Category: Enzymes / Vitamin-like substances

Patent or not, that is the question

Claus Hancke

November 16, 2023

Is it really necessary to have a patent and billions of kroner before the media takes an interest in sensationally good results?

The other day in the newspaper Politiken, you could read an article (1) about Ozempic and Wegovy /Semaglutide, including an interview with Professor Jens Søndergaard, who stated that a recent study from the Cleveland Clinic had shown a 20% reduction in serious cardiovascular events after 4 years of treatment, which is such a great medical breakthrough that he had never seen anything like it, and compared it to the discovery of penicillin. -This is really great.

Semaglutide costs DKK 2,400 per month and has side effects in the form of upset stomach and nausea.

The result is quite impressive, even if it is a relative risk reduction rather than an absolute risk reduction. But there are now other scientific studies from this year that have shown far more impressive results.

What if there were a treatment that after 4 years showed a reduction in cardiovascular mortality of over 50% at a price of DKK 369. per month and completely without side effects? … What??
Yes, that is precisely the conclusion of the 10-year follow-up of the 2013 study (2) of Selenium and Coenzyme Q10 in combination.

The study (3) was previously described in the Vitality Council’s newsletter of 23 April 2023. However, that is not what I want to focus on here. It is rather the selection of news in the media that I want to discuss.

What really surprises me is that a risk reduction of 20% for cardiac events draws huge headlines and benevolent admiration whereas an equally valid study, which even shows a reduction in cardiovascular mortality of over 50%, is not even mentioned in the same newspapers -and you can’t deny the quality of this study.

Is it because it’s too good to be true that the media don’t want to bother writing about the scientific article, or does it absolutely have to be an expensive prescription drug with side effects before it’s interesting?

Actually, Professor Urban Alehagen also doubted his own results, which is why he analyzed them again and again from different sides but came to the same result.

And he is not the only one, as numerous previous studies have shown consistent increased survival with selenium and/or Q10.

Senior physician Svend Aage Mortensen at Rigshospitalet published several fine studies (4) of Q10 against heart failure but without their winning any resonance in the very orthodox medical profession.

Substances such as Coenzyme Q10 cannot be patented. Is that where the dog is buried? After all, a patent opens up possibilities for absolutely exorbitant earnings and the resulting marketing, press coverage, etc., just as there are funds for further research, publications, press, etc. -A self-reinforcing wheel that just goes faster and faster.

Substances that cannot be patented easily drown in the media stream because there is no great interest when there is no big money involved. But that is precisely why one should be even more interested in the serious research that takes place with these unpatented products. Professor Alehagen’s studies have clearly shown that an expensive, patented product is not necessary to halve the risk of dying of cardiovascular disease.

It is simply incredible that the selenium and Coenzyme Q10 study has not found a place on the front pages of the media.

Take care of yourself and others.

Claus Hancke MD
Specialist in general medicine

Refs.

  1. Politiken 13/11-2023
  2. U Alehagen et al. Int J Cardiol 2013;167:1860-1866.
  3. U Alehagen et al. Antioxidants 2023, 12, 759
  4. https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1002/biof.5520180210

More is not always better

Klaus Sall

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

An end to the old weakling

Claus Hancke

July 14, 2006

The deficiency of an important antioxidant enzyme seems to be the most important reason that the elderly develop weak muscles. This paves the way for interesting perspectives.

The most striking sign of aging is that muscle strength is reduced and movement becomes slower. Even the most persistent exerciser cannot avoid it. The weakening of the muscles is the most important reason that old people become frail.

Why does this happen? We know that with age more and more signs of oxidation by free radicals can be found in muscles and other tissue. But is this why the muscles weaken?

A group of 12 researchers from both Texas and Stanford University in U.S.A. have undertaken an unusual and very detailed study which indicates that this is precisely the reason. According to them, the age related muscle weakness is due to strain from free oxygen radicals. This can shine light on possible ways to slow this process and maintain mobility longer.

Aging mice are a reliable model for age related muscle weakness in humans. But the American study was just possible because they had a special genetically manipulated mouse which lacked the ability to produce SOD (superoxide dismutase), a very important anti-oxidative enzyme.

In order to understand this it is necessary to know that free radicals are broken down in a chain reaction. SOD is necessary in the first step. In this step “active oxygen” (superoxide anions) is converted to less dangerous hydrogen peroxide. Without SOD this occurs very slowly, but with SOD this occurs at breakneck speed. In the next step hydrogen peroxide, which is also dangerous, is converted to harmless water. This occurs with the help of a selenium rich enzyme. This is one of the best known reasons that selenium, which we get too little of, is necessary for life.

Vital SOD
Back to SOD. It is also necessary to know that there are many forms of SOD. One of them is found in the mitochondria, which are the small power plants of the cells where cell metabolism occurs. If a mouse lacks SOD here, it dies after no more than three weeks. The power plants are destroyed by the free radicals which they produce. Another form of SOD is found outside the mitochondria, but still inside the cells. If the mice lack this type they can survive, but their lifespan is shortened by about 30%.

The researchers worked with mice which lacked the latter SOD form. They saw that the mice already started to develop weakened muscles while young. When the mice were 29 months old, they lacked half of their muscle mass in their hindquarters, whereas normal mice of the same age retain all of their youthful muscle. The so called fast type II muscle fibres were the most affected. The mice were left with slower type I fibres. Heart muscle remained undamaged.

The strength and speed of the muscles were not the only things affected. The mice also became less curious and less willing to engage in exhausting exercises like running in a mouse wheel. When they become old, they shook slightly in their weakened muscles.

It is hard to contest that this damage was caused by oxygen radicals. SOD has no other function other than being an antioxidant. As always it can be added that more research is necessary. This was only a study on mice. But if the results can be transferred to humans it can be argued that it is beneficial to increase the body’s production of SOD. SOD production is decreased with age.

Because SOD is an enzyme, which is to say a protein, it cannot be eaten without being destroyed in the stomach unless given as a special preparation. In combination with other antioxidants and possibly vitamin D (but that’s another story) the effect is supposedly more pronounced. This is not certain, but it is interesting.

By: Vitality Council

References:
1. Muller, Florian L et al. Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy. Free Radical Biology & Medicine 2006;40:1993-2004
2. Jackson Malcolm J. Lack of CuZnSOD activity: A pointer to the mechanisms underlying age-related loss of muscle function, a commentary on “Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy”. Free Radical Biology & Medicine 2006;40:1900-01

New Type of Antioxidant Protects Against Sunburns

Claus Hancke

June 6, 2005

A new type of antioxidant protects against sunburns and is thought to have other, additional health benefits. Similarly, vitamins C and E have been found to work too.

French researchers have created an innovative substance, incorporating a special form of the important antioxidant/enzyme SOD (Super Oxide Dismutase), that can be taken orally without fear of the SOD being destroyed in the stomach prior to assimilation.

The human body itself creates SOD, an essential enzyme. So far, it has only been possible to supply SOD by injection. But thanks to a combination of the enzyme with the wheat protein gliadin, this difficulty has now been overcome. The product (Glisodin) can be bought in Denmark.

By. Vitality Council

(Shortened)

References:
1. CARD (Annual Congress of Dermatological Research) meeting in Brest on May 28th 2005, (report).
2. Placzek M et al. Ultraviolet B-induced DNA damage in human epidermis is modified by the antioxidants ascorbic acid and D-alpha-tocopherol. J Invest Dermatol. 2005 Feb;124(2):304-7.
3. Bialy TL et al. Dietary factors in the prevention and treatment of nonmelanoma skin cancer and melanoma. Dermatol Surg 2002;28:1143-52.

www.blackwell-synergy.com/loi/jid
www.blackwellpublishing.com/journal.asp
www.iom.dk

Carnitine, a Stimulant for Heart, Brain, and Muscles

Claus Hancke

May 9, 2005

Carnitine creates energy in aged cells. The message from a new scientific congress is that supplementation of carnitine seems to help against both heart disease, arteriosclerosis, and dementia.

Are your memory failing or are you loosing strength, then perhaps carnitine is the remedy for rescue

Carnitine is an – undeservedly – overlooked dietary supplement that is on its way into the ‘scientific warmth’. A clear signal is that the New York Academy of Sciences dedicate a whole volume of its famous scientific annals to carnitine alone.

Here you can read more than 197 pages from all 18 contributions given at a two-day conference on carnitine held by the academy in March 2004. The contributions are, among other things, about the importance of carnitine for the burning of fat, for the functioning of the muscles and the heart and about its promising role in the fight against a weakened memory.

………………………

By: Vitality Council

Reference:
Salvatore Alesci et al. (Eds.). Carnitine: The Science behind a Conditionally Essential Nutrient. Annals of The New York Academy of Sciences 2005, vol. 1033.

www.annalsnyas.org
www.iom.dk

Perhaps Prostate Cancer may be a Rarity in the Future

Claus Hancke

April 1, 2005

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

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

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

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

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

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

By: Vitality Council

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

www.aacr.org/cncrrea.htm
www.ingentaconnect.com/content/klu/caco;jsessionid=2sf53q49osdn1.victoria
www.iom.dk

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
www.iom.dk