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Biomedical subjects

M Mutanen

Publications and source records attributed to M Mutanen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Similar effects of diets high in oleic or linoleic acids on coagulation and fibrinolytic factors in healthy humans.

BACKGROUND AND AIM: Monounsaturated fatty acids (MUFA) have been shown to be beneficial. Their haemostatic effects, however, are poorly known. We compared the effects of oleic acid (OA) and linoleic acid (LA) on variables related with coagulation and fibrinolysis in healthy subjects. METHODS AND RESULTS: Thirty-eight healthy volunteers (20 women, 18 men; mean age 27) consumed a saturated fat baseline diet for four weeks and were then switched to either a high LA diet (11.5 en%) or a high OA diet (18.0 en%) for another four weeks when nearly all food was provided for the whole day. A control group of 13 subjects consumed their habitual diet throughout the study. No differences between the OA and LA diets were found in the plasma levels of fibrinogen, plasminogen activator inhibitor, antithrombin III, von Willebrand factor antigen or D-dimers. Factor FVII coagulant activity was significantly lower after the OA diet. CONCLUSIONS: The results indicate largely similar effects for OA and LA on factors related with coagulation and fibrinolysis in humans. The effects of dietary fatty acid composition on FVII coagulant activity should be further studied.

Adult↗
PubMed1998

A high linoleic acid diet increases oxidative stress in vivo and affects nitric oxide metabolism in humans.

Evidence from in vitro studies shows that increased intake of polyunsaturated fatty acids leads to increased oxidative stress, which may be associated with endothelial damage. We measured the urinary levels of 8-iso-PGF2alpha and nitric oxide metabolites as well as plasma sICAM-1 levels from healthy subjects after strictly controlled diets rich in either linoleic acid (LA, C18:2 n-6) or oleic acid (OA, C18:1 n-9). Thirty-eight volunteers (20 women and 18 men, mean age 27 years) consumed a baseline diet rich in saturated fatty acids (SFA) for 4 weeks and were then switched to either a high LA diet (11.5 en%) or a high OA diet (18.0 en%) also for 4 weeks. During the LA and OA diets, nearly all food was provided for the whole day. A control group of 13 subjects consumed their habitual diet throughout the study. Urinary excretion of 8-iso-PGF2alpha was significantly increased after the LA diet (170 vs 241 ng/mmol creatinine, P=0.04), whereas the urinary concentration of nitric oxide metabolites decreased (4.2 vs 2.6 mg/mmol creatinine, P=0.03). No significant changes were seen in the OA group. Significant differences between the LA and control group were found for both 8-oxo-PGF2alpha (P=0.03) and NO (P=0.02), whereas the OA and LA groups did not differ with respect to any parameter. Also plasma sICAM-1 remained unchanged in both groups throughout the study. In conclusion, the high-LA diet increased oxidative stress and affected endothelial function in a way which may in the long-term predispose to endothelial dysfunction.

Adult↗
PubMed1998

Functional food science and the cardiovascular system.

Cardiovascular disease has a multifactorial aetiology, as is illustrated by the existence of numerous risk indicators, many of which can be influenced by dietary means. It should be recalled, however, that only after a cause-and-effect relationship has been established between the disease and a given risk indicator (called a risk factor in that case), can modifying this factor be expected to affect disease morbidity and mortality. In this paper, effects of diet on cardiovascular risk are reviewed, with special emphasis on modification of the plasma lipoprotein profile and of hypertension. In addition, dietary influences on arterial thrombotic processes, immunological interactions, insulin resistance and hyperhomocysteinaemia are discussed. Dietary lipids are able to affect lipoprotein metabolism in a significant way, thereby modifying the risk of cardiovascular disease. However, more research is required concerning the possible interactions between the various dietary fatty acids, and between fatty acids and dietary cholesterol. In addition, more studies are needed with respect to the possible importance of the postprandial state. Although in the aetiology of hypertension the genetic component is definitely stronger than environmental factors, some benefit in terms of the development and coronary complications of atherosclerosis in hypertensive patients can be expected from fatty acids such as alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid. This particularly holds for those subjects where the hypertensive mechanism involves the formation of thromboxane A2 and/or alpha 1-adrenergic activities. However, large-scale trials are required to test this contention. Certain aspects of blood platelet function, blood coagulability, and fibrinolytic activity are associated with cardiovascular risk, but causality has been insufficiently proven. Nonetheless, well-designed intervention studies should be initiated to further evaluate such promising dietary components as the various n-3 and n-6 fatty acids and their combination, antioxidants, fibre, etc. for their effect on processes participating in arterial thrombus formation. Long-chain polyenes of the n-3 family and antioxidants can modify the activity of immunocompetent cells, but we are at an early stage of examining the role of immune function on the development of atherosclerotic plaques. Actually, there is little, if any, evidence that dietary modulation of immune system responses of cells participating in atherogenesis exerts beneficial effects. Although it seems feasible to modulate insulin sensitivity and subsequent cardiovascular risk factors by decreasing the total amount of dietary fat and increasing the proportion of polyunsaturated fatty acids, additional studies on the efficacy of specific fatty acids, dietary fibre, and low-energy diets, as well as on the mechanisms involved are required to understand the real function of these dietary components. Finally, dietary supplements containing folate and vitamins B6 and/or B12 should be tested for their potential to reduce cardiovascular risk by lowering the plasma level of homocysteine.

Blood Coagulation↗
PubMed1998

Role of red meat and arachidonic acid in protein kinase C activation in rat colonic mucosa.

Two studies were conducted to investigate the role of meat and arachidonic acid in colonic signal transduction, particularly protein kinase C (PKC) activation. In Study 1, 26 male Wistar rats were fed a casein- or a beef-based diet for four weeks. PKC activity was measured from the proximal and distal colonic mucosa and diacylglycerol concentration from fecal samples. The beef diet significantly increased membrane PKC activity in the proximal and distal colon and cytosolic PKC in the distal colon. No differences were found in fecal diacylglycerol concentration for the rats maintained on the two diets. In Study 2, 57 male Wistar rats were divided into three dietary treatment groups: a control group, a group supplemented with arachidonic acid at 8 mg/day (an amount equivalent to that available from the beef diet in Study 1), and a group supplemented with fish oil at 166 mg/day. After a four-week supplementation period, 6 rats per group were used for colonic phospholipid fatty acid analysis and 13 rats per group were used for analysis of colonic prostaglandin E2 concentration, sphingomyelinase, and PKC activities. Supplementation of dietary arachidonic acid resulted in incorporation of arachidonic acid into colonic phosphatidylcholine, which was associated with an increase in mucosal prostaglandin E2 concentration compared with the fish oil group. However, arachidonate supplementation had no effect on sphingomyelinase or PKC activities. These data indicate that meat significantly increases colonic PKC activity, but this effect is probably not due to the arachidonic acid content of meat.

Animals↗
PubMed1998

Similar effects of diets rich in stearic acid or trans-fatty acids on platelet function and endothelial prostacyclin production in humans.

The effects of stearic acid (C18:0) and trans-fatty acids (trans-FAs) on measures of platelet function and prostacyclin (PGI2) production are poorly understood in humans. In this controlled dietary study, platelet function and endothelial PGI2 production were studied in healthy humans after they consumed diets rich in C18:0 or trans-FAs. For 5 weeks, 80 subjects consumed a baseline diet high in saturated FAs and were then switched to a diet containing 9.3% of energy as stearic acid or a diet containing 8.7 energy% as trans-FAs from hydrogenated vegetable oils for another 5 weeks. All diets contained 32.2 to 33.9 energy% fat, 14.6 to 15.8 energy% saturated plus trans-FAs, 12.2 to 12.5 energy% cis-monounsaturated, and 2.9 to 3.5 energy% polyunsaturated FAs. No significant differences between the C18:0 and trans-FA diets were found in the urinary excretion of 2,3-dinor-thromboxane B2 or 2,3-dinor-6-keto-prostaglandin F1alpha. In vitro production of thromboxane B2 by platelets as well as urinary excretion of beta-thromboglobulin were also similar after both diets. Collagen-induced in vitro aggregation was significantly enhanced after the C18:0 diet compared with the trans-FA diet (P=.02), whereas no differences between the diets were found with ADP. The results indicate similar effects of C18:0 and trans-FA diets on platelet activation and endothelial PGI2 production.

Adult↗
PubMed1998

Replacement of dietary saturated by unsaturated fatty acids: effects of platelet protein kinase C activity, urinary content of 2,3-dinor-TXB2 and in vitro platelet aggregation in healthy man.

The present study was conducted to compare the effects of oleic (OA) and linoleic acids (LA) on platelet function in healthy subjects. After a 4-week period on a diet rich in saturated fatty acids (SAFA), 38 volunteers (20 female, 18 male) had a high OA (18.0 en%) diet or a high LA diet (11.5 en%) for four weeks in a controlled manner. A control group of 13 subjects consumed their habitual diet throughout the study. Replacing the SAFA diet by the OA or LA diet did not affect the membrane-associated activity of platelet protein kinase C (PKC). However, both diets tended to increase the cytosolic activity to a comparable extent. Both the OA and the LA diets increased urinary excretion of 2.3-dinor-TXB2, as compared to the SAFA diet, whereas the urinary excretion of beta-thromboglobulin remained unchanged. As compared to the initial SAFA diet, platelet aggregation to collagen increased after both diets, while ADP induced aggregation showed no diet-induced changes. The results indicate increased platelet activity after both oil diets with no differences between the OA and LA diet and confirm in vitro findings that cis-unsaturated fatty acids have a distinct effect on cytosolic PKC, in particular.

Adult↗
PubMed1997

Protein kinase C activation in rat colonic mucosa after diets differing in their fatty acid composition.

We studied the effects of different types of dietary fats on fatty acid composition and activity of protein kinase C (PKC) in rat colonic mucosa. Activation of PKC, a key enzyme in signal transduction and growth regulation, provides a mechanism by which dietary components could be involved in colon carcinogenesis. Male Wistar rats (n = 12/group) were fed a semisynthetic high fat diet (43% of energy) containing either sunflower oil, rapeseed oil, or butter for 4 weeks ad libitum. The control group received a low fat sunflower oil diet (10% of energy). The butter diet increased membrane-associated PKC activity in rat colonic mucosa compared with the low fat control diet (1237 vs. 917 pmol/min per mg prot.; P = 0.028). Mucosal fatty acids reflected dietary fatty acid composition even though there was no clear association between the amount of mucosal fatty acids and PKC activity. More research is needed to elucidate how dietary fatty acids regulate colonic PKC activity.

Animals↗
PubMed1997

Comparison between dietary monounsaturated and polyunsaturated fatty acids as regards diet-related diseases.

We have studied the effects of dietary fatty acid (FA) composition on lipids and lipoproteins, platelet function and other hemostatic variables as well as on the endogenous formation of DNA adducts of malonaldehyde (MA) in healthy subjects in controlled dietary experiments. The FAs studied were monounsaturated oleic acid (OA, 18:1 n-9), n-6-polyunsaturated linoleic acid (LA, 18:2 n-6), n-3 polyunsaturated alpha-linolenic acid (ALA, 18:3 n-3), and two long-chain, n-3 polyunsaturated FAs, eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3). The results indicated that a high OA and high LA diet had comparable effects on lipids and lipoproteins when they replaced saturated FAs in a diet. Furthermore, the effect of ALA did not differ from that of LA in this respect. Both diets also similarly increased in vitro platelet aggregation when compared with high saturated FA baseline diet. In another study the effect of LA and ALA on platelet function was studied. In this study ALA decreased in vitro platelet aggregation when compared with LA. When ALA was compared with EPA + DHA it was found that platelet function and some coagulation and fibrinolysis parameters were mainly affected in a similar manner by ALA and EPA + DHA treatments. The high LA diet increased the levels of DNA adducts of MA when compared with the effect of the high OA diet. Our findings indicate that the interpretation of the effect of diet, dietary fat or a specific FA on the development of chronic disease is extremely complex.

Arteriosclerosis↗
PubMed1997

Cis-unsaturated fatty acids and platelet function.

The main method to study platelet function in dietary studies has been the platelet aggregation test in vitro. Even though it is well established that dietary cis-unsaturated fatty acids (FAs) modify platelet aggregation some uncertainty still exists how to interpret the in vitro results in the context of a situation in vivo. The other ways to look at platelet activation are measurements of thromboxane metabolites in urine or the concentration of beta-thromboglobulin (betaTG) released from alpha-granules. Dietary fish oil or long-chain n-3 FAs lower the high basal excretion rate of thromboxane, while only a modest effect is noticed at a low basal excretion rate. Results on the effects of other cis-unsaturated FAs on urinary TXB2 metabolites are almost totally lacking. Furthermore, platelet betaTG release in vivo does not seem to be affected by changes in dietary FAs. The regulatory function of dietary FAs in platelets is extremely complex, and clearly more should be understood about the association between dietary FAs and platelet membrane FAs in connection with platelet responses to physiological stimuli and subsequent signal transduction inside the platelets.

Arachidonic Acids↗
PubMed1997

Stearic acid, trans fatty acids, and dairy fat: effects on serum and lipoprotein lipids, apolipoproteins, lipoprotein(a), and lipid transfer proteins in healthy subjects.

To compare the effects on serum lipoproteins of stearic acid, trans fatty acids, and dairy fat, 80 healthy subjects consumed a dairy fat-based (baseline) diet for 5 wk, then an experimental diet high in either trans fatty acids (8.7% of energy; n = 40) or stearic acid (9.3% of energy; n = 40) for another 5 wk. All diets provided 32.2-33.9% of energy as fat, 14.6-15.8% as saturated plus trans fatty acids, 11.4-12.5% as cis-monounsaturated fatty acids, 2.9-3.5% as polyunsaturated fatty acids, and 200-221 mg cholesterol/10 MJ. Compared with the dairy fat diet, stearic acid and trans fatty acids decreased serum total cholesterol concentrations similarly (by 13% and 12%, respectively, P < 0.001) but the trans fatty acid diet decreased HDL cholesterol (17%) and apolipoprotein (apo) A-I (15%) significantly more than did the stearic acid diet (11% and 12%, respectively). Stearic acid but not trans fatty acids reduced concentrations of LDL cholesterol and apo B significantly (P < 0.001). The trans fatty acid diet increased the ratio of LDL to HDL cholesterol (19%) and of apo B to apo A-I (16%) more than did the dairy fat diet (P < 0.001) but the stearic acid diet had no effect. Lipoprotein(a) concentrations increased with both experimental diets, significantly more with trans fatty acids (30%) than with stearic acid (10%). In conclusion, high amounts of trans fatty acids had more adverse effects on lipoproteins than did equal amounts of stearic acid and dairy fat. Stearic acid reduced LDL cholesterol, did not affect the ratio of LDL to HDL cholesterol, and increased lipoprotein(a), although to a lesser extent than did trans fatty acids. Dietary fats low in both saturated fatty acids and trans fatty acids should be favored.

Adult↗
PubMed1997

Alpha-linolenic acid and marine long-chain n-3 fatty acids differ only slightly in their effects on hemostatic factors in healthy subjects.

The effects of alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) on hemostatic factors were compared. Healthy subjects (29 women and 17 men aged 20-44 y) received either linseed oil (average ALA intake: 5.9 g/d) or fish oil plus sunflower oil (average EPA + DHA intake: 5.2 g/d) for 4 wk. The supplemented amount of fat was 1.19 mg/kJ (1 g/200 kcal) calculated energy expenditure. Stability of habitual diets was monitored. Blood samples were collected at baseline, at the end of the experimental period, and after a 12-wk follow-up period. Different changes in the study groups were seen only in serum cholesterol and triacylglycerols, platelet fatty acid composition, and ADP-induced platelet aggregation. The treatments did not differ in their effects on collagen-induced platelet aggregation and thromboxane production, aggregation to the thromboxane A2 mimic I-BOP, urinary excretion of 11-dehydro-thromboxane B2 and beta-thromboglobulin, bleeding time, plasma fibrinogen concentration, antithrombin III activity, factor VII coagulant activity, or activity of plasminogen activator inhibitor 1. The results indicate that supplemented ALA from vegetable oil and EPA and DHA from a marine source have largely parallel effects on hemostatic factors.

Adult↗
PubMed1997

Coagulation and fibrinolysis factors in healthy subjects consuming high stearic or trans fatty acid diets.

The effects of stearic acid (C18:0) and trans fatty acids on variables related to coagulation and fibrinolysis were studied in 80 healthy humans average age 29 +/- 9 years. All subjects consumed a baseline diet high in saturated fatty acids, mainly from dairy fat for 5 weeks. After this baseline diet they were allocated either to a diet high (8.7% of energy, En%) in trans fatty acids from partially hydrogenated vegetable oil (40 subjects) or a diet high (9.3 En%) in stearic acid (40 subjects) for 5 weeks. All diets contained 32.2-33.9 En% fat, 14.6-15.8 En% saturated plus trans fatty acids, 12.2-12.5 En% cis-monounsaturated and 2.9-3.5 En% polyunsaturated fatty acids and 216-250 mg/10 MJ cholesterol. The fats were mixed into solid foods and almost all daily food was provided. In comparison with the baseline dairy fat diet no change was observed in the concentrations of plasma fibrin degradation products and D-dimers. Also the factor VII coagulant activity (F VII:C), tissue type plasminogen activity (tPA) and plasminogen activator inhibitor activity (PAI-1) were not affected by the experimental diets. Small increase in plasma fibrinogen concentration during the stearic acid diet was statistically significant (from 3.49 to 3.63 g/l: p = 0.041), but probably without any biological significance. Both diets increased plasma level of lipoprotein Lp(a). It can be concluded that as far as coagulation and fibrinolysis are concerned there is no need to differentiate between stearic acid or trans monoenoic fatty acids.

Adult↗
PubMed1997

High dietary omega-6 polyunsaturated fatty acids drastically increase the formation of etheno-DNA base adducts in white blood cells of female subjects.

Lipid peroxidation generates reactive aldehydes such as trans-4-hydroxy-2-nonenal and malonaldehyde, which form promutagenic exocyclic DNA adducts in human cells and may contribute to diet-related cancers. Using ultrasensitive detection methods, analysis of WBC DNA from volunteers in a dietary study revealed that high intake of omega-6 polyunsaturated fatty acids increased malonaldehyde-derived adducts in male and female subjects. In contrast, etheno adducts (1,N6-ethenodeoxyadenosine; 3,N4-ethenodeoxycytidine) were not elevated in males but were, on average, 40 times higher in females, displaying a huge intersubject variation in lipid peroxidation-derived DNA damage. Exocyclic DNA adducts are promising biomarkers for examining the hypothesis of possible links between increased intake of dietary omega-6 polyunsaturated fatty acids, DNA damage, and elevated cancer risk for breast, colon, and prostate.

Adult↗
PubMed1996

Determination of DNA adducts of malonaldehyde in humans: effects of dietary fatty acid composition.

The effects of dietary fatty acid composition on the endogenous formation of DNA adducts of malonaldehyde (MA), the major product of lipid peroxidation, were investigated in humans. A group of 59 healthy individuals of both sexes and different ages was initially fed a milk fat-based diet rich in saturated fatty acids for 14 days. Following this initial period, after which the group was considered homogeneous with respect to diet, 30 randomly chosen subjects were given a sunflower oil-based (rich in polyunsaturated fatty acids) (SO) diet and the remaining 29 individuals a low erucic acid rapeseed oil-based (rich in monounsaturated fatty acids) (RO) diet for 25 days. The fatty acid composition of plasma lipid fractions and the level of DNA adducts of MA in total white blood cells were then determined at the end of the SO and RO dietary periods. DNA adduct levels were measured by 32p-postlabelling using reversed-phase HPLC with on-line detection of radioactivity. Higher concentrations of polyunsaturated fatty acids in plasma triglycerides and higher levels of DNA adducts of MA were found in the subjects on the SO diet when compared with those in the RO dietary group. A large inter-individual variation in adduct levels was observed. The average adduct level in the SO diet group was 7.4 +/- 8.7 adducts/10(7) nucleotides (n = 23). This level was 3.6-fold higher than that found in individuals in the RO diet group (P < 0.001). Our results, in conjunction with the mutagenic and carcinogenic properties of MA, thus suggest the interaction of lipid peroxidation products such as MA with DNA as one plausible mechanism explaining the involvement of dietary fat in carcinogenesis.

Adolescent↗
PubMed1996

Polyunsaturated fatty acids and platelet aggregation.

Platelets take part in haemostasis and thrombosis, and studies have been carried out to try to understand how dietary fatty acids could reduce platelet activation and thus the risk of cardiovascular disease. Unfortunately, many of these studies had serious methodological flaws, and the shortcomings in their study designs are probably the main reason for contradictory results in humans. The evidence concerning linoleic acid is not consistent, but intervention studies show increased platelet aggregation to various agonists after high-linoleic-acid diets. On the other hand, intake of alpha-linoleic acid either has no effect or leads to decreased platelet aggregation when compared with linoleic acid. High intake of long-chain n-3 fatty acids of fish or fish oils seems to usually decrease platelet aggregation. To date, there have not been many studies on the effect of platelet aggregation of small or reasonable amounts of n-3 fatty acids.

Coronary Disease↗
PubMed1996

Alpha-linolenic acid in rapeseed oil partly compensates for the effect of fish restriction on plasma long chain n-3 fatty acids.

OBJECTIVE: To examine the ability of alpha-linolenic acid (ALA) in low erucic acid rapeseed oil (RO) to compensate for the effects of a restriction in fish intake on plasma fatty acid composition. DESIGN AND SUBJECTS: Two times 6 weeks' randomized dietary intervention was used with blind crossover design in 40 healthy unconfined women and men (age 20-46y). INTERVENTIONS: Subjects were assigned to two fish restricted diets, namely RO diet and Trisun-sunflower oil (TSO) diet, with similar proportions of saturated : monounsaturated : polyunsaturated fatty acids (11.5:17.5:8.5% of total energy, En%), but differing in their ALA content (2.2 and 0.3 En%) and n-6 : n-3-ratio (3 : 1 and 23 : 1, respectively). The fatty acid compositions of plasma triglycerides (TG), cholesterol esters (CE), and phospholipids (PL) were analyzed by gas chromatography. Dietary intake was evaluated based on 3- to 7-day food records. RESULTS: The proportion of TG and CE ALA decreased on the TSO diet (from 1.6% to 0.9% and from 0.9% to 0.4%, respectively, P < 0.001) and increased on the RO diet (from 1.7% to 3.4% and from 0.9% to 1.3%, respectively, P < 0.001) compared to the baseline level. The proportion of eicosapentaenoic acid (EPA) in all three plasma fractions decreased on the TSO diet but not on the RO diet. The proportions of docosa-hexaenoic acid (DHA) decreased on both experimental diets and there was no difference in CE DHA between the diets. PL docosa-pentaenoic acid (DPA) and PL DHA remained at a higher level on the RO diet compared to the TSO diet (P < 0.001 and P < 0.05, respectively). CONCLUSIONS: ALA is metabolized to EPA in humans to a significant extent. The degree to which rapeseed oil (ca 50g/day) affects the proportion of EPA resembled the effect of a weekly portion (50-100g) of fatty fish depending on the fat content of the fish.

Adult↗