Selected biomarkers of age-related diseases in older subjects with different nutrition.

BACKGROUND: The nutritionists introduce on the base of epidemiological and clinical studies that appropriately planned vegetarian diets are healthful, and may provide health benefits in the prevention and treatment of certain diseases. Aging belongs to the main risks of cardiovascular disease. METHODS: Markers of age-related diseases (cardiovascular, metabolic syndrome, diabetes) were assessed in two nutritional groups of older apparently healthy non-obese non-smoking women aged 60-70 years, 45 vegetarians (lacto-ovo-vegetarians and semi-vegetarians) and 38 non-vegetarians (control group on a traditional mixed diet, general population). RESULTS: Vegetarian values of total cholesterol, LDL-cholesterol, triacylglycerols, C-reactive protein, glucose, insulin and insulin resistance are significantly reduced. Non-vegetarian average values of total cholesterol, LDL-cholesterol and C-reactive protein are risk. Vegetarians have a better antioxidative status (significantly increased vitamin C, lipid-standardized vitamine E and beta-carotene plasma concentrations). CONCLUSION: Favourable values of cardiovascular risk markers in older vegetarian women document a beneficial effect of vegetarian nutrition in prevention of this disease as well as the vegetarian diet can be an additional factor in therapy. Vegetarians suffer from mild hyperhomocysteinemia; it is due to the lower vitamin B12 concentration. Vitamin B12 supplements are inevitable for the hyperhomocysteinemia prevention (Tab. 2, Ref. 26).

Effects of diet and age on oxidative damage products in healthy subjects.

Damage of molecules as a consequence of oxidative stress has been implicated in the pathogenesis of chronic diseases related to aging. Diet is a key environmental factor affecting the incidence of many chronic diseases. Antioxidant substances in diet enhance the DNA, lipid and protein protection by increasing the scavenging of free radicals. Products of oxidative damage of DNA (DNA strand breaks with oxidized purines or oxidized pyrimidines), lipids (conjugated dienes of fatty acids) and proteins (carbonyls) in relation to nutrition (vegetarian diet vs. non-vegetarian, traditional mixed diet) were measured in young women aged 20-30 years (46 vegetarians, 48 non-vegetarians) vs. older women aged 60-70 years (33 vegetarians, 34 non-vegetarians). In young subjects, no differences in values of oxidative damage as well as plasma values of antioxidative vitamins (C,beta-carotene) were observed between vegetarian and non-vegetarian groups. In older vegetarian group significantly reduced values of DNA breaks with oxidized purines, DNA breaks with oxidized pyrimidines and lipid peroxidation and on the other hand, significantly increased plasma values of vitamin C and beta-carotene were found compared to the respective non-vegetarian group. Significant age dependences of measured parameters (increase in all oxidative damage products and decrease in plasma vitamin concentrations in older women) were noted only in non-vegetarians. Vegetarian values of older women vs. young women were similar or non-significantly changed. The results suggest that increase of oxidative damage in aging may be prevented by vegetarian nutrition.

Vitamin C protective plasma value.

The relationship of plasma concentration and intake of vitamin C was measured in a randomly selected group of 368 apparently healthy adult subjects of two nutritional regimens: traditional mixed diet (general population, n=187) and vegetarians (n=181). The condition of protective plasma concentration over 50 micromol/l (50.3-89.4 micromol/l), the value of which reduces the risk of free radical disease, was found in 87 subjects from the general population group, in whom the average vitamin C intake was 124.2 mg per day in range of 92-181. The recommended dietary allowance for this group in amount of 77 mg of vitamin C daily was calculated from current Slovak recommendations being in amount of 80 mg per day for men and 75 mg for women. Previous epidemiological studies as well as the presented results show that approximately a half of Slovak general population have vitamin C deficient (below 23 micromol/l) or suboptimal (23-50 micromol/l) plasma concentrations with insufficient antioxidative protection. Significantly higher plasma vitamin C concentrations in comparison to non-vegetarians were observed in the vegetarian group. Protective concentrations were noted in 88% of vegetarians vs 46% of non-vegetarians. The significantly reduced values of products of oxidative damage of DNA (DNA breaks with oxidised purines and oxidised pyrimidines), lipids (conjugated dienes of fatty acids, malondialdehyde) and proteins (carbonyls) were found in subjects with plasma vitamin C concentrations being over 50 micromol/l vs. below 50 micromol/l. The data emphasize the role of vitamin C in free radical disease prevention under the condition of protective, antioxidative concentrations. The results of general population group document the need to revise the recommended dietary allowance for vitamin C as well as to change the nutritional habits including regular consumption of fruit and vegetables several times daily (Tab. 3, Ref. 28).

Nutritional determinants of plasma homocysteine.

The total Hcy, methionine, vitamin B12, folic acid and vitamin B6 blood concentrations were measured in apparently healthy adult subjects aged 20-30 years with three types of nutrition - 52 normal weight subjects of general population on traditional mixed diet (non-vegetarians), 52 normal weight vegetarians and 24 overweight and obese non-vegetarians. In the groups with lower methionine intake (vegetarians, normal weight non-vegetarians; methionine intake 0.45-2.12 g/day), Hcy values are dependent on vitamin B12 and folic acid. Vegetarian Hcy concentration is significantly increased and hyperhomocysteinemia was found in 35% of vegetarians vs 10% of non-vegetarians. Elevated Hcy values in vegetarians are the consequence of vitamin B12 deficiency - 31% of vegetarians with deficient serum values vs 2% of non-vegetarians (vitamin is not contained in plant food). Non-vegetarians are more deficient in folic acid (8% vs 0% in vegetarians) due to of lower consumption of food rich in folic acid (vegetables, whole grain products, pulses, seeds). The results suggest that in healthy population, a correct nutritional regime with an optimal intake of nutritional Hcy determinants is crucial for the maintenance of Hcy concentration in normal range and for the prevention of hyperhomocysteinemia (Tab. 2, Fig. 2, Ref. 27). Full Text (Free, PDF) www.bmj.sk.

Products of DNA, protein and lipid oxidative damage in relation to vitamin C plasma concentration.

Oxidative stress plays an important role in the pathogenesis of numerous chronic age-related free radical-induced diseases. Improved antioxidant status minimizes oxidative damage to DNA, proteins, lipids and other biomolecules. Diet-derived antioxidants such as vitamin C, vitamin E, carotenoids and related plant pigments are important in antioxidative defense and maintaining health. The results of long-term epidemiological and clinical studies suggest that protective vitamin C plasma concentration for minimum risk of free radical disease is higher than 50 micromol/l. Products of oxidative damage to DNA (DNA strand breaks with oxidized purines and pyrimidines), proteins (carbonyls) and lipids (conjugated dienes of fatty acids, malondialdehyde) were estimated in a group of apparently healthy adult non-smoking population in dependence on different vitamin C plasma concentrations. Under conditions of protective plasma vitamin C concentrations (>50 micromol/l) significantly lower values of DNA, protein and lipid oxidative damage were found in comparison with the vitamin C-deficient group (<50 micromol/l). The inhibitory effect of higher fruit and vegetable consumption (leading to higher vitamin C intake and higher vitamin C plasma concentrations) on oxidation of DNA, proteins and lipids is also expressed by an inverse significant correlation between plasma vitamin C and products of oxidative damage. The results suggest an important role of higher and frequent consumption of protective food (fruit, vegetables, vegetable oils, nuts, seeds and cereal grains) in prevention of free radical disease.

Lipid peroxidation in relation to vitamin C and vitamin E levels.

Oxidative stress plays an important contributory role in the pathogenesis of age-related chronic diseases. Increased lipid peroxidation process is caused by an enhanced free radical formation together with a higher supply of substrates and by an insufficient defense by antioxidants as well. Levels of malondialdehyde to content of lipid peroxidation substrates (polyunsaturated fatty acids), promoters (homocysteine--hydroxyl radical producer) and inhibitors (essential vitamins C and E) were estimated in a group (n=92) of subjective healthy adults randomly selected from general population. The relationship of malondialdehyde levels to values of peroxidisability index of fatty acids as well as to levels of homocysteine is significantly positive linear A significant inverse linear correlation between malondialdehyde levels and natural antioxidant levels (vitamin C, vitamin E) was recorded. Lipid peroxidation products (conjugated dienes of fatty acids--initial, malondialdehyde--secondary) are significantly increased in groups of subjects with deficient levels of vitamin C (below the limit from antioxidative point of view), vitamin E and both vitamins, if compared to group with normal vitamin levels (over limit in accordance with antioxidative criterion). The results document that the deficiency in two key antioxidants for lipid peroxidation inhibition means the insufficient defense against free radicals and the increased lipid peroxidation.

Lipid peroxidation and nutrition.

Levels of conjugated dienes of fatty acids (first peroxidation product) in relation to their substrates and promotors (triacylglycerols, homocysteine, iron) as well as to their inhibitors (essential antioxidative vitamins) were assessed in a vegetarian group (n=24) and compared with subjects on a mixed diet (traditional nutrition, n=24). Positive significant linear correlation between conjugated dienes and triacylglycerols, homocysteine, iron as well as inverse relationship between conjugated dienes and vitamin E, vitamin C, beta-carotene were observed in pooled groups. Lipid peroxidation risk in vegetarians seems to be caused predominantly by hyperhomocysteinemia, whereas in a mixed diet group this was due to a higher supply of substrates or risk iron values. The incidence of only 8 % of risk conjugated diene values in vegetarians in contrast to 42 % in the group with traditional diet indicates that vegetarians have a better antioxidative status as a consequence of regular consumption of protective food.

Antioxidant vitamins levels--nutrition and smoking.

The plasma levels of antioxidant vitamins express the risk rate of free radical disease. Limit values (risk threshold) were determined in long-term epidemiological and clinical studies. Over-threshold (optimal) values mean an effective protection and a reduced risk of the disease. Values below threshold (deficient) from antioxidant point of view increase this risk. Optimal levels of each antioxidant at different age are required for the maintenance of optimal health. Vitamin C and beta-carotene are derived from fruits and vegetables. The decrease of antioxidant vitamins in smokers caused by free radical presence in tobacco smoke is known. The levels of vitamins C, E and beta-carotene were estimated in two ethnic groups of young adult population of Western Slovakia (n = 122--Gipsy minority; n = 137--majority population). Vitamins levels are correlated to nutrition, smoking and education. Vitamin E levels are similar in both groups; frequency of values with optimal antioxidant effect is equal (21%). In Gipsy group are significantly reduced the vitamin C and beta-carotene levels with only 28% over-threshold values of vitamin C and 7% over-threshold values of beta-carotene vs 46% and 25% in the majority group. The reduced levels of antioxidant vitamins in Gipsy minority group are a consequence of inadequate nutrition (lower and infrequent consumption of fruit and vegetables, low knowledge about optimal nutrition affected by low education--85% of Gipsy subjects have elementary and apprentice education vs 27% of majority subjects) and smoking (smokers--55% of Gipsy persons vs 25% in majority group subjects; 42 and 50% reduced vitamin levels in smokers). (Tab. 1, Fig. 1, Ref. 17.).

[Spheroid formation in explants of human breast tumor and fibroadenomatous tissues and lymphoid infiltration of explants during cultivation in diffusion chambers]. / Obrazovanie sferoidov v éksplantatakh opukholevoi i fibroadenomatoznoi tkanei molochnoi zhelezy cheloveka i limfoidnaia infil'tratsiia éksplantatov pri ikh kul'tivirovanii v diffuzionnykh kamerakh.

An extensive formation of epithelioid cell spheroids was shown during tumour tissue growth on millipore filters. In addition, the appearance of such multicellular structures as an early sign of malignant transformation was demonstrated in some fibroadenomatous tissue cultures. The increased fibroadenomatous tissue proliferative activity was accompanied by the rising level of lymphoid cell infiltration.