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Impact of Antioxidant Therapy on Symptoms of Anxiety and Depression. A Randomized Controlled Trial in Patients with Peripheral Arterial Disease
Abstract
The aim of this study was to determine the effect of an antioxidant preparation on the progression of peripheral arterial disease, and to identify any effects on mood. A randomized, placebo-controlled trial of antioxidant was performed in 120 men and women with intermittent claudication and an ankle brachial pressure index (ABPI) 0.9 in at least one limb. Patients were treated for 2 years with a preparation containing beta-carotene, ascorbic acid, pyridoxine, zinc sulphate and sodium selenite, or identical placebo. The Hospital Anxiety and Depression Scale, the ABPI, plasma cholesterol and walking distance were recorded at recruitment and after 2 years. Depression scores were slightly higher in the antioxidant group at baseline, but after 2 years this trend was reversed with significantly lower depression scores in the antioxidant group. There were no significant differences in anxiety scores between the two groups, but there was a trend towards less anxiety in the antioxidant group and more in those on placebo. Both groups showed small increases in cholesterol levels, and slight improvements in ABPI and walking distance, but these were not significant and did not correlate with anxiety or depression. An improvement in mood was demonstrated following antioxidant therapy, which was not related to improvement in underlying disease or explained by selective withdrawal from the trial.
Background
New research supports an integrated approach to treating depression, and lifestyle modifications should be a regular component of both preventative and treatment programs. Therefore, in order to investigate the relationship between various antioxidant supplements and depressive status, we carried out a meta-analysis of randomized controlled trials (RCT).
Methods
We thoroughly searched PubMed, Medline, Scopus, and Web of Science databases to screen publications focusing on the effects of antioxidant supplements on depression status. The meta-analysis mainly compared depression scores between groups that received antioxidant supplements and controls. We also pooled studies reporting changes in anxiety status as a secondary outcome.
Results
52 studies with 4049 participants were eventually identified. The meta-analysis found that the positive effect of antioxidant supplementation, such as magnesium (SMD = 0.16, p = 0.03), zinc (SMD = 0.59, p = 0.01), selenium (SMD = 0.33, p = 0.009), CoQ10 (SMD = 0.97, p = 0.05), tea and coffee (SMD = 1.15, p = 0.001) and crocin (MD = 6.04, p < 0.00001), on depressive status were all significant. And antioxidant supplementation also showed significant improvement in anxiety (SMD = 0.40, p < 0.00001). Subgroup analysis by scale types and countries were performed, and antioxidant supplementation's positive effects on depressive and anxiety states remained significant.
Limitations
This study did not limit the characteristics of the included population, and the diversity of scales also contributed to the heterogeneity.
Conclusion
Intake of antioxidant supplements is associated with improved depression and anxiety states, further affirms the therapeutic potential of antioxidant supplements as adjunctive therapy to conventional antidepressants.
Introduction:
To review the association between mental health and intermittent claudication (IC) perception, reporting and treatment in subjects with peripheral artery disease (PAD).
Evidence acquisition:
Literature searches of experimental and observational studies published up until 1.02.2016 were conducted using the following electronic databases: Medline/PubMed and Embase. The selection criteria for the studies included a population of patients diagnosed with peripheral artery disease who reported symptoms of intermittent claudication and were assessed for any psychopathological states (depression, anxiety, mood and personality disorders), which in turn were analysed with regard to the following: IC severity, symptom perception and reporting, patients' quality of life, treatment compliance and its effectiveness. The risk of bias was assessed using Cochrane Collaboration's tool and the Newcastle Ottawa Scales. The strength of recommendations was graded according to GRADE system.
Evidence synthesis:
The literature search identified 1598 citations, of which 13 studies with varying risk of bias were included in the review. Depression, anxiety, and personality types were described in more than 800 patients with peripheral arterial disease who suffered from intermittent claudication. With regard to IC perception and reporting, individuals with higher levels of depression had lower levels of pain acceptance, were more dissatisfied with their function and control over function and had a poorer quality of life. In the case of the type D personality, the results were not consistent. Studies assessing the influence of psychopathology on IC severity and treatment also showed discrepant results. Some studies indicated no differences between type D and non-type D patients with regard to the ankle brachial index (ABI) as well as pain free (PFWD) and maximal walking distances (MWD). On the other hand, others revealed that type D and depressed patients terminated 6MWT prematurely due to the onset of symptoms and experienced a greater annual decline in 6-minute walk distance, fast walking velocity and short physical performance battery. With regard to treatment adherence, patients with no mental problems made the best recoveries. Hostility, aggressiveness and affect-liability were the greatest obstacles to compliance.
Conclusions:
Mental disorders might influence the way in which the symptoms of the disease are reported, coped with, and treated. However, the results of the review preclude recommending a routine psychological examination as one of basic diagnostic procedures in patients with peripheral artery disease suffering from IC.
We studied biochemical measures of vitamin B-6, zinc, and copper in a group of 96 women and vitamin A and vitamin E concentrations in 89 women, all suffering from an eating disorder. Twenty-three control subjects were studied. Eating-disorder patients not taking vitamin or mineral supplements had significantly higher plasma concentrations of vitamins A and E than did control subjects (also not taking supplements). No difference was found in indices indicating vitamin B-6 status or in plasma zinc or copper concentrations. Self-induced vomiting was the only significant predictor of upper-quartile vitamin A concentrations. Upper-quartile vitamin B-6 activations (indicating lower vitamin B-6 activity) were significantly predicted only by low actual body weight. These results suggest that supplementation of micronutrient intake needs only to be considered for those eating-disorder patients at low weight and then only with water-soluble vitamins.
Interest in the antioxidant vitamin E as a possible protective nutrient against coronary disease has intensified with the recognition that oxidized low-density lipoprotein may be involved in atherogenesis.
In 1980, 87,245 female nurses 34 to 59 years of age who were free of diagnosed cardiovascular disease and cancer completed dietary questionnaires that assessed their consumption of a wide range of nutrients, including vitamin E. During follow-up of up to eight years (679,485 person-years) that was 97 percent complete, we documented 552 cases of major coronary disease (437 nonfatal myocardial infarctions and 115 deaths due to coronary disease).
As compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 (95 percent confidence interval, 0.50 to 0.87) after adjustment for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, including other antioxidants, had little effect on the results. Most of the variability in intake and reduction in risk was attributable to vitamin E consumed as supplements. Women who took vitamin E supplements for short periods had little apparent benefit, but those who took them for more than two years had a relative risk of major coronary disease of 0.59 (95 percent confidence interval, 0.38 to 0.91) after adjustment for age, smoking status, risk factors for coronary disease, and use of other antioxidant nutrients (including multi-vitamins).
Although these prospective data do not prove a cause-and-effect relation, they suggest that among middle-aged women the use of vitamin E supplements is associated with a reduced risk of coronary heart disease. Randomized trials of vitamin E in the primary and secondary prevention of coronary disease are being conducted; public policy recommendations about the widespread use of vitamin E should await the results of these trials.
Atherosclerosis and thrombosis may lead to cognitive impairment through cerebral infarcts or white matter hyperintensities. Oxidative stress is now seen as a major contributor to the process of atherogenesis. High intake of polyunsaturated fatty acids, e.g., linoleic acid, or low intake of antioxidants can increase oxidative stress. High intake of n-3 polyunsaturated fatty acids and its main source, fish, may reduce the risk of thrombosis. Little is known, however, about the relation between these dietary factors and cognitive function. The authors investigated this relation with data derived from a cohort of men, aged 69-89 years, who were participants in the Zutphen Elderly Study. The 30-point Mini-Mental State Examination was used to assess cognitive impairment in 1990 (score < or = 25 in 153/476 men, 32%) and cognitive decline from 1990 to 1993 (drop > 2 points in 51/342 men, 15%). Food intake was estimated in 1985 and 1990 by the cross-check dietary history method. High linoleic acid intake was associated with cognitive impairment after adjustment for age, education, cigarette smoking, alcohol consumption, and energy intake (odds ratio (OR) for highest vs. lowest tertile = 1.76, 95% confidence interval (CI) 1.04-3.01). Intake of n-3 polyunsaturated fatty acids was not associated with cognitive impairment, whereas high fish consumption tended to be inversely associated with cognitive impairment (OR = 0.63, 95% CI 0.33-1.21) and cognitive decline (OR = 0.45, 95% CI 0.17-1.16). Intakes of beta-carotene, vitamins C and E, and flavonoids were not inversely associated with cognitive impairment or decline. This study raises the possibility that high linoleic acid intake is positively associated with cognitive impairment and high fish consumption inversely associated with cognitive impairment.
# Dietary selenium: time to act {#article-title-2}
The essential trace element, selenium, which we largely obtain from bread and cereals, fish, poultry, and meat, plays a vital part in many metabolic functions. While new research increasingly suggests its relevance to disease prevention, evidence that dietary intake is falling in some parts of the world is giving cause for concern.
Selenium is a key component of a number of functional selenoproteins required for normal health. The best known of these are the antioxidant glutathione peroxidase enzymes, which remove hydrogen peroxide and damaging lipid and phospholipid hydroperoxides generated in vivo by free radicals and other oxygen derived species. If not removed, lipid hydroperoxides impair membrane structure and function1 and cause blood clotting disturbances by decreasing the production of prostacyclin while increasing the production of thromboxane.2 Furthermore, lipid hydroperoxides are not stable end products but, in the presence of transition metal ions, can decompose to give further reactive free radicals and cytotoxic aldehydes.3 Such secondary products may initiate more lipid peroxidation, promote atherosclerosis, damage DNA, and metabolically activate carcinogens.3
Selenium also plays an important role in the control of thyroid hormone metabolism. The iodothyronine deiodinases, which are responsible for the conversion of thyroxine (T4) to its active form, triiodothyronine (T3), are selenoenzymes.4 Selenium deficiency may cause reduced growth rates owing to a feedback response which …
The ability of animals or humans to control their consumption of energy in proportion to energy use has been recognized for some time (Kissileff and Van Itallie 1982). Less attention has been given to their ability to regulate intake of specific macronutrients. Although the roles of protein, carbohydrate, and fat in the body have been described and the amount of these nutrients needed daily has been established, consumption of foods has largely been regarded as motivated solely by the individual’s need for energy. For example, if an animal given rat chow diluted 50% with fat (so that it now contains only half as much protein or carbohydrate per gram), elects to eat abnormally large amounts of this food, the overconsumption is generally interpreted as reflecting an inability to control energy intake in the presence of a high-fat diet (Kissileff and Van Itallie 1982). The possibility that the animal is eating more of the food in order to consume a desired amount of protein or carbohydrate by consuming quantities large enough to compensate for the dilution of one or the other nutrient is usually not considered.
ABSTRACT– A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
Plasma tocopherol levels have been determined after single oral doses of two different tocopheryl acetate formulations. It was shown that a tablet preparation of D--tocopheryl acetate in a water dispersible form gave significantly higher plasma tocopherol than an equal dose of a conventional preparation of DL--tocopheryl acetate. — The normal plasma tocopherol of 38 healthy persons was found to be 11.3 4.28 g/ml. Atherosclerotic patients under oral treatment with 300–600 mg tocopheryl acetate daily for 0.5–6 years had a mean plasma concentration of 30.7 14.4 g tocopherol/ml (n = 65). — In 23 atherosclerotic patients suffering from intermittent claudication the muscle contents of tocopherol after treatment with vitamin E increased to averagely three times that of non-treated atherosclerotics. In a limited series studied there was a striking correlation between muscle tocopherol and the improvement of walking distance.Es wurde der Tocopherolgehalt m Plasma nach peroralen einmaligen Dosen von zwei verschiedenen Tocopherylacetat-Zubereitungen bestimmt. Es zeigte sich, da eine Tablettenzubereitung von D--Tocopherylacetat in einer in Wasser dispergierbaren Form einen wesentlich hheren Tocopherolgehalt im Plasma ergab, als die entsprechende Dosis eines konventionellen DL--Tocopherylacetat-Prparates. — Der normale Tocopherolgehalt im Plasma bei 38 gesunden Personen betrug 11.3 4.28 g/ml. Arteriosklerotische Patienten wiesen unter peroraler Behandlung mit 300–600 mg Tocopherylacetat tglich whrend 0.5–6 Jahren eine durchschnittliche Plasmakonzentration von 30.7 14.4 g Tocopherol/ml (n = 65) auf. — Bei 23 arteriosklerotischen Patienten mit intermittierendem Hinken war der Tocopherolgehalt in den Muskeln nach Behandlung mit Vitamin E im Durchschnitt dreimal grer als bei unbehandelten Arteriosklerotikern. In einer begrenzten Untersuchungsreihe konnte eine auffallende Korrelation zwischen dem Tocopherolgehalt in den Muskeln und der Verlngerung der Gehstrecke nachgewiesen werden.
The WHO/Rose Questionnaire on intermittent claudication was developed in 1962 for use in epidemiological surveys, and has been widely used. Several population studies have shown, however, that it is only moderately sensitive (60-68%), although highly specific (90-100%). In this study, reasons for the poor sensitivity and good specificity were determined following its application to 586 claudicants and to 61 subjects with other causes of leg pain. The results showed two important findings: firstly, that over half of the false negatives were produced by one question alone; and secondly that only three questions were required to maintain the specificity of the questionnaire. This knowledge, in conjunction with the pre-testing of additional questions, enabled a new questionnaire to be constructed: the "Edinburgh Claudication Questionnaire". This questionnaire was tested on 300 subjects aged over 55 years attending their general practitioner, and found to be 91.3% (95% CI 88.1-94.5%) sensitive and 99.3% (95% CI 98.9-100%) specific in comparison to the diagnosis of intermittent claudication made by a physician. The repeatability of the questionnaire after 6 months was excellent (kappa = 0.76, p < 0.001). These results suggest that this revised version of the WHO/Rose Questionnaire should be adopted for use in future epidemiological surveys of peripheral vascular disease.
Vitamin C (ascorbic acid) is an important anti-oxidant which may help to reduce free radical damage and atheroma formation in blood vessels. In a study in which a group of healthy volunteer subjects were followed up for 12 months and a group of patients with vascular disease taking Vitamin C supplements were followed for 23 months, we confirmed previous findings of seasonal variations in ascorbic acid and cholesterol and have shown an inverse relationship between leucocyte ascorbic acid and serum cholesterol levels. In healthy control subjects the increase in ascorbate and fall in cholesterol during the summer months was reversed when the weather changed to a more winter pattern, presumably due to dietary alterations. We found that ascorbic acid levels were lower in patients with peripheral vascular disease and that although normal ascorbic acid levels were achieved with Vitamin C supplementation, when supplements were stopped at the height of a normal summer, there was a fall in ascorbic acid and a rise in serum cholesterol to winter levels. Given these findings we suggest that patients with vascular disease should have Vitamin C supplements throughout the year.
The study was undertaken to estimate plasma copper and zinc in thirty-five depressed patients. Two blood samples were drawn from each patient, one before starting treatment and the second after recovery from depression. The results were compared with the thirty-five normal healthy individuals. The mean plasma copper in controls, depressed patients and in patients after recovery were 106.82, 122.14 and 104.22 micrograms/dl, respectively. The copper levels in patients when depressed were significantly higher as compared to controls and after recovery from depression. The mean plasma zinc levels in controls, depressed patients and after recovery were 115.80, 107.62 and 125.68 micrograms/dl, respectively. No significant difference could be obtained between control and depressed patients. However, the values were significantly higher in recovered patients compared to patients with depression.
An exploratory factor analysis of the HAD was carried out in 568 cancer patients. Two distinct, but correlated, factors emerged which corresponded to the questionnaire's anxiety and depression subscales. The factor structure proved stable when subsamples of the total sample were investigated. The internal consistency of the two subscales was also high. These results provide support for the use of the separate subscales of the HAD in studies of emotional disturbance in cancer patients.
The possibility that a subclinical deficiency of the trace element selenium might exist in a sample of the British population was examined by giving a selenium supplement for 5 weeks. Using a double-blind cross-over design, 50 subjects received either a placebo or 100 mcg selenium on a daily basis. On three occasions they filled in the Profile of Moods States. A food frequency questionnaire was used to estimate the intake of selenium in the diet. Intake was associated with a general elevation of mood and in particular, a decrease in anxiety. The change in mood when taking the active tablet was correlated with the level of selenium in the diet, which was estimated from a food frequency questionnaire. The lower the level of selenium in the diet the more reports of anxiety, depression, and tiredness, decreased following 5 weeks of selenium therapy. The results are discussed in terms of the low level of selenium in the food chain in some parts of the world.
To determine the effects of lowering cholesterol concentrations on total and cause specific mortality in randomised primary prevention trials.
Qualitative (meta-analytic) evaluation of total mortality from coronary heart disease, cancer, and causes not related to illness in six primary prevention trials of cholesterol reduction (mean duration of treatment 4.8 years).
24,847 Male participants; mean age 47.5 years.
Total and cause specific mortalities.
Follow up periods totalled 119,000 person years, during which 1147 deaths occurred. Mortality from coronary heart disease tended to be lower in men receiving interventions to reduce cholesterol concentrations compared with mortality in control subjects (p = 0.06), although total mortality was not affected by treatment. No consistent relation was found between reduction of cholesterol concentrations and mortality from cancer, but there was a significant increase in deaths not related to illness (deaths from accidents, suicide, or violence) in groups receiving treatment to lower cholesterol concentrations relative to controls (p = 0.004). When drug trials were analysed separately the treatment was found to reduce mortality from coronary heart disease significantly (p = 0.04).
The association between reduction of cholesterol concentrations and deaths not related to illness warrants further investigation. Additionally, the failure of cholesterol lowering to affect overall survival justifies a more cautious appraisal of the probable benefits of reducing cholesterol concentrations in the general population.
Plasma zinc levels were measured in 14 patients with primary affective disorder on admission to hospital; they were compared with plasma zinc levels in group of 14 age- and sex-matched controls. A significant difference in zinc levels was found between the 2 groups. Plasma zinc levels of 9 of the depressed patients on admission to hospital and at the point of discharge were compared; a significant increase in zinc levels was detected.
All measuring instruments require further validation both in the setting for which they were designed and in other fields. The Hospital Anxiety and Depression Scale was designed for detection and assessment of those mood disorders in the setting of hospital medical and surgical clinics. Reasons are given for supposing it has advantages over other similar scales. The present study undertakes a further validation of the scale in a general hospital setting. The opportunity is taken to assess the usefulness, in this setting of the Irritability Depression and Anxiety Scale and also of two subscales of the General Health Questionnaire, the one relating to the concept of depression and the other to the concept of anxiety. Score ranges of the latter two subscales are suggested and will require replication for confirmation of their usefulness.
Zinc is an essential trace element necessary for over 200 zinc metalloenzymes and required for normal nucleic acid, protein, and membrane metabolism. During the past two decades there has been a rapid expansion of knowledge concerning zinc metabolism in both normal and disease situations, including mechanisms for zinc absorption, excretion and internal redistribution of zinc after stress or trauma. Acrodermatitis enteropathica has been recognized to be a disease of impaired zinc absorption in man. A host of disease processes now are recognized to be complicated by zinc deficiency including alcoholic liver disease, sickle cell anemia, protein calorie malnutrition, and a variety of intestinal diseases including Crohn's disease, sprue, short bowel syndrome and after jejunal ileal bypass. Zinc has proved to be an extremely interesting mineral to nutritionists and physicians because of its importance in normal physiology and biochemistry and because of the diverse presenting features of zinc deficiency. This paper reviews ten functional consequences of zinc deficiency and emphasizes certain consequences in which there have been new discoveries concerning their mechanism (e.g., anorexia) or their clinical importance (e.g., immune dysfunction).
The known association between combined œstrogen-progestagen oral contraceptive (o.c.) administration and abnormalities of tryptophan and vitamin-B6 metabolism has been investigated in a group of 22 depressed women whose symptoms were judged to be due to the effects of o.c. 11 of these women showed biochemical evidence of an absolute deficiency of vitamin B6. In a double-blind crossover trial this group of women responded clinically to the administration of pyridoxine hydrochloride. The remaining 11 women showed no such response. Placebo administration was without effect. Possible mechanisms for depression due to o.c. use and its treatment with pyridoxine hydrochloride are discussed.
A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
Recent studies have both offered and contested the proposition that lowering plasma cholesterol by diet and medications increases suicide, homicide, and depression. Significant confounding factors include the quantity and distribution of dietary n-6 and n-3 polyunsaturated essential fatty acids that influence serum lipids and alter the biophysical and biochemical properties of cell membranes. Epidemiological studies in various countries and in the United States in the last century suggest that decreased n-3 fatty acid consumption correlates with increasing rates of depression. This is consistent with a well-established positive correlation between depression and coronary artery disease. Long-chain n-3 polyunsaturate deficiency may also contribute to depressive symptoms in alcoholism, multiple sclerosis, and post-partum depression. We postulate that adequate long-chain polyunsaturated fatty acids, particularly docosahexaenoic acid, may reduce the development of depression just as n-3 polyunsaturated fatty acids may reduce coronary artery disease.
This study investigates serum levels of zinc in 48 unipolar depressed subjects (16 minor, 14 simple major and 18 melancholic subjects) and 32 normal volunteers, and the relationships between zincemia and plasma neopterin levels, postdexamethasone adrenocorticotropic hormone and cortisol values, and anorexia-weight loss. Serum zinc levels were significantly lower in major depressed subjects than in normal controls, whereas minor depressed subjects showed intermediate values. There were significant negative correlations between serum zinc, and severity of depression and plasma neopterin concentrations. No significant relationships between zincemia and either postdexamethasone hormone values or anorexia/weight loss were found. The findings suggest that hypozincemia in major depression may be related to activation of cell-mediated immunity in that illness.
The aim of this study was to determine the levels of plasma fatty acids in patients with peripheral arterial disease and in control subjects and to identify whether any risks of disease related to these differences were influenced by smoking and antioxidant intake. A random sample of 1592 men and women aged 55 to 74 years was selected from the general population (the Edinburgh Artery Study), from which 153 cases of peripheral arterial disease were identified by the presence of intermittent claudication and low ankle systolic pressures at rest and during reactive hyperemia; these were matched by age and sex to 153 control subjects with no evidence of cardiovascular disease. In 113 case and 122 control subjects, fatty acid levels were measured in three plasma fractions (triglyceride, cholesteryl ester, and phospholipid), and smoking habits and dietary antioxidant intake were determined by questionnaire. Arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid (DPA/n-3) were significantly lower in the cases than controls (P < .01). More case than control subjects were current or exsmokers (86% versus 50%; P < .001), and the case subjects had lower vitamin C intake (64.8 mg versus 71.1 mg; P < .05). By logistic regression adjustment for smoking and vitamin C intake, only DPA/n-3 (odds ratio, 0.19; P < .01) and arachidonic acid (odds ratio, 0.44; P < .05) remained significantly related to disease; only DPA/n-3 reduced the risk associated with smoking. We conclude that in subjects with peripheral arterial disease compared with healthy control subjects, the largest differences occurred in fatty acids of the n-3 series, particularly DPA/n-3.(ABSTRACT TRUNCATED AT 250 WORDS)
The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse.
In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease.
After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease.
These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies.
In this study of 20 moderately to severely depressed patients, diagnosed using current research diagnostic criteria and excluding known bipolar affective disorder and reactive depression, we investigated relationships between severity of depression and levels and ratios of n-3 and n-6 long-chain polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids (PL). Severity of depression was measured using the 21-item Hamilton depression rating scale (HRS) and a second linear rating scale (LRS) of severity of depressive symptoms that omitted anxiety symptoms. There was a significant correlation between the ratio of erythrocyte PL arachidonic acid (AA) to eicosapentaenoic acid (EPA) and severity of depression as rated by the HRS (P < 0.05) and the LRS for depression (P < 0.01). There was also a significant negative correlation between erythrocyte EPA and the LRS (P < 0.05). The AA/EPA ratio in plasma PL and the ratio of erythrocyte long-chain (C20 and C22 carbon) n-6 to long-chain n-3 PUFA were also significantly correlated with the LRS (P < 0.05). These findings do not appear to be simply explained by differences in dietary intake of EPA. We cannot determine whether the high ratios of AA/EPA in both plasma and erythrocyte PL are the result of depression or whether tissue PUFA change predate the depressive symptoms. We suggest, however, that our findings provide a basis for studying the effect of the nutritional supplementation of depressed subjects, aimed at reducing the AA/EPA ratio in tissues and severity of depression.
Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.
Epidemiological evidence suggests that antioxidants protect against the development of atherosclerosis. To determine the effectiveness of antioxidant therapy in patients with lower limb atherosclerosis, a randomized placebo-controlled trial was performed in 120 men and women with intermittent claudication and an ankle/brachial pressure index (ABPI) < or = 0.9. The study was analysed on an intention-to-treat basis. After 2 years, there were no significant differences between antioxidant and placebo groups in plasma cholesterol, lipoproteins, haemostatic or rheological factors. However, after 6 months, low density lipoprotein cholesterol was significantly lower in those taking antioxidant (108.0 mg/dl compared with 120.1 mg/dl, p < 0.05). There were no differences in the ABPI or walking distance, although both groups improved slightly with time. The incidence of cardiovascular events and death was nonsignificantly lower in the antioxidant compared with the placebo group: event rates per year were 5.5% (95% CI 2.4-8.6) in the first year and 9.6% (95% CI 6.8-12.4) in the second year for those on antioxidants; and 7.7% (95% CI 5.1-10.3) and 13.3% (95% CI 8.9-17.7) respectively for those on placebo. Significantly fewer serious adverse events occurred in the antioxidant than the placebo group: 21.8% (95% CI 16.2-27.4) compared with 40.0% (95% CI 33.9-46.1). This study therefore suggests that although antioxidants may prevent cardiovascular events in patients with peripheral atherosclerosis, they do not improve lower limb function.
Hypozincaemia in depression
- D M Maes
- Pc Haese
- S Scharpe
- D M Maes
- Pc Haese
- S Scharpe
Functional consequences of zinc de® ciency
- Mcclain Cj
- Ej
- Allen
- Jj
McClain CJ, Kasarskis EJ, Allen JJ. Functional consequences of zinc de® ciency. Prog Food Nutr Sci 1985; 9: 185±226.
Hypozincaemia in depression
- M Maes
- D 'haese
- P C Scharpe