Association Française d'Anti-Aging

PREVENTION IS THE BEST CURE

CLAUDE DALLE — 2007-11-04T16:28:22Z

1096 words Sent Editorial Board 18.7.05

Prevention is the best cure: a 21st century prospect

by Luc Montagnier, M.D.*

Citizens of developed countries have enjoyed in the last century a continuous increase of their life expectancy. This is largely due to advances of modern medicine and improvement of well being. The trend is continuing now, although to a slower pace. Together with the reduction of birth rates, the resulting age distribution is leaning towards an increased percentage of people over 65, 30% or more in the coming decades. However, more and more chronic diseases are crippling this ageing population: cancers, arthritis and arthrosis, cardiovascular and neurodegenerative diseases bring more people to hospitals and retirement boarding houses. The improvement of medical care and of early diagnostic methods does not suffice to explain this spectacular increment: the incidence of brain tumours increases, and there is now in Europe five more times cases of Alzheimer disease than fifty years ago.

We should ask: is it an inescapable evolution linked to aging or are there medical solutions enabling us to counteract it ? In other words, can we leave healthy longer until we meet the genetic limitations of our life span ? I believe this is possible if the concept of preventive medicine enters our mind and if we act accordingly. Prevention campaigns have already shown their efficacy in reducing in men (not in women) the incidence of lung cancer induced by tobacco smoking. They are still too timid in combating bad nutrition habits leading to obesity, especially in children. Changes in behaviour need to be reached early in life, by education in high schools.

But preventive medicine should go far beyond, by trying to find the roots of chronic diseases. Their causes are multiple, some of them are depending on global environmental changes, which can only be controlled by measures at the global level: atmospheric and food pollution, increase exposure to radiations, occurrence of new infectious agents. But at the individual level, there is a common biochemical denominator resulting from the summation of genetic, behavioural and environmental factors: oxidative stress, which is defined by an unbalance between an excess of reactive oxygen species (ROS) and the antioxidant defences.

There are intrinsic factors for the generation of ROS: dysfunction of mitochondria, thymic involution favouring chronic inflammation and infections. In fact, recent studies indicate that some degree of oxidative stress as measured by a deficit in reduced thiol groups or by an increase of peroxidized lipids, does occur in all aging people, even in a healthy state. However it is much more pronounced in patients with chronic diseases, particularly with Alzheimer and Parkinson diseases. Linked with oxidative stress, there is a dysfunction of the immune system, which bears particularly on cell mediated immunity and on a shift from TH1 to TH2 responses: auto-immune reactions and expansion of latent micro-organisms will ensue, increasing oxidative stress and causing irreversible damages in cells and organs.

Two lines of research can bring up solutions: (i) to re-establish a normal redox status by appropriate supplementation of antioxidants, (ii) to reduce the role of chronic infection by micro-organisms. Up to now the use of antioxidant supplements (Vitamin C, Vitamin E) has been erratic and often not medically controlled, leading to counteracting, pro-oxidant effects and discouraging the medical community to learn more about this field. In fact, time has come for the rational use of antioxidative regimens, adapted to each person (there is gene polymorphism of our antioxidative enzymes), and monitored by measurements of parameters of oxidative stress in blood or urine (peroxidized lipids, oxidized DNA bases, level of reduced glutathion, etc.).

Rather than chemically synthesized products, natural mixtures (herbal) of antioxidants are likely to be the most efficient, their efficacy being assessed first by controlled clinical trials. At advanced stages of diseases, where irreversible damages have occurred, we can only hope a delay or stabilization of further deterioration by the restoration of a normal redox status, this benefit being added to that of classical specific treatments (including perhaps in the future stem cell regeneration). But the best use of antioxidative treatment will be a preventive one, before occurrence of disease.

The postulate, but this is a likely postulate, is that if someone has strong oxidative stress in his middle age, he is at risk of suffering later of cancer, diabetes, arthritis or neurodegenerative disease. Therefore an appropriate regimen (food + supplements) should be prescribed until biochemical monitoring shows disappearance of oxidative stress. Of course, this approach will be symptomatic and will not address the causes of potential diseases. Although we cannot act on the built-in factors (mitochondrial ageing, thymus involution) we may address the role of latent infections, particularly bacterial infections.

There are already examples of neurodegenerative diseases caused by the ingestion of bacterial neurotoxins, and the role of chlamydia and mycoplasms has been involved in the generation of atheroma plaques and arthritis. Moreover, because of the massive use (in medicine and farming) of antibiotics, the bacterial world is changing, giving rise to more resistant forms, inaccessible to antibiotics and antibody response, capable of staying latent inside cells for a long time.

Therefore a strong research effort should be undertaken in this field by seeking refined techniques of diagnosis and new ways of treatment. Identification of the infectious components of chronic diseases will also lead to a new approach of their prevention.

In conclusion, prevention of age-related diseases is the only way to avoid a disastrous end of life at the individual level and a likely collapse of social security systems at the societal level. It will imply profound changes in the mentality of individuals, medical doctors and policy-makers.

Each of us should consider optimization of his biological capital and accept regular check-up in specialized centers. Medical doctors should receive specific training on the prescription of anti-oxidants, and rather treat the patient than the disease, in an integrative way. Health authorities should promote the implementation of Centers of Preventive Medicine and take financial measures (bonus, tax reduction) to incite citizens to attend regular check-up. In addition more money should be spent in medical research for prevention than for treatment of diseases. Indeed the pharmaceutical industry should reorientate its research and development strategy towards preventive treatments and diagnosis.

Finally this approach will also benefit to the prevention of epidemics caused by new infectious agents: generally such epidemics first hit people with a depressed immune system, particularly the elderly ones. Restoring their immune system will also greatly contribute, in a inexpensive manner, to reduce mortality and morbidity.

Conflict of interests: Luc Montagnier is the uncompensated scientific advisor of several companies involved in the field.

T3 et T4

Dr Thierry Hertoghe — 2005-11-30T20:27:47Z

The International Hormone Society's Consensus Group of experts on Hormone Therapies Consensus nr 1 on “Thyroid Hormone Therapy of Hypothyroidism”of the 29-9-2005

After having reviewed the scientific literature and exchanged experiences between physicians from all over the world and who are competent in hormone therapies, we, members of the Consensus Group of Experts of the International Hormone Society, think the time is ripe to reconsider current concepts on thyroid treatment of hypothyroidism.

The view that hypothyroidism is best treated by thyroxin alone is not based on solid scientific evidence. The studies with comparison of the efficacy of thyroxine alone versus that of associations of thyroxine and triiodothyronine medications have in general not shown superiority of thyroxine alone above the associations of thyroxine with a smaller dose of triiodothyronine. On the contrary, a few studies have shown significantly greater efficacy of combined thyroxine-triiodothyronine medications compared to the use of thyroxine alone in humans on such divergent parameters as serum cholesterol, mental and physical symptoms, and in animals on goitre formation and intracellular triiodothyronine(T3)-euthyroidism, just to name some of the greater benefits. The fact that T3 is the major intracellular thyroid hormone, that it is the low serum level of T3 that forms, more often than serum T4 (thyroxin) or TSH, the critical parameter in mortality studies, especially cardiovascular, and that the absorption of T3 is much more efficient and stable than that of T4, give credit to the view that associations of thyroxin with triiodothyronine may better fit the hypothyroid patient.

The evidence is sufficient to guarantee the physician a freedom of choice in thyroid medication: either thyroxin alone, either thyroxin and triiodothyronine.

As hypothyroidism has serious adverse consequences on the quality of life and health of patients, we recommend physicians at the light of the solid evidence here collected, to first try with hypothyroid patients a combined thyroxin and triiodothyronine preparation.

As the association treatment contains the immediately active triiodothyronine, we recommend physicians to follow some safety guidelines, next to the classical ones such as avoiding overdoses, when they administer thyroxin and triiodothyronine medications. Following these measures increases the safety and tolerance of the treatment. The first guideline is to start the treatment at very low doses and then to slowly and gradually increase the dose until clinical euthyroidism is reached. The second guideline is to tell their patient to avoid all caffeinated and similar stimulating drinks that may increase the orthosympathic activity. The third guideline is to regularly follow-up the patients with a good clinical interview and examination and laboratory tests every two to twelve months depending on the patient's needs. The forth guideline is to carefully screen for adrenal deficiency in hypothyroid patients as patients with low or borderline low cortisol levels may poorly tolerate any type of thyroid medication, and in particular thyroxin-triiodothyronine combinations. The intolerance may come from overactivity of the orthosympathic nervous system that often accompanies states of low cortisol, and an excessive and rapid conversion of thyroxin to triiodothyronine that puts these patients easily into a state of excess T3 and thus hyperthyroidism, and further increases the orthosympathic activity. In patients with cortisol deficiency, we recommend the physician to treat the low cortisol state prior or concomitantly to the thyroid treatment. If not, thyroxin alone may be the better treatment of hypothyroidism in the presence of an untreated cortisol deficiency. In most other states, thyroxin and triiodothyronine remains the first, but not exclusive, choice for treatment of hypothyroidism for the International Hormone Society's consensus group.

Concerning the debate about which association treatment works best: synthetic T3-T4 or dessicated thyroid, the consensus group states the following. Reports of patients feeling better on dessicated thyroid may have scientific evidence as these preparations contain next to T3 and T4 also a number of other substances that may have some thyroid activity as diiodo-and monoiodo-thyronines. In addition, the binding of much of the thyroid homones to the bigger thyroglobulin molecule permits a slower intestinal absorption and, later, once arrived in the bloodstream, a slower release of thyroid hormones in the blood, thereby insuring a more persistent action and a better tolerance by spreading the action over a longer time. Thus, dessicated thyroid may work better. The view that the potency of thyroid preparations of animal origin may have more fluctuations has arguments. For this reason, preference is given to preparations that are officially registered and well-controlled. It must be said that the frequent FDA-recalls of poorly reliable, less potent than announced thyroxin preparations of various pharmaceutical firms in the USA, makes thyroxin not a better alternative. In the light of the Mad Cow's disease, the International Hormone Society does not recommend the use of dessicated thyroid of beef origin. For these reasons, the position adopted by the consensus group members of The In,ternational hormone society is that both type of T3 -T4 preparations have their pros and cons, and the freedom of choice between these two should be left over to the physician.

IHS GH

Dr Thierry Hertoghe — 2005-11-30T20:23:53Z

The International Hormone Society's Consensus Group of experts on Hormone Therapies Consensus nr 5 on “Growth Hormone Therapy of Milder Forms of Growth hormone Deficiency in Adults” of the 29-9-2005

After having reviewed the scientific literature and exchanged experiences between physicians from all over the world and who are competent in hormone therapies, we, members of the Consensus Group of Experts of the International Hormone Society, think the time is ripe to consider treating growth hormone deficiency in adults, not only severe, but also milder forms.

We acknowledge and approve the consensus that has been reached in many countries for growth hormone treatment of adults suffering from severe growth hormone deficiency after important head injury, surgery or radiation of tumours in the pituitary region. Generally, in such conditions there is a history of removal or severe inactivation of the pituitary gland, the endocrine gland that secretes growth hormone.

We think that the amount of supporting data on growth hormone's beneficial effect is now sufficient to extend the recommendation of growth hormone treatment to patients with milder forms of growth hormone deficiency such as those that progressively appear in adults of increasing age, because of the progressive age-related decline of the pituitary gland.

The evidence is that growth hormone is not only essential for the growth of children, but also essential for mental and physical (in particular bone, muscular and cardiovascular) health of adults, including elderly persons. Growth hormone deficiency is often accompanied by fatigue, anxiety and depression, summarized in a low quality of life, often severe in persons whose growth hormone deficiency started in late adulthood, as confirmed in many studies. On the other hand, growth hormone treatment has been reported to considerably improve the quality of life, the mood and the sleep. Not treating the milder forms of growth hormone deficiency in elderly persons may much more seriously than thought before, adversely affect human health. The increased atherosclerosis and mortality, especially cardiovascular, that are found in individuals who suffer from severe growth hormone deficiency, and that partially or totally reverse with growth hormone correction, make it likely that such problems also occur in some degree in patients with more moderate deficiencies, and may likewise be improved by growth hormone injections.

We recommend the physicians to do a regular check-up of any patient treated with growth hormone. This includes doing a good clinical interview and examination, and laboratory tests every two to twelve months depending on the patient's needs. A regular cancer screening, including breast and prostate examination, every year or six months eventually completed by ultrasound examination, and whenever necessary mammography, is essential to the Consensus Group of Experts of the International Hormone Society.

Concerning an eventual increase in risk of certain cancers with growth hormone, the data are conflicting. In some investigations protective effects against cancer are reported, while in other studies increases of risks for patients with high serum IGF-1 and low serum IGF-BP-3 were found. The most serious study done on patients treated with growth hormone compared to a group of untreated growth hormone-deficient adults showed an approximate 50 % decrease in cancer incidence and cancer mortality. Actually, there is no convincing evidence to believe there is an increase in cancer risk in most individuals treated with growth hormone. Nonetheless, we recommend physicians to administer only physiological doses that correct the deficiency, avoiding thereby carefully to overtreat. By following this principle, the physician further increases the safety of the treatment.

After thoroughly reviewing the report of two studies where critically-ill patients encountered a doubling of the mortality rate with growth hormone compared to a similar group of critically ill patients without growth hormone, we can say the following. This “negative” report forms an exception. The critically ill patients received clearly supraphysiological doses: 10 to 50 times higher than physiological. At physiological doses -20 to -40 % reductions of cortisol serum levels and urinary 17-hydroxy-steroids, the cortisol metabolites, have been observed. At supraphysiological doses the cortisol-reducing effect of growth hormone that in normal people is a way to prevent any excess in cortisol, more than probably weakens the critically-ill patient who crucially needs high doses of cortisol for his survival. The increased mortality of the treated patients was due to infections and polyorgan failure, conditions typical of severe adrenal failure. The results of the study are probably due to overtreatment and possibly also to neglectment of glucocorticoid supplementation, not to growth hormone per se. The use of physiological doses of growth hormone and more than probably glucocorticoid supplementation would have been much safer and might have reduced mortality rather than increase it.

In conclusion, no convincing data against the use of growth hormone in adults suffering from low growth hormone or IGF-1 levels have been found. On the contrary, adverse effects of persisting low growth hormone levels have been abundantly reported, as has their improvement or disappearance with growth hormone treatment.

We therefore recommend to treat with growth hormone cancer-free adults with low growth hormone and IGF-1 levels. Growth hormone treatment should be restricted to physiological doses and be accompanied by careful and regular check-ups.