an impressive 35%.

An Italian randomised study published last year showed even more intriguing results. In this study 106 patients with an early form of AMD were treated over the course of a few years with a combination of fish oil (n-3 fatty acids), the antioxidant Q10, as well as the dietary supplement, carnitine. The goal was to improve the fatty acid metabolism of the retina. Carnitine advanced the metabolizing of fat such that the depositing of waste products was counteracted. This is important in the retina seeing that the concentration of n-3 fatty acids is even richer than in brain tissue. 30% of the matter in the retina is composed of n-3 fatty acids as opposed to 20 % in the brain.

The result, with regards to light sensitivity in centre of the eye, visual acuity (measured with a normal eye chart), and perceptual changes in the retina, was not only the progress of the disease was stopped, but that there was also a direct improvement! The area of the eye where defects could be seen was not just unchanged, but had shrunken! All of this was statistically sound.

With advanced AMD one is both blind and can see. One cannot read, watch TV, or recognize faces. But peripheral vision is retained. One can see out of the corner of the eye, so it is still possible to orientate oneself in space and walk, with care. This functional blindness can, in many cases, be improved by antioxidants and, according to the above mentioned research; the condition can even be improved by simple dietary supplements, if they are taken in time.

By: Vitality Council

References:
1. Age-Related Eye Disease Study Research Group.Arch Ophthalmol. 2001 Oct;119(10):1417-36. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.
2. Feher J et al. Ophthalmologica. 2005 May-Jun;219(3):154-66.Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10.
3. van Leeuwen R et al. JAMA. 2005 Dec 28;294(24):3101-7. Dietary intake of antioxidants and risk of age-related macular degeneration.

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By all Means: Enjoy a great Sauce!

Claus Hancke

February 11, 2006

One of the know-it-all expert councils has turned out to be wrong – again! A diet without fat does not benefit health.

When it comes to nutrition, the word from on high should be reconsidered. There are many who preach old advice with enthusiasm, sometimes without spouting a glimmer of truth. Nutrition is a question of religion. But it has been ten years since margarine was pushed off its pedestal, two years since sugar fell, and now the end is near for light products.

For years we have been brainwashed to believe that we must eat lean foods in order to be healthy and thin. Even though it seems obvious, this dogma has received some criticism in recent years; including from the results of multitudes of studies where fatty foods replaced easily absorbable carbohydrates. Despite these results, supporters of the old dogma recently had wind in their sails when a well known American nutrition expert misinterpreted a study and claimed that there was proof that when one eats pasta, potatoes and bread, one becomes thin.

Nobody noticed that the study had proven the opposite. Even when one eats lean foods for seven years, there is only a 400 g weight loss. Pasta and bread were not what it took to achieve this miniscule weight loss. In the study more fruit and vegetables made the food light, whereas intake of pasta and corn products was reduced by 20%.

We are used to being led astray, but now we can set the fact that in practice one does not become thinner by avoiding fat in stone. But that isn’t all; three other parts of the same study (Women’s Health Initiative) have now shown that one does not become healthier by avoiding fat.

In any event, a healthy woman between the ages 50 and 79 years cannot count on avoiding breast cancer, colon cancer, stroke, or coronary disease by reducing fat intake by 25% for eight years. Nor does it play a role for her to simultaneously increase fruit and vegetable intake from four to five portions daily.

A large and very thorough interventions study has shown this. It has been called the “Rolls Royce” of studies and it has been so expensive (three billion dollars) that it probably will never be repeated. The conclusions that we must make must therefore be taken from this study.

48,836 American women have participated. Of these 40% were placed on a diet while the rest were used as controls. Typically the women were slightly overweight but, even though they set their fat intake down from 38% to 29% of their caloric intake, they lost very little weight (waist measurement was reduced by an average of 0.8 cm). Blood pressure and cholesterol fell just as little, and the risks of falling ill with the aforementioned diseases did not change.

What was not studied
“The results for all three studies is a complete nothing,” declared leading researcher Michael Thun of the American Caner Society.

“The results must be taken seriously. Diet does not protect at all,” stated statistician David Freedman of Berkeley University. He added: “We in the scientific community often give conclusive advice based on weak groundwork. There we must do experiments.”

But does all this mean that what we eat is not important. Not even close – of course not! One must consider everything that the study did not take into account.

In the first place, there was no focus placed on the use of fish. The Italian intervention study, GISSI, which included 12,000 participants, showed a few years ago that just three grams fish oil daily reduced cardiac death in a high risk group by 30%. It is not the amount, but the kind of fat that is important.

Neither was there focus put on antioxidants. But according to a large American randomised study from 1996, supplements of the antioxidant selenium (200 microgram per day) reduce the risk of many forms of cancer by up to 50%.

That antioxidants are interesting was also seen in the seven year French SUVIMAX study form 2004. Here a fall in mortality was seen in men who received a number of antioxidants (selenium, zinc, vitamins C and E, zinc, and beta carotene) in moderate doses.

Nor was there focus on vitamin D, which is believed to have a future in the prevention of prostate cancer, enlarged prostate, breast cancer, arthritis, among others. Folic acid, which is believed to prevent breast cancer, osteoporosis, and more, was also lacking from the study.

The list could easily be longer. The important find of the study is that the dietary advice that experts have given out for years, without any doubts at all, has been disproved! It has only benefited the lucrative industry of light products.

This should be a wake up call in all camps. When is one an expert?

A study involving an increased fat intake has actually not been made. Therefore results of eating in this way are as yet unknown. Maybe we should just concentrate on eating fat of a higher quality that we are used to. Let us enjoy good butter and healthy olive oil.

By: Vitality Council

References:
1. Prentice R et al. Low fat dietary pattern and risk of invasive breast cancer. JAMA 2006;295:629-42.
2. Buzdar A U. Dietary modification and risk of breast cancer. JAMA 2006;295:691-2.
3. Kolate G. Low-fat diet does not cut health risks, study finds. The New York Times 8.2.06.
4. Beresford S A A et al. Low-fat dietary pattern and risk of colorectal cancer. JAMA 2006;295:643-54.
5. Howard B V. Low-fat dietary pattern and risk of cardiovascular disease. JAMA 2006;295:655-66.
6. Appel L A. Dietary modification and CVD prevention. JAMA 2006;295:693-5
7. Howard B V. Low-fat dietary pattern and weight change over 7 years. JAMA 2006;295:39-49.

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.

Green Diet And Antioxidants Act Against Prostate Cancer

Claus Hancke

August 16, 2005

A radically changed lifestyle together with antioxidant supplementation seems to stop the growth of early prostate cancer, while the blood becomes eight times more capable of fighting cancer cells.

Some studies with humans and numerous animal trials and population surveys have indicated that antioxidants counteract cancer. Nevertheless, only a few researchers have examined whether they help against cancer in humans when the disease is a reality. An American trial now shows that this may be the case, at least by cancer in the prostate.

The trial, which has just been published, included 93 men with early-stage prostate cancer. They were selected because they had refused to accept usual cancer treatment.

44 of them were instructed to follow a fairly strict diet where only 10% of calories were allowed to come from fat. They had to have a pure plant diet and avoid dairy products, but in return received a protein supplement in the form of a soy drink. In addition, they had to exercise equivalent to half an hour of brisk walking a day and had to perform various yoga exercises and meditate for another hour. Of course they weren’t allowed to smoke!

You’d think most people would quickly give up such a strict lifestyle. But the vast majority persist, perhaps because they are doing well. The leader of the trial, Dean Ornish, has described that when he let a group of men with bad hearts follow this recipe, their atherosclerosis in the coronary arteries of the heart decreased – mind you, not just in the first year, but quietly in a continuing process that all in all lasted at least five years.

In the current trial, however, Ornish supplemented with nutritional supplements:

  • Vitamin E 400 units/day.
  • Vitamin C: 2 grams/day.
  • Selenium: 200 micrograms/day.
  • Fish oil: 3 grams/day.

Better after a year
All had the so-called PSA value measured, first at the start of the experiment, and again after one year. PSA (Prostate-Specific Antigen) is an approximate expression of the spread of the cancer. That was the main purpose of the trial to measure what happened to PSA.

What happened was that when a year had passed, the PSA value had fallen by an average of 4% in the 44 in active treatment, while that in the control group – which was closely followed by their own doctor – had increased by 6%.

That in itself was an exciting result. But in addition, six men from the placebo group became so ill that they had to withdraw from the trial and undergo traditional treatment. If the six men from the control group had not dropped out – because they became very ill – the difference would have been even greater.

No actively treated patients left the trial
As a supplement to the PSA measurements, one more experiment was performed. They took serum from all participants and examined how it affected the growth of prostate cancer cells in laboratory experiments. After a year, a huge difference had emerged: the treated men’s serum inhibited the growth of cancer cells eight times as much as the control group’s!

These results are statistically very confident. One must therefore expect that there is an effect, but what causes it? Was it the predominantly green diet, soy, exercise – or perhaps yoga and meditation? Or was it the antioxidants?

One can only guess. Dean Ornish believes that overall lifestyle changes made the difference. But the assumption that antioxidants help against cancer is of course supported. In any case, the experiment is highly thought-provoking.

By: Vitality Council

References:
Ornish D et al. Intensive lifestyle changes may affect the progression of prostate cancer. The Journal of Urology 2005;174:1065-70.
Ornish D et al. Intensive lifestyle changes for reversal of coronary heart disease. JAMA 1998;280:2001-7.

The Role of Antioxidants May Have To Be Reassessed

Claus Hancke

February 27, 2004

British scientists have discovered that it is enzymes and not antioxidants that are the active factor, when white blood cells attack bacteria.

Free radicals are aggressive molecules that are capable of destroying the structure of other molecules. For example, the body uses free radicals to cut large molecules into pieces and build complex protein structures. So far so good.

But an abundance of free radicals has been shown to be able to damage the body due to the deterioration (oxidation) of certain molecules, such as LDL cholesterol, which then becomes dangerous because it causes arteriosclerosis in its rancid (oxidized) form.

In order to slow down this harmful oxidation, we form the so-called antioxidants. These are also found in our diet and in several dietary supplements. For example, vitamins C and E are such antioxidants.

However, a British research team has investigated the reactions that occur in the white blood cells when these attack bacteria. And they found that free radicals did not play a role, but rather that it was enzymes that the white blood cells use to attack and destroy bacteria.

Until now, it has been believed that the white blood cells used free radicals, and therefore people have been reluctant to use excessive doses of antioxidants, because it was believed that this would neutralize the white blood cells’ free radicals, so that they could not fight bacteria.

The new theory may explain why even large doses of antioxidants have not shown an inhibitory effect on the antibacterial effect of the white blood cells.

A large number of questions now remain, including the scientifically documented inhibitory effect on the occurrence of cancer and cardiovascular diseases.

There is no doubt that there will be renewed debate about this every time we see new research in this very exciting area. – Also because opinions are divided. But one thing is theory, another is practice.

We must remember that the knowledge of medical science today is wrong. All the history of science has taught us that. In 100 years, our current theories will be replaced by new ones, and people will smile at the official knowledge of today.

We must therefore be careful, and above all let ourselves be guided by the large clinical studies. The theories must then try to explain these results.

By: Vitality Council

Reference:
Nature, vol 427;6977:853.

www.nature.com/index.html
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