More is not always better

November 13, 2020

Dose response is diverse

Our body and cells react differently to the chemical substances we come into contact with. Our body’s reaction (response) to different concentrations (doses) is called dose-response. Small variations in the structure of substances can be decisive for the body’s reaction to the substances. For several groups of substances, it is known that they can be problematic, but theoretically it is not possible to predict how cells or organisms will react to a chemical substance.

As low doses of chemical substances are studied scientifically, more and more otherwise well-known substances are shown to have unexpected effects at low doses. Since the early 1990s, it has been clear that one cannot theoretically – based on a general dose-response formula – predict the response of cells to low concentrations of a substance.

In everyday life, we regularly experience that there is a linear relationship between dose and effect: Twice as much sugar tastes twice as sweet. Such is the case with the drugs and within the doses we normally use. The graph to the right shows 0-4 teaspoons of sugar in the coffee. It is the linear dose-response that we know best and that we often take for granted in daily life

From everyday life we also know of a decreasing effect on a larger dose. Double the dose of sugar in the coffee does not keep giving double effect. When the tongue’s sensation of sweetness is completely filled, an extra dose cannot be sensed. The body’s relationship to a variety of vitamins and minerals works in the same way. The graph to the right shows the experience of sweetness at 1-14 teaspoons of sugar in coffee.

Many substances first have a measurable effect above a certain threshold value as is known from e.g. alcohol. Below the threshold, no poisoning occurs – if you drink an alcoholic beverage with 7,5 ml or 6 grams of alcohol per hour, it has no effect, but if you drink an alcoholic beverage with 30 ml or 24 grams of alcohol per hour, you exceed the liver’s threshold value for continuously breaking down alcohol, after which alcohol continuously accumulates in the blood and you become drunk.

Some substances used as medicines inhibit processes in the body, so that higher doses inhibit the process more, but only within certain limits. With increasing dose, the inhibitory effect diminishes and eventually disappears. Well-known examples are statins, which lower the blood’s cholesterol content, and drugs that inhibit the stomach’s production of stomach acid.

Some drugs, including several hormones, have a bell-shaped dose-response curve. In addition to the fact that the substances are often active at very low doses, they are also only active within a “window”, so that they have a hormone-like or endocrine disrupting effect above a certain concentration, and then lose effect at higher concentrations. Several hormones and more proteins tested for cancer treatment have this type of dose-response (Reynolds, 2010; Diamond, 2004).

Some drugs have a U-shaped effect curve, so that the drug has a stimulating effect at low doses, but with decreasing effect at slightly higher doses, and then again has a stimulating effect at even higher doses. Several drugs with U-shaped dose-response curves are endocrine disruptors, or promote or inhibit cancer. (Almstrup et al., 2002; Davis & Svendsgaard 1990 and Vadenberg et al., 2012).

Living organisms – including humans – are extremely complex, and the “unexpected” types of non-linear toxic effects can e.g. is due to interactions where a chemical substance can affect sensors on or in the cells, immune reactions, enzymes in the liver, etc.,

In addition, the toxic effects of substances on humans can be determined by individual and often inherited genetic differences. For heavy metals such as mercury and copper, both individual differences and non-linear relationships are known (Andreoli & Sprovieri, 2017; O’Doherty et al., 2019).

In scientific research, organisms’ reactions to chemical substances are often assumed to be linear, so that researchers look for linear relationships without actually knowing if they are relevant. Non-linear contexts are also often overlooked in authorities’ risk assessments of substances. Overall, this means that researchers and authorities often disregard the toxic effects of substances on the basis of a rationale that when a clear toxic effect at low doses was not found at higher doses – well then one can simply ignore these results.

In the EU’s risk assessments of pesticides, GMOs, etc. one often disregards the concrete measurements or experiments that do not meet the requirement of linear and increasing toxicity at higher doses.

Not least Danish researchers such as Almstrup, Grandjean, Skakkebæk and Svendsgaard have helped to focus on non-linear dose response and toxic effects at low and extremely low doses. The same researchers are generally not impressed by the authorities’ ability or willingness to take this new knowledge seriously (Grandjean 2019, Hill et al 2018, Davis and Svendsgaard 1990); – neither is the Vitality Council.

Klaus Sall, cand.scient. in biology

References and further reading

Almstrup K; Fernández MF; Petersen JH; Olea N; Skakkebaek NE and Leffers H. (2002). Dual effects of phytoestro­gens result in u-shaped dose-response curves. Environ Health Perspect. 2002 August; 110(8): 743–748. LINK
Andreoli, V., Sprovieri, F., (2017). Genetic Aspects of Susceptibility to Mercury Toxicity: An Overview. Int J Environ Res Public Health 14. LINK
Davis JM og Svendsgaard DJ. 1990 U-shaped dose-response curves: their occurrence and implications for risk assessment. J Toxicol Environ Health. 1990 Jun;30(2):71-83. LINK
Diamond, D. M. 2004. Enhancement of Cognitive and Electrophysiological Measures of Hippocampal Functioning in Rats by a Low, But Not High, Dose of Dehydroepiandrosterone Sulfate (DHEAS). Nonlin. Biol. Toxicol. Med. 2004 Oct.; 2(4): 371–377. LINK
Grandjean, P., Abdennebi-Najar, L., Barouki, R., Cranor, C. F., Etzel, R. A., Gee, D., Heindel, J. J., Hougaard, K. S., Hunt, P., Nawrot, T. S., Prins, G. S., Ritz, B., Soffritti, M., Sunyer, J., & Weihe, P. (2019). Time scales of developmental toxicity impacting on research and needs for intervention. Basic & Clinical Pharmacology & Toxicology, 125(Suppl. 3), 70-80. LINK
Hill C. E., Myers J. P., Vandenberg L. N. (2018). Nonmonotonic dose-response curves occur in dose ranges that are relevant to regulatory decision-making. Dose Res. 16, 155932581879828. 1559325818798282–82. LINK
Lagarde, F., Beausoleil, C., Belcher, S. M., Belzunces, L. P., Emond, C., Guerbet, M., & Rousselle, C. (2015). Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment. Environmental health 14, 13 (2015), LINK
Montévil M, Acevedo N, Schaeberle CM, Bharadwaj M, Fenton SE, and Ana M. Soto AM. 2020. A Combined Morphometric and Statistical Approach to Assess Nonmonotonicity in the Developing Mammary Gland of Rats in the CLARITY-BPA Study. Environ Health Perspect. 2020 May; 128(5):57001. LINK
Reynolds, Andrew R. 2010. Potential Relevance of Bell-Shaped and U-Shaped Dose-Responses for the Therapeutic Targeting of Angiogenesis in Cancer. Dose Response. 2010; 8(3): 253–284. LINK
O’Doherty, C., Keenan, J., Horgan, K., Murphy, R., O’Sullivan, F., Clynes, M., 2019. Copper-induced non-monotonic dose response in Caco-2 cells. In Vitro Cell.Dev.Biol.-Animal 55, 221–225. LINK
Vandenberg et al. 2012. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses. Endocrine Reviews March 14, 2012 er.2011-1050 LINK
Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, Woodruff TJ, Vom Saal FS. Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society. Endocrinology 2012; 153:4097 – 110; LINK

Confusion about Omega-6

February 6, 2007

Confusion regarding the essential fatty acids is the rule rather than the exception while research regarding their good effects piles up. It’s hard to find head or tail in this subject, but the quick answer is: Eat more fish!

If you want to delve into the depths of this answer, then fasten your safety belt and read on!

There is general agreement that omega-3 fatty acids have a high health value in all of their sources, from linseed oils alpha-linolenic acid to fish’s docosahexaenoic acid and prostaglandin E3.

Is this true about the omega-6 fatty acids?

There is common confusion about the health benefits of essential fatty acids, and this has not been reduced by recent public warnings against the use of polyunsaturated omega-6 fatty acids.

Let’s look into this:

The most common misconception is that it is possible to generalize about all omega-6 fatty acids. It is not. In the industrialized world the problem is that we are inundated with cheap linoleic acid, which is an omega-6 fatty acid that is found in e.g. corn and sunflower oil. Linoleic acid alone is not that healthy either. If you eat too much of it, you build up deposits of NEFA (which has nothing to do with bicycle lights!) but means that linoleic acid builds up as a non-esterized fat, which can lead to sudden cardiac arrest (1).
The ratio between our consumption of omega-6 to omega-3 fatty acids should be close to 2:1, but unfortunately it is closer to 20:1. The problem with linoleic acid is that we get too much of it because it is cheap.

Linoleic acid must be converted to gamma linolenic acid (GLA), followed by DGLA and prostaglandin E1, before we have the equivalent of healthy omega-3 fatty acids. The first conversion (to GLA) requires an enzyme called delta-6-desaturase. There are many people this enzyme. These people are primarily people with allergies and people with diabetes. When you lack this enzyme the only way to avoid getting too much linoleic acid is to take supplementary GLA. GLA is found in evening primrose oil or borage seed oil.

If you do not lack delta-6-desaturase, the best thing to do is to limit linoleic oil intake and increase fish oil consumption.

If we eat fatty fish and fish oil we save more of the enzyme needed to convert linoleic acid to GLA. Therefore, if we balance our linoleic acid consumption with fish oil then we will not suffer as many harmful effects from unconverted omega-6 fatty acid.

Another way of reducing the amount of accumulated linoleic acid is by taking the amino acid L-Carnitine. L-Carnitine functions as a kind of oil pipeline which transports the linoleic acid directly into the cells power plant (the mitochondria), where, with the help of Q10, it is made into energy. This reduces the amount of freely circulating linoleic acid in the blood.

As explained in the above, we should avoid too much linoleic acid, whereas its converted product, GLA, is healthy and good. So the health value of omega-6 fatty acids is dependent on which omega-3 fatty acid is being discussed.

In a large summary article in Current Pharmaceutical Biotechnology (2), the authors assess a long list of illnesses where GLA has an amazing effect. These include inflammatory conditions such as rheumatoid arthritis, autoimmune diseases, and cancers. GLA has been shown to be able to inhibit osteonectin, which is a protein connected cancer metastasis. GLA also has been shown to increase nerve impulse speed in diabetics.

Therefore, omega-6 fatty acids cannot be seen as either all bad or all good. This is especially true when comparing GLA with linoleic acid. Supplementation of both fish oil and GLA is a good idea.

By: Vitality Council

References:
1. Circulating Nonesterified Fatty Acid Level as a Predictive Risk Factor for Sudden Death in the Population. Xavier Jouven, MD, PhD; Marie-Aline Charles, MD; Michel Desnos, MD; Pierre Ducimetière, PhD. Circulation. 2001;104:756.
2. Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. Kapoor R, Huang Y-S, Current Pharmaceutical Biotechnology, 2006; 7(6): 531-4.

Remember your daily egg

November 28, 2006

Two new studies indicate that important nutrients, contained in, among other things, egg, play a part in the prevention of the most common type of age related blindness.

Macular degeneration, otherwise known as retinal calcification, is the degeneration of retinal cells in the eye’s macula (a yellow spot in the middle of the eye which is the centre of the visual field and has a high concentration of cells responsible for colour vision). Because the macula is in the centre of the eye, if one looses cells in the macula, one also looses sight in the centre of the eye. This means that peripheral vision is retained. With macular degeneration, it is possible to become oriented in, for example, a room, but it is difficult to see what lies directly ahead, including faces, the TV, or a newspaper. One retains ones sense of space, but is functionally blind. It is very irritating for sufferers because they cannot recognize their children or close friends it they meet them on the street. They cannot see their faces, only a black dot.

The first sign of macular degeneration is that straight lines aren’t seen as being straight, but bend so that text and the blinds in front of the window “bulge.” The next sign is the loss of colour vision, because the macula has the highest concentration of colour discerning cells (cones) in the eye.

Earlier studies have shown that it is possible to reduce the risk of macular degeneration with certain antioxidants. Recent studies are interesting because thy have shown that natural measures can be used to in increase the retina’s contents of important chemicals, thereby decreasing the risk of macular degeneration.

At the University of Wisconsin in Madison, USA, an analysis of 1,700 older women from the huge Women’s Health Initiative (a study over what it now a period of 15 years including 161,000 women of the ages 50 – 79) showed that their density of macula pigment was positively correlated with the amount of carotenoids such as lutein and zeaxanthin in the diet and negatively correlated with diabetes and obesity.

A coinciding intervention study was undertaken at the University of New Hampshire, USA, where a group of 24 women, aged 24-59, ate 6 eggs weekly over a period of 12 weeks.

Both lutein and zeaxanthin is found in eggs yolks from which they are readily absorbed into the blood and thereafter concentrated in the retina.

One group received eggs with 331 micrograms lutein and zeaxanthin per yolk. Another received eggs with 964 micrograms lutein and zeaxanthin per yolk and a third group received a daily sugar pill, which they were told contained lutein and zeaxanthin.

I both of the groups which ate the daily egg their levels of lutein and zeaxanthin increased. The same was not true of the group which received the sugar pill. This effect was known from earlier studies with eggs, but this study went one step further and measured the participants density of macula pigment as well as serum – cholesterol and triglycerides at the start of the study and after 4, 8, and 12 weeks.

Serum – cholesterol was not increased in either of the groups which received eggs, but both cholesterol and triglyceride levels increased significantly in the participants who received sugar pills.

Conversely, serum zeaxanthin (not lutein) as well as, importantly, the retina’s content of sight pigment increased in the eggs groups, but not in the sugar group.

Even though there are significantly more carotenoids in vegetables, such as spinach, the authors of the study prefer eggs because of their high bioavailability of lutein and zeaxanthin.

It is nice to, one more time, establish that eggs are good. And they don’t taste too bad either!

By: Vitality Council

References:
• Mares JA, Larowe TL, et al. Predictors of optical density of lutein and zeaxanthin in retinas of older women in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women’s Health Initiative. Am J Clin Nutr., 2006, 84(5): 1107-1122.
• Wenzel AJ, Gerweck C, et al. A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women. J Nutr., 2006; 136(10): 2568-2573.

www.ajcn.org
jn.nutrition.org/contents-by-date.0.shtml

Fish oil is good for the heart and the brain

August 21, 2006

There is no doubt that fish oil is good for the heart. This has been shown by a new extensive survey on the subject. But no one knows how much is ideal.

The scientific interest for fish oil is enormous. Since September of last year, almost 800 articles about fish oil have been publicised in established journals.

This is with very good reason. Notably, fish oil contains two types of fatty acid, both of which are attributed with having a positive effect against many serious chronic diseases. If this is even in part true, it should be considered very imprudent not to receive fish oil every day. The primary disease that it is believed to prevent is cardiovascular disease, but there is also good reason to believe that fish oil works against, for example, depression, dementia, arthritis, and diabetes, even though there is no concrete evidence as of yet in these areas.

The two fatty acids are called EPA (eicosapentic acid) and DHA (docosahexa-enoic acid). Together they compose one third of the contents of fish oil and two thirds of the concentrated fish oil products, which can be found in capsule form.

Much attention has been given to DHA which, contrary to EPA, is found in large amounts in the brain (14% of the cerebral cortex’s fat content) and in even greater amounts in the retina (22%). Breast fed children have much higher concentrations of DHA in their brains than bottle fed children (babies cannot produce DHA themselves). It is hard to believe that there are no consequences of receive too little.

There are an incredible number of adults who take supplements of fish oil daily to maintain their cardiac health.

But does it work?

Six months ago a group of English researchers maintained that it does not. They had looked at all of the relevant studies and then calculated the averages of their results. In their opinion, the results showed that fish oil neither protects the heart nor lengthens life span. This is just the opposite of what was previously believed.

This meta-analysis was strongly criticized and, as discussed in another of The Danish Vitality Council’s newsletters (“Fish Oil – Still indispensible”) there were so many question raised by the analysis that it lacked credibility.

Doubts regarding the dosage
This is now supported by a summary article from the distinguished American Journal of Clinical Nutrition. According to the head authors, a group of researchers undertook an extensive survey, taking “a large step forward” in spreading light into the darkness. There is no longer much doubt that fish oil reduces the overall risk of premature death and the risk of death due to a blood clot in the heart, and that it possibly reduces the risk of stroke.

Completing this survey was an extensive project. The researchers first read summaries of 8,039 scientific articles. They then picked 842 relevant articles from these to be read in their entirety. 46 articles of these 842 met the strict quality requirements and were studied further. The researches requirements regarded the length of the studies (at least one year), the dose of the fish oil given, and proper documentation.

How big are the advantages and how much fish oil should one take? This actually cannot be answered with certainty! The studies surveyed were too different regarding the dose given, the type of participants, the time taken, and so on to answer such questions. It is simply bad form to establish any averages, as the English researchers did. But if one wants to draw conclusions anyway, it is safe to guess that the overall risk of premature death and the risk of death due to cardiac disease can be reduced by 15-20% or more.

It is however nearly certain that fish oil helps those who have had a blood clot in the heart and wish to avoid another. But what about the dose, how much should one take?

Until more information surfaces, we should rely on the American Heart Association’s recommendations, which are based on estimates. Heart patients should receive 1 gr. EPA + DHA daily. This is the equivalent of about two large capsules of 1 gr. concentrated fish oil. Everyone else should receive at least half this amount. This can be achieved by eating fatty fish for dinner 1-2 times weekly.

There is a lot of knowledge lying in wait, not just about fish oil and the heart. More results will surface in the next year. While we wait we wait in the knowledge that it is important to get enough.

By: Vitality Council

References:
1. Wang C et al. n-3 fatty acids from fish or fish-oil supplements, but not á-linolenic acid, benefit cardiovascular disease outcome in primary- and secondary-prevention studies: A systematic review. Am J Clin Nutr 2006;84:5-17.
2. Deckelbaum R et al. n-3 fatty acids and cardiovascular disease: navigating toward recommendations. Am J Clin Nutr 2006;84:1-2.
3. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr 2006;83(suppl):1467S-76S.

www.ajcn.org

Children with ADHD lack magneisum

March 17, 2006

A majority of restless ADHD children were lacking in magnesium. All children improved when given magnesium and B6-vitamin supplements.

In almost all kindergarten classes there are one or two so-called ADHD-children giving the teacher a hard time with their continuous restlessness, running about, violent behaviour and inattentiveness. (ADHD stands for Attention Deficit, Hyperactivity Disorder).

Two studies – the only ones conducted – have now shown that a combination of magnesium and vitamin B6 helps.

Why should magnesium help? In a French study 52 children, all diagnosed with ADHD, were examined. The children were typically six years old. If the serum level of magnesium was measured in a normal blood test, normal values were seen. But since almost all magnesium in the body is found inside the cells, this says nothing. It is inside the cells that we must look.

On average, the children only had 4/5 of the amount of magnesium in the cells (in this case, the red blood cells) present in normal adults. They were deficient in magnesium!

Therefore they were given a daily supplement of 6 mg. of magnesium and 0.8 mg. Vitamin B6 per kilo body mass for one to six months. After this, no less than all the children got better. For example, at the beginning of the experiment 26 of the children were deemed physically aggressive. After four months, only six. At the same time their ability to concentrate and their attention span improved (evaluated in an approved manner). Statistically, these results were quite credible.

A weakness in the French study was that it was a so-called open study. There was no untreated control group and the treatment was not blind. This leaves room for coincidence and over-interpretation. On the other hand, the study showed exactly the same as a similar study from 1997. Also, the improvements occurred at the same time as the measurable magnesium deficiency disappeared. When this had happened, treatment was stopped.

Magnesium in the Diet
If it works, it may not be that surprising. The same course of treatment seems to have helped women suffering from irritability and imbalance due to PMS (PreMenstrual Syndrome) in several studies. On top of this comes the generally sedative effect on nerves (magnesium can be used as a local anaesthetic). Magnesium has a relaxing effect on muscles. Does magnesium also have a calming effect on the central nervous system?

Another question is why ADHD-children apparently are deficient in magnesium. The French suggest that genetic factors play a role, but in a majority of the parents, it was not just one, but both of them who were deficient in the mineral. This suggests that nutrition is more important.

A British evaluation indicates that foodstuffs’ content of magnesium has decreased in the past 60 years. It is estimated that today there is 24 and 16 percent less magnesium in vegetables and fruit, respectively, than in 1940. On top of this is an increase in the consumption of sugar. Those who dauntlessly claim that 10 percent of the calories in the diet can be contributed by sugar, are also saying that you can easily omit 10 percent of the diet’s magnesium. Furthermore, less physical work means a decreased need for food generally, thereby decreasing the amount of magnesium we consume. A typical magnesium consumption rate today (3-400 mg. a day) is probably half of what it was 100 years ago.

Something else to consider also is that there is a row of more or less confirmed observations of connections between behavioural disorders in children and teenagers (and criminals) and an unhealthy diet. Is this purely coincidence?
It will take several months to rectify a magnesium deficiency, but it might be worth it to try.

By: Vitality Council

References:
1. Mousain-Bosc et al. Magnesium VitB6 intake reduces central nervous system hyperexcitability in children. J Am Coll Nutrition 2004;23:545S-548S
2. Starobrat-Hermelin et al. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactive disorder (ADHD). Magnes Res 1997;10:143-8

www.jacn.org

Antioxidants against macular degeneration and blindness

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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jama.ama-assn.org

Glusosamine is more that just glucosamine

March 2, 2006

Watch out. Read the declaration carefully, when you buy Glucosamine for your osteoarthrosis.

According to a new research study, Glucosamine did not help against osteoarthrosis of the knees. According to another study, glucosamine was so beneficially, that it ought to be standard treatment. Its important to know, that the Glucosamine in the two studies were not the same type.

If you are to believe the publicised GAIT-study, it is meaningless to take glucosamine for arthritis of the knees. It just doesn’t work.

The GAIT-study was both large and thorough. It encompassed 1,583 patients with arthritis and lasted for 24 months. The participants were on average 53 years old and 2/3 of them were women.

These many arthritis patients were organised into six groups by lottery. These groups receive the following treatment:

  1. 1,500 mg glucosamine daily
  2. 1,200 mg chondroitine sulphate (which is like glucosamine) daily
  3. A combination of the two first treatments
  4. 200 mg of the prescription medicine Celebra
  5. Placebo

No one knew what they received and all of the participants answered detailed questions about their pain, stiffness, walking distance, and so on before and after the 24 weeks. Each participant then received a score based on their answers which indicated the severity of their symptoms.

The goal of the study was to find out how many of the participants showed a 20% improvement after the 24 weeks, but the results were surprising. No fewer than 60% of those who received the placebo had a 20% or better improvement. The results were only slighty better in the other groups: 64% for the glucosamine group, 65% for the chondroitine sulphate group, 67% for the combination group, and 70% for the group taking the prescription medication. Only the last group differed from the placebo group enough to be statistically significant.

The combination treatment did work for a small group (354 of the participants) who related mild pain after the treatment as opposed to moderate-strong pain. 80% of these people were (at least 20%) better off.

But the glucosamine alone was not better than the placebo.

Protects the cartilage
Another study called the GUIDE study was presented in November at the yearly meeting of The American College of Rheumatology. It included 318 patients (88% women) who also had arthritis in their knees. They received daily supplements of:

  1. Placebo
  2. Glucosamine (1,500 mg per day)
  3. Paracetamol (1 gr. three times daily)

This study also lasted a half year, but this the groups which received paracetamol and glucosamine reported an improvement of 30% more than the placebo group, even though the study was structured the same way as the GAIT-study. There was also a tendency that the glucosamine was better than the pain relieving paracetamol.

Why was there such a large difference between GAIT and GUIDE? This can possibly be explained by an editorial in the New England Journal of Medicine, which originally published the GAIT-study.

The difference could be that glucosamine-hydrochloride was used in the GAIT study whereas GUIDE used glucosamine-sulfate. Sulfate is crucial for the effectiveness of glucosamine.

Two randomised studies have shown that glucosamine-sulfate puts the breaks on the development of arthritis in the knees. This could be proven using X-ray photographs.

Glucosamine sulphate counteracts the breakdown of cartilage!
The New England Journal of Medicine editorial comment on the GAIT study related the following: “Arthritis patients who wish to take dietary supplements… should… take glucosamine-sulfate, not glucosamine-hydrochloride.” The lead author of the GUIDE-study stated that, “1,500 mg glucosamine-sulfate once a day could become the preferred treatment for arthritis in the knees.” The studies ended differently, but their recommendations are the same!

So read the label carefully.
It should read: “500 mg Glucosamine-sulfate, corresponding to 400 mg Glucosamine.”

By: Vitality Council

References:
1. Clegg DO et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006 Feb 23;354(8):795-808.
2. American College of Rheumatology Annual Scientific Meeting in San Diego, California. Press release.

content.nejm.org

Calcium supplements with vitamin D against colon cancer?

February 18, 2006

A large study attempted to show whether or not calcium and vitamin D prevent colon cancer. It was a strange study, using low doses over a short period.

There are probably those who believe that the latest study on calcium and vitamin D shows that neither is good for anything. But we should hesitate before going to that extreme. One can also believe that the study was not suited to draw this conclusion. Or, as it is stated in a leading editorial in “The New England Journal of Medicine:” the conclusion should be interpreted in light of the study was complicated and in light of the probability that the doses of calcium and vitamin D were too low.

The debate regards the insidious and widespread cancers of the colon and rectum. Half of a group of 36,282 American women between the ages of 50 and 79 took part in a seven year study where they received daily supplements of 1,000 mg calcium and 400 units vitamin D to see if reduced their risk of these diseases. The supplements given are the same as two normal calcium and vitamin D vitamin tablets, which many take to strengthen their bones. After the seven years the researchers assessed the number of women who developed colon and rectum cancer. The result was disheartening: Whether the women received supplements or placebo had not effect on the risk.

There was a single positive find buried in the data. The women who had the least vitamin D in their blood during the study had with statistical certainty the greatest probability of developing colon cancer. This could indicate that vitamin D has a positive effect. There was also a tendency, but only a tendency, that these women had the greatest benefit from the supplements.

Quite a lot of things contribute to that this conclusion be taken with a grain of salt. This is partially due to that the study was very complex.

Possibly the most important objection is that it “only” lasted seven years. It is believed that colon cancer takes 10-20 years to develop before it is diagnosed. It the supplements prevent a new cancer from forming it is clear that for this reason no effects will be found as early as after seven years. This has been considered: Participants in the study will be monitored further for the next five years.

Strong objections
If the goal was to show a difference within the seven year period, those responsible should have at least ended the study by examining the intestines of all of the participants in order to find early cancer stages, or polyps. This did not occur. There was neither the money nor the resources necessary to do over 35,000 intestinal examinations. It was only possible to establish that the number of independently undertaken intestinal exams and the number of discovered cancers in the two groups were about the same. But maybe nothing more can be expected.

One confusing detail is that the study participants were allowed to continue taking the supplements that they had taken before the study along with the supplements that they received as a part of the study. On average they received 1,100 mg calcium and 350 units vitamin D, both close to the recommended dosages, before the study began. Many of them therefore must have received very large doses of calcium, over 2,000 mg, per day. Is it reasonable to guess that this is the reason for the slightly increased frequency of self-reported kidney stones? 2.4% of those who received supplements and 2.1% of those who received placebo, got kidney stones during the seven years.

Also, the average age was relatively low (62), which reduced the risk of cancer, and therefore weakened the study. It was further weakened by the fact that more than one out of four participants did not finish the study. Whether this dropout rate is because calcium pills can cause constipation is not considered in the article.

Just as important, the dose of vitamin D, as referred to in the editorial, may have been too low. Recently it has been estimated that about 1,000 units daily is necessary for most people in order to achieve any supposed cancer preventing effect. This amount of vitamin D (or more accurately 25-(OH)-vitamin D) is necessary to achieve a serum concentration of over 30 nano-grams per litre (75 nanomols per millilitre). Nevertheless, only a minority of the study participants received this amount.

What can be concluded from this? The editorial gives some suggestions for new studies. Much indicates that vitamin D, and maybe calcium, prevents cancer. But we still lack sufficient knowledge.

By: Vitality Council

References:
1. Wactawski-Wende J et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006;354:684-96.
2. Forman M C et al. Calcium plus vitamin D3 supplementation and colorectal cancer in women. N Engl J Med 2006;354:752-4.
3. Garland C F et al. The role of vitamin D in cancer prevention. Am J Publ Health 2006;96:9-18.

By all Means: Enjoy a great Sauce!

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.

Greater need for vitamin B-12

February 1, 2006

Middle-aged and elderly women’s need for Vitamin B-12 is with great certainty 2,5 times higher than previously believed. A daily vitamin tablet is often not enough.

How is the need for a vitamin determined? Earlier it was determined based on how much is necessary to avoid acute deficiencies. This is sometimes still the case. For example, the current recommendations for vitamin C are still based on a World War II study on 20 English military objectors. Half of them came down with scurvy and two were close to death. But this study found that scurvy can be avoided with 12 mg vitamin C per day.

This kind of research is brutal by today’s standards. But it is also antiquated because it does not take other deficiency symptoms into account, including those which arise after longer periods and are not coupled with bruising of the skin, brittle bones, paralyses, and other acute symptoms. Today, instead of merely recording with a study participant becomes deathly ill, we follow the processes that the vitamins in question are involved in and determine whether or not they function as they should. This methodology was used by the American, Mark Levine when he proved that our need for vitamin C is closed to 200 mg per day than the normally recommended 60 mg. If one makes due with 60 mg it is believed that the vitamin C dependant reactions become slow and that there is an significantly increased risk of cardiovascular disease and cancer.

Of current interest, there is news regarding the need for vitamin B12. The current recommendation in England has been set to 1 microgram per day. A Danish study has recently shown that the need for vitamin B12 is six times as much (6 micrograms). This was determined in a study of 98 Danish women with an average age of 60. Such a large need meanwhile created a problem; the women typically only received 4.6 micrograms via their diet.

Even though they supplemented their intake with a normal vitamin pill (1 microgram B12), half of them received too little vitamin B12. Stronger pills are needed.

Increasing recommendations
For the last 50 years B12 status has been determined by measuring the blood’s B12 content. Findings in recent years have shown that a “normal” B12 value does not necessarily mean that there is enough. Even with a normal B12 value, build op of metabolism products which B12 normally removes can occur (these include homocysteine and MMA, otherwise known as methylmalonic acid). Therefore the amount of these substances present is measured when trying to determine whether or not there is a deficiency.

Recently a third indirect measure for B12 deficiency has been put into focus: holotranscobalamin, a B12 containing protein, seems to be able to replace the above-mentioned method and may even be more sensitive to B12 deficiency. It is very important to get enough of this protein. It is responsible for delivering B12 to the cells, almost like the paperboy who delivers the paper to your door. Without the paperboy, there is no paper.

The Danish study showed that the values for Holotranscobalamin, MMA, and homocysteine no longer indicated deficiency only when a B12 intake of over 6 micrograms per day was achieved. If B12 intake is less than 6 micrograms, there is sand in the B12-works.

The researchers conclude with conviction:
”…our results, together with those of others, strongly suggest that the RDA of 2.4 micrograms/day should be increased.”
This can also been said about many other vitamins. Experience from recent years indicates that the recommendations for not only vitamin B12, but also vitamins C and E and the minerals selenium, chromium, and magnesium, should also be increased, and in some cases greatly increased. Increased intake of many of the other B vitamins as well as iodine should also be considered.

This is especially true about vitamin D, on which we at the Danish Vitality Counsel have focused. The recommended daily dosage of vitamin D should be doubled for those of us who live in northern climes.

The official recommendations have as a whole not followed developments in research, even though there are strong arguments for new recommendations. According to some, there is need for more evidence. But this is contrary to the supposition that new recommendations could prevent serious chronic disease.

The dilemma is strengthened by the fact that it is difficult or impossible to get higher doses of vitamins and minerals though our modern diet. Some suggest that it might be possible with a Stone Age diet, but we surely will not have another Stone Age.

By: Vitality Council

References:
1. Mustafa Vakar Bor et al. A daily intake of approximately 6 {micro}g vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women. Am J Clin Nutr. 2006 Jan;83(1):52-8.
2. Zouë Lloyd-Wright et al. Holotranscobalamin as an Indicator of Dietary Vitamin B12 Deficiency. Clinical Chemistry 49: 2076-2078, 2003;10.1373/clinchem.2003.020743.

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