Дата публикации: 10 ноября 2021
Автор(ы): Lev PANIN
Публикатор: Научная библиотека Порталус
Источник: (c) Science in Russia, №6, 2013, C.20-26
Номер публикации: №1636551300

Lev PANIN, (c)

by Academician Lev PANIN, RAMS, Director of the Research Institute of Biochemistry, RAMS Siberian Branch (Novosibirsk)


The European and Asian North of Russia is a territory of active economic development. However, the natural and climatic conditions of polar latitudes are severe and often even extreme for humans. Therefore, a new trend of public health has to be developed: arctic medicine--with a special emphasis on specific features of the course of many diseases in the North--inflammation, immune diseases, cardiovascular diseases, mental disorders, etc. The preventive system acquires special significance here.


The Northern regions occupy great areas in Canada, USA (Alaska), Scandinavian countries, including Denmark with its Greenland. However, the largest Northern territories are in Russia: only in Siberia their area is 3.8 mln km2. Here, in Yakutia, the cold pole of the Northern hemisphere is situated in Oimyakon, Verkhoyansk. In the permafrost regions, where seasonal fluctuations of temperature can exceed 100 °C, where live small populations of Siberia and the North, enormous economic activity is in progress, which is connected with the development of natural mineral resources-oil, gas, coal, gold, diamonds, polymetallic ores, etc. The Arctic Ocean shelves are particularly interesting as regards gas and oil production. The economic inter-

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ests have been determining and will determine in future the migration of the population from regions with more mild climatic conditions to the North.


How can we promote adaptation of man to the extreme ecological conditions of the Polar regions, maintaining their health status and work capacity at a high level? Attempts to solve this problem has led to the emergence of a new trend--arctic medicine. The Siberian Branch of the Academy of Medical Sciences of the USSR was established in 1970 in Novosibirsk in order to organize research in this sphere, with one of its constituent parts--Institute of Clinical and Experimental Medicine. It was headed by a well-known clinicist Acad. Vlail Kaznacheyev (member of the USSR Acad, of Med. Sc. from 1971). Today it is a big scientific center for studies of basic and applied problems of vital support of man under severe climatic conditions of Siberia, Extreme North, and Arctic Regions.


The contribution of the Novosibirsk Research Center to the development of arctic medicine is really important. Many-year intense expeditions to the territories of Asiatic North, Arctic and Antarctic regions made scientists form absolutely new concepts on human adaptation. It has been found that all kinds of metabolism--proteins, fats, carbohydrates, vitamins, macroand micro-elements--are modified under extreme conditions of high latitudes. The author of this paper has demonstrated the formation of a polar metabolic type. The organism is transferring to a new homeostasis level, characterized by new ecologically-conditioned


* Homeostasis is a dynamic constancy of the internal media composition and characteristics, and stability of the main physiological functions of man, animals, and plants.--Ed.


standards of the health state, new criteria for evaluation of the functional activities of organs and systems. For example, transfer from carbohydrates to lipids is essential for energy metabolism. As a result, the contribution of carbohydrates to energy metabolism reduces, while that of lipids increases. Blood concentrations of lipid transport forms increases--lipoproteins (LP) of very low (VLDLP) and low density (LDLP)--the atherogenic forms ("harmful" lipid fractions settling on vascular walls). Nevertheless, in the North this does not lead to the development of atherosclerosis or coronary heart disease. High activity of lipid metabolism enzymes (lipoprotein lipase and triglyceride lipase), associated with the inner vascular surface, leads to a significant increase in the concentrations of high density lipoproteins (HDLP) with antiatherogenic properties. Besides, the balance of atherogenic/antiatherogenic LP forms in the blood is restored. Moreover, it is even shifted towards the latter. The relative content of HDLP in the blood can reach 60 percent, and this is a good sign. To be sure, there are cardiovascular disease risk factors in the North, and they are the same as anywhere else. It is stress (state of anxiety), irregular diet, hypodynamia, harmful habits (tobacco smoking, alcoholism). In the North they are more active.


VLDLP and LDLP are risk factors for diabetes. We were the first to show that apolipoprotein B (apo B) in the structure of atherogenic LP forms is characterized by a counter-insular effect (suppressing insulin effect) and promotes development of diabetes-2. Besides diabetes is often diagnosed in a patient if sugar is found in his/her urine. However, inverse absorption of sugar and other low-molecular compounds (for example, vi-

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Structure of biological membranes (Singer, Nicolcon, 1972). * Areas of peroxidal oxidation of lipids.


tamins) from primary urine (forming in the renal glomeruli and including all plasma components, except proteins) is low in residents of the North. The presence of sugar in the urine is paralleled by its normal or low concentrations in the blood, while blood insulin content is also reducing. Such "diabetes" is not a pathology. It is ecologically-conditioned and functional. But one should remember that diabetes-2 can also easily develop in the North. If an individual is exposed to chronic stresses, uses carbohydrates in excess, and does not move much (hypodynamia)--we have a complete set of risk factors for this disease. A physician working in the Extreme North should know these facts. What is physiological (functional) essence of this diabetes?


No doubt, an individual perceives the extreme conditions of the North and territories close to the Polar Circle as a stress. But no individual can permanently live in a state of stress. It is a well-known fact that stress is associated with an increase of blood concentrations of steroid hormones. However, their concentrations in man living in the North are just slightly higher than in residents of other regions with a milder climate. It has turned out that the organism uses one more mechanism of reaction to stress: reduces blood concentration of insulin--a counter-hormone for steroid hormones (glucocorticoids). We call this kind of diabetes "stress diabetes"; a similar disease was observed in the 1880s by Claude Bernard, a French physiologist; he detected sugar in the urine of rabbits eating carrots. He called it "hungry diabetes". Later on we have reproduced these results in our works and demonstrated that sugar appears in the urine under conditions of fasting, while its concentrations remain normal in the blood.


We disclosed the mechanism of this phenomenon later on. It turned out that it is associated with the anti-insulin effect of apolipoprotein B, a component of LDLP and VLDLP. This kind of "diabetes" is a basis of energy metabolism switch-over from a carbohydrate type to a lipid type under extreme conditions of the Extreme North, where the processes of glucose formation from proteins and partially from lipids become the main sources of carbohydrates necessary for the brain and other tissues. These processes run actively in the liver. Glucose excess in the diet disturbs this mechanism.


Naturally, these changes in all kinds of metabolism necessitate special diets. In the North the need in carbohydrates reduces, while the need in proteins and lipids increases. A drop of carbohydrate metabolism reduces the requirements in some water-soluble vitamins, such as B, and B2, while simultaneous intensification of lipid metabolism requires lipid-soluble vitamins A, D, and E, working as antioxidants for unsaturated fatty acids. Their role is particularly noticeable in high latitudes as cell membranes have to be protected from peroxidation of the above acids (phospholipid components). The increased ultraviolet radiation, ionizing effects of solar wind particles promote active formation of lipid peroxides and of protein-lipid sutures, which leads to rapid aging of cells. This is particularly evident in case of erythrocytes, their life span reducing in high latitudes.

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This phenomenon promotes the development of "polar dyspnea", observed in newcomers, particularly under conditions of physical loads.


We observed this while examining members of the team of skiers participating in the transarctic ski march, headed by Dmitry Shparo in 1988. They pointed out that "the most unpleasant combination was probably the 40° frost and head wind. The rhythm of the march was intense: 50 min of walking and 10 min of rest, 8-9 hours daily. During stops we were literally falling from fatigue."


The cell membranes need active antioxidant protection in high latitudes. For example, the formation of unsaturated fatty acid hydroperoxides and protein-lipid sutures increase microviscosity of erythrocyte membranes and impede erythrocyte passage in blood capillaries. As we know, their diameters are comparable with the erythrocyte diameter. This can lead to development of diffuse tissue hypoxia and rapid fatigue, particularly in case of active physical work.


This problem is rather effectively solved in the indigenous population of the Extreme North due to the traditional protein and lipid diet. In the tundra aborigines it has not changed in fact up to the present time: their main food is venison and fish from the local water bodies. The diet of aborigines living by the sea includes the meat of sea animals (seal, walrus), sea fishes, and just a few imported foodstuffs (bread, salt, sugar). Meat and fish for them are the main source of proteins with the full-value amino acid composition, lipids containing


Changes of tocopherol content and products of peroxidal oxidation of lipids in erythrocytes in dynamics of ski-crossing (M±m)


Content of tocopherol and products of POL


North Pole


Tocopherol, mg/100ml

0.48+0.01 (n=13)

0.22+0.03* (n=7)

0.15±0.06* (n=13)

Products of POL, rel. units

1.07±0.36 (n=13)

2.25+0.21* (n=2)

1.04+0.11 (n=12)


Note. Differences are trustworthy (p<0.05): * as compared with Dickson


unsaturated fatty acids and lipid-soluble antioxidants (vitamins A, E, D). In addition, these foodstuffs contain the essential minerals. By contrast, the diets of newcomers are different, that is why we recommend natural as well as synthetic antioxidants to them.


One more problem for newcomers in the Extreme North: low mineralization of water in the local rivers. This is explained by its dilution due to active snow melting in spring and summer. The problem of macro- and micro-element deficiency emerges during this period. As minerals play an important role in assimilation of vitamins, drinking of low-mineralization water leads to the development of secondary hypovitaminoses. We have shown that addition of vitamin-and-mineral compositions to the diet is an effective method of

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their control (by the way, a similar problem was solved for space medicine). In the North we used not only the vitamin-and-mineral compositions, but also natural additionally vitaminized foodstuffs (juices, milk, infusions of wild plants). They proved to be much more effective in hypovitaminoses control than the standard polyvitamins.


Dealing with the problem of human adaptation in the North, we studied one more factor involved in metabolic changes. It is known that macrophages are key cells of the immune system. However, they are also essential for blood lipoprotein (HDLP, LDLP, and VLDLP) metabolism. Lipoprotein metabolism is much higher in residents of the North, and this is “hard work” for macrophages, particularly in the liver. Transition of these cells to metabolic functions reduces their role in the formation of immune response. For example, in the North this leads to the "breakthrough" of the enteric microflora antigens into human lymphoid system with subsequent stimulation of the immune response. The data obtained by Dmitry Mayansky, Dr. Sc. (Med.), Institute of Human Pathology and Ecology, Siberian Branch of the Russian Academy of Medical Sciences, indicate that the residents of the North have high titers of antibod-


North Asiatic type of diet


Product set




Aldan district






























Chemical composition of Nganasans' ration

Proteins, g

Fats, g

Carbohydrates, g

Calorie content, Kcal

In all

Incl. animal

In all

Incl. animal







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ies to the common allergen-reactive fraction of enterobacteria.* This has been most evident for the first 10 years of living in the Arctic latitudes. Inhibition of the "macrophage filter" work in relation to the bacterial and viral infection determines man's higher liability to infections in the North. A similar situation is observed for the course of inflammatory processes.


We have demonstrated for the first time that a macrophage is responsible for cell regeneration processes in a pathological focus of any etiology. The gene expression and protein synthesis in the cells in a focus of inflammation are stimulated by a cooperative mechanism of activities of cell degradation products, steroid hormones, and HDLP. It is also realized in macrophages and leads to the formation of a bioactive complex: reduced forms of steroid hormones (tetrahydrocompounds) and protein (apolipoprotein A-I). This complex triggers regeneration processes. Inhibition of the phagocytic activity of macrophages suppresses the activity of this mechanism, and the inflammatory pathology transforms into a chronic one--physicians in the North constantly observe this phenomenon.


Let's emphasize that inflammation and immunity are closely related. Ilya Mechnikov, a Russian biologist, No-


* Enterobacteria is a family including such well-known pathogens as salmonella, Pasteurella pestis, etc. On the other hand, many representatives of the family are components of normal enteric microbiota.--Ed.


bel Prize winner of 1908, wrote, "Inflammation is the most important manifestation of immunity". The same idea is developed by Ippolit Davydovsky, a pathologist, "We can speak about immunity's closeness to inflammation in principle, no matter whether we mean that immunity is essential for inflammation or, vice versa, inflammation is significant for immunity" (I. Davydovsky, Human Pathology. Moscow, Meditsina Publishers, 1969). One can easily see that it is really so in the North.


The Arctic regoins means cold. Man adapted to it "prefers" oxidation of fatty acids (as we have shown above). Part of oxidation energy is spent to warm oneself, part for chemical or physical work. The heat production in the North is higher, as a result of which the work efficiency coefficient is lower. Hence, the calorie content of the daily diet of residents of the North should be 10 percent higher for normal work than in regions with the temperate climate.


It is noteworthy that an individual adapted to cold does his/her best to minimize thermal loss. The weighted mean of temperature of the skin of this individual is reducing. Even the body temperature can reduce, though negligibly. We say that the thermoregulation system acquires a different homeostasis level. However, there are exclusions in the North. Individuals who prefer warm clothes lose the capacity to adapt to cold. Frost bites and even freezing (often in a state of alcoholic intoxication) are rather frequent for them.

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There have been revealed specific features of the use of pharmacological preparations for treatment of different diseases in Polar regions. They include hyperoxidation in the xenobiotic (foreign compounds) metabolism and their active clearance (secretion from the body). This problem is very important and should by no means be neglected when developing the Arctic territories.


One more important factor. Living in the middle and low latitudes, people get used to regular and inevitable alternation of day and night. This forms the circadian (about 24 h) rhythms in the organism. The activities of all functional systems of the organism become rhythmic. In the North the "light periodicity" is quite different. The polar day is replaced by polar night, between which the day/night alternation is more habitual for us, determining the common 24-h day and night hours. The intrasystemic and numerous intersystemic relations in the organism get disturbed. There develop desynchronoses as a basis of formation of chronopathology. Clinically it leads to a lower mental and physical work capacity, sleep disorders, emotional instability, unpredictable behavior, etc.


Signs of sensory deprivation (insufficiency of external stimuli) emerge during the polar night. An individual develops depressiveness, sometimes with suicidal attempts. By contrast, during the polar day dominate increased excitability of the central nervous system, irritability, sleep disorders, different vegetative disorders (primarily cardiogenic), etc. All these symptoms require proper psychotropic therapy and adequate strategy of a physician--neurologist and psychiatrist.


We have shown that the mental stress syndrome plays an important role in the development of psychosomatic pathology in the North. Its main sign is a feeling of anxiety. It is an emotional shade of a state, characterized by expectation of unpredictable threat and by forestalling mobilization of energy resources and reserve potentialities of the organism. Distress is a functionally closer notion to it (the term was suggested by Hans Selye, a Canadian endocrinologist, in 1960). Clinically anxiety is accompanied by an increase of the inner strain, irritability, and, as the symptoms accumulate, can transform into neurosis or depression. Such states are adequately corrected by benzodiazepine tranquilizers (seduxene, elenium), inhibiting the activities of the central mechanisms of regulation--they are called monoaminoergic systems of the brain. Hence, anxiety forms under conditions of their hyperactivity. The emergence of psychosomatic disease is determined by the individual characteristics of higher nervous activity. Introverts, trying to find a cause of conflicts in themselves, develop coronary heart disease, while their antipodes--extroverts--develop essential hypertension. Other manifestations of psychosomatic pathology are also possible, for example, nervous diseases, gastroduodenal ulcer.


We have found greater alcohol dependence in residents of the Extreme North. Its formation is about 5 years more rapid here than in the middle latitudes. The northern residents have a lesser rate of oxygen-free (anaerobic) carbohydrate oxidation (glycolysis) in some cells, metabolic branching of which is formation of endogenous (one's own) ethanol. Reduction of the ethanol production, involved in the "construction" of positive mood hormones, leads to the necessity to stimulate its blood level by alcoholic drinks. Gradually this forms metabolic dependence on such drinks. This can be controlled. We have experimentally developed a recipe of an alcohol control drug PL-alko and got permission to use it for correction of the above metabolic disorders in humans. The drug proved to be rather effective.


Unfortunately, the northern pharmacology and polar medicine have not yet become available for a practicing physician. They need further development. However, the base for this development is created by research carried out at the Institute (now Center) of Clinical and Experimental Medicine, Research Institute of Biochemistry, Research Institute of Physiology (RAMS SB), and other scientific institutions of the country.


Concluding, we should like to emphasize that the problem of human health in the North is closely connected with the "health" of the North proper, its highly vulnerable nature. Barbaric handling of nature has already irreparably harmed it. What is in store for us, when the development of the Arctic Ocean shelves will start? Their ecosystems are even more vulnerable than dry land zones. We should start to think about it now.


Illustrations supplied by the author

Опубликовано на Порталусе 10 ноября 2021 года

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