Twelve Weeks of Additional Fish Intake Improves the Cognition of Cognitively Intact, Resource-Limited Elderly People: A Randomized Control Trial.

INTRODUCTION: Dietary omega 3 polyunsaturated fatty acids (PUFA) may reduce the risk of dementia. Many studies have investigated PUFA supplementation in high-income countries, yet food-based randomized control trials using omega 3 PUFA rich fish in lower to middle income countries, are lacking. OBJECTIVE: To determine the effect on cognition of adding either fish or non-fish foods for twelve weeks to an enhanced diet of cognitively intact, independently living, resource-limited elderly people. DESIGN: Randomized control trial (National Health Trial register: DOH-27-061-6026). SETTING: Retirement center in urban South Africa. PARTICIPANTS: Fifty-seven (74% female, mean age: 72±7 years) elderly participants with cognitive function exceeding 22 on the Mini Mental State Examination were randomized into an intervention (n=31) and control (n=26) group. INTERVENTION: The usual diets of both groups were enhanced with context-appropriate foods to mimic elements of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. The intervention group additionally received canned pilchards and fish spread every week amounting to an additional (theoretical) intake of 2.2g omega 3 PUFA daily. The control group received canned meatballs and texturized soya every week. MEASUREMENTS: Cognition was measured twice before and once after the intervention phase using the Cognitive Abilities Screening Instrument (CASI). Adherence was assessed by a study-specific food frequency questionnaire and red blood cell (RBC) PUFA biomarkers. Data were analyzed using a non-parametric analysis of covariance (ANCOVA) with, and without, bootstrap imputation. RESULTS: Participants in the intervention group had a significantly higher post intervention (P=0.036) CASI score than the control group, when the model was fitted with imputation and controlled for baseline scores. Participants in the intervention group also had a significantly higher intake of calculated dietary omega 3 PUFA and higher levels of RBC eicosapentaenoic acid and docosapentaenoic acid content than the control group (P < 0.05). CONCLUSION: Twelve weeks of fish intake in the context of a modified MIND diet may improve the cognition of cognitively intact, resource-limited elderly people.

Allergic sensitisation in South Africa: Exploring regional variation in sensitisation.

BACKGROUND: Allergy is a common health problem in South Africa (SA), and a rational approach to allergy testing is essential to ensure cost-effective as well as optimal patient diagnosis and management. OBJECTIVES: To review allergy testing data with respect to current national testing recommendations, and to explore the regional variations in sensitisation. METHODS: Retrospective data review on allergy testing from a private pathology provider in SA over a 2-year period. Data on skin-prick testing (SPT) and allergen-specific IgE testing originating from all the provinces of SA were collected and analysed with regards to allergen positivity rate and regional sensitisation patterns. RESULTS: Among the patients (N=45 0320) tested for a suspected inhalant allergy, 46% tested positive. Only 45% of these received additional testing for the nine recommended inhalant allergens included in the current national testing protocol. Among the patients (N=6 775) who received SPT for a suspected inhalant allergy, 59% yielded one or more positive results. The most frequent sensitising allergens were house dust mite (Dermatophagoides pteronyssinus) and grass pollen. The house dust mite, Blomia tropicalis, was a significant sensitiser in coastal regions. SPT identified two other important regional allergens which are not included in the current recommendations for inhalant allergen-specific IgE testing. CONCLUSIONS: The current diagnostic recommendations include allergens that demonstrate significant sensitisation in all regions of SA. Two additional allergens that show significant regional sensitisation in the South African population were identified. These findings may aid the recommendations for the most appropriate and cost-effective approach to allergy testing of symptomatic patients in SA.

Effect of metformin therapy and dietary supplements on semen parameters in hyperinsulinaemic males.

Previous reports indicated that hyperinsulinaemic men may exhibit a higher percentage of poorly compacted DNA in their spermatozoa and less success in an IVF programme (Andrologia, 45, 2003, 18; Andrologia, 2014, doi: 10.1111/and.12227). The aim of this study was to investigate the effect of metformin (Glucophage®) and antioxidant treatment (StaminoGro®) on the semen parameters of hyperinsulinaemic men. Nineteen hyperinsulinaemic male patients were treated for 3 months with metformin alone (Group A), and fifteen patients used metformin in combination with the nutritional supplement (Group B). Combined data of the two groups (pre- and post-treatment) differ significantly regarding sperm morphology (P = 0.0003) and CMA3 (P < 0.0001) values. The improvement in sperm morphology after treatment was similar for the two respective groups (P < 0.05). The morphological normal sperm forms increased from the mean percentage of 3.9 to 5.5% and from 4.2 to 5.5% for Group A and B respectively. Where a combination of metformin and the supplement were used (Group B), the combination treatment proved to be superior in obtaining enhanced chromatin packaging quality although not statistically significant (P = 0.5929) when compared with the metformin (Group A) group. The chromatin packaging quality in Group B improved with 10% while the improvement in Group A was approximately 8.3%. Therefore, infertile hyperinsulinaemic men can benefit from metformin treatment and should be advised on the use of nutritional supplements with antioxidant properties.

Effect of exercise versus relaxation on haemoglobin A1C in Black females with type 2 diabetes mellitus.

BACKGROUND: Evidence suggests that populations in Africa develop Type 2 diabetes mellitus (DM) at an increasing rate as they reject their traditional lifestyles. Diabetes is the tenth most common cause for total life years lost in females in South Africa. Physical activity is under-used in the management of type 2 DM in South Africa. AIM: To investigate the efficacy of an exercise intervention programme compared to relaxation exercises to decrease HbA1c over a period of 12 weeks, in type 2 DM female subjects. DESIGN: Single blind, double-intervention randomized trial. METHODS: Clinical measurements were done before and after the 12-week exercise and relaxation interventions. The interventions consisted of education and aerobic exercise for the exercise group, and education and relaxation for the second group. RESULTS: Adjusted baseline HbA1c change from baseline in the exercise group after 12 weeks was -0.39% (95%CI -0.80 to 0.02) and in the relaxation group -0.97% (95%CI -1.38 to 0.55) (p = 0.052). The results for the BMI were -0.07% kg/m2 (95%CI -0.2 to 0.14) in the exercise group versus -0.23 kg/m2 (95%CI -0.44 to 0.02) in the relaxation group (p = 0.28). The difference from baseline in distances covered following the 6 min walk test was statistically significantly greater (p < 0.01) in the exercise group: 46.76 m (95%CI 36.20-57.32) vs the relaxation group 22.7 m (95%CI 12.07-33.33). DISCUSSION: The exercise intervention failed to reduce the HbA1c to a greater extent than in the relaxation control group. Both groups improved significantly from baseline, probably due to the study effect.

Will an increased dietary folate intake reduce the incidence of cardiovascular disease?

Based on a meta-analysis of published studies, it has been estimated that approximately 10% of coronary artery disease cases are attributable to hyperhomocyst(e)inemia. It has also been calculated that food fortification with folate might reduce the number of cases of coronary artery disease in the United States by 50,000 per year. However, the use of statistical concepts to estimate the expected benefits of this intervention strategy may be misleading.

Effective homocysteine metabolism may protect South African blacks against coronary heart disease.

L-Methionine (0.1 g/kg body wt) was administered to young white [n = 18; mean (+/- SD) age 20.0 +/- 1.0 y] and black [n = 12; mean (+/- SD) age 22.0 +/- 1.3 y] volunteers who had a similar lifestyle and who did not differ significantly from each other with respect to plasma folate or vitamin B-12 concentrations. Blacks, however, had significantly lower plasma pyridoxal-5'-phosphate concentrations compared with whites (P < 0.001). Fasting plasma homocysteine concentrations in blacks and whites were not significantly different. The mean (+/- SD) maximum increase in plasma homocysteine concentration measured after methionine loading was significantly lower (P < 0.01) in blacks (11.0 +/- 3.6 mumol/L) than in whites (18.0 +/- 6.2 mumol/L). Six weeks of vitamin supplementation (1.0 mg folic acid, 400 micrograms vitamin B-12, and 10 mg pyridoxine/d) reduced the mean (+/- SD) fasting plasma homocysteine concentration from 9.6 +/- 3.5 to 7.2 +/- 1.6 mumol/L in whites (P < 0.05) and from 8.4 +/- 2.4 to 5.6 +/- 1.4 mumol/L in blacks (P < 0.01). The mean (+/- SD) maximum increase in plasma homocysteine concentration after methionine loading declined from 18.0 +/- 6.2 to 11.1 +/- 2.3 mumol/L (P < 0.01) in whites, but vitamin supplementation did not have a significant effect on the methionine-load test in black volunteers. A significant race-by-time interaction shows that blacks metabolized homocysteine more effectively than did whites, which may partly explain their relative resistance against coronary heart disease despite a high prevalence of obesity, hypertension, and smoking.

Results of B-vitamin supplementation study used in a prediction model to define a reference range for plasma homocysteine.

Because high plasma concentrations of homocysteine constitute an enhanced risk for premature coronary heart disease, it is necessary to establish a reference range for normal concentrations of plasma homocysteine. The frequency distribution of plasma homocysteine concentrations tails to the right, and the nonparametric approach is unsatisfactory for defining a normal plasma homocysteine reference range. By using subjects' responses to appropriate vitamin supplementation, we developed a mathematical prediction model to calculate the plasma homocysteine concentration that could be expected for each individual treated with a vitamin supplement. With this model, we can predict that plasma homocysteine concentrations will approach a normal frequency distribution with a 95% reference range (mean +/- 2 SD) of 4.9-11.7 mumol/L, provided the vitamin status of the study population is improved.

Vitamin requirements for the treatment of hyperhomocysteinemia in humans.

We have previously shown that a modest vitamin supplement containing folic acid, vitamin B-12 and vitamin B-6 is effective in reducing elevated plasma homocysteine concentrations. The effect of supplementation of the individual vitamins on moderate hyperhomocysteinemia has now been investigated in a placebo-controlled study. One hundred men with hyperhomocysteinemia were randomly assigned to five groups and treated with a daily dose of placebo, folic acid (0.65 mg), vitamin B-12 (0.4 mg), vitamin B-6 (10 mg) or a combination of the three vitamins for 6 wk. Folic acid supplementation reduced plasma homocysteine concentrations by 41.7% (P < 0.001), whereas the daily vitamin B-12 supplement lowered homocysteine concentrations by 14.8% (P < 0.01). The daily pyridoxine dose did not reduce significantly plasma homocysteine concentrations. The combination of the three vitamins reduced circulating homocysteine concentrations by 49.8%, which was not significantly different (P = 0.48) from the reduction achieved by folate supplementation alone. Our results indicate that folate deficiency may be an important cause of hyperhomocysteinemia in the general population.

Vitamin B-6 supplementation and theophylline-related effects in humans.

This study investigates whether vitamin B-6 supplementation reduces the stimulatory effects of theophylline (a pyridoxal kinase antagonist) on the nervous system. Twenty young, healthy adults entered this double-blind, randomized, crossover study but only 15 completed the experiment. The dependent measures were a battery of psychomotor tests, electrophysiological tests, and self-report questionnaires. Most tests, including spectral electroencephalography, aspects of the electromyograph, the Sternberg Test of information processing, and questionnaires of sleep quality and daytime sleepiness failed to distinguish between vitamin B-6 and placebo supplementation. However, theophylline-related tremor was markedly reduced (p < 0.01) with vitamin B-6 supplementation after a single dose of theophylline and a similar but nonsignificant trend was observed with repeated doses. There was a tendency for vitamin B-6 supplementation to reduce many side effects related to nervous system function. These findings suggest that vitamin B-6 supplementation with theophylline therapy may have some beneficial effects.

Pyelonephritis: renal urokinase activity in rats on essential fatty acid diets.

This study was undertaken to assess whether additions of different oils to the diets of male rats would affect the renal urokinase (UK) activity of healthy and pyelonephritic kidneys. Four groups of fatty acid diets were studied: fat-free, coconut oil, fish oil and evening primrose oil (EPO). Pyelonephritis was obtained by unilateral extrarenal urinary obstruction and subcutaneous injection of Escherichia coli. The UK activity of the non-obstructed kidneys did not differ statistically between rats infected and not infected with bacteria (P > 0.056), except within the coconut oil group. A statistically decreased UK activity was obtained with bacteria injected animals on a coconut oil diet (P < 0.0001). This phenomenon, namely a decrease in UK activity, was also seen with pyelonephritic kidneys of rats on fat-free, coconut and fish oil diets (P < 0.0065). However, the UK activity of the obstructed kidneys with and without infection in the EPO group remained similar (P = 0.8477). These results suggest that the UK activity in infection-induced renal stones may be restored by EPO containing diets and may be of high relevance in the prevention and treatment of infection-induced renal stones. This revelation now needs to be more fully investigated.

Theophylline increases pyridoxal kinase activity independently from vitamin B6 nutritional status.

Asthmatics treated with theophylline, a potent inhibitor of pyridoxal kinase and therefore a vitamin B6 antagonist, demonstrated a significant correlation (r = 0.71; p < 0.001) between drug plasma levels and erythrocyte pyridoxal kinase activities. A cross-over, placebo controlled study was completed on 15 healthy volunteers to investigate the mechanism by which theophylline induces pyridoxal kinase activity. The subjects were supplemented with vitamin B6 or placebo for two weeks before theophylline therapy was started. Vitamin B6 supplementation resulted in a four-fold increase in circulating pyridoxal 5'-phosphate levels, while placebo had no effect. When theophylline therapy was commenced, erythrocyte pyridoxal kinase activities increased significantly (p < 0.001) irrespective of whether vitamin B6 or placebo was supplemented. It is concluded that a depressed vitamin B6 status is not responsible for higher erythrocyte pyridoxal kinase activities encountered during theophylline therapy, but that the drug is directly responsible for elevated enzyme levels.

Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia.

We measured the vitamin B-6, vitamin B-12, and folic acid nutritional status in a group of apparently healthy men (n = 44) with moderate hyperhomocysteinemia (plasma homocysteine concentration > 16.3 mumol/L). Compared with control subjects (n = 274) with normal plasma homocysteine (< or = 16.3 mumol/L) concentrations, significantly lower plasma concentrations of pyridoxal-5'-phosphate (P < 0.001), cobalamin (P < 0.001), and folic acid (P = 0.004) were demonstrated in hyperhomocysteinemic men. The prevalence of suboptimal vitamin B-6, B-12, and folate status in men with hyperhomocysteinemia was 25.0%, 56.8%, and 59.1%, respectively. In a placebo-controlled follow-up study, a daily vitamin supplement (10 mg pyridoxal, 1.0 mg folic acid, 0.4 mg cyanocobalamin) normalized elevated plasma homocysteine concentrations within 6 wk. Because hyperhomocysteinemia is implicated as a risk factor for premature occlusive vascular disease, appropriate vitamin therapy may be both efficient and cost-effective to control elevated plasma homocysteine concentrations.

Relationship between vitamin B-6 status and elevated pyridoxal kinase levels induced by theophylline therapy in humans.

Theophylline administration to seven healthy male volunteers resulted in a rapid and significant decline in both plasma and erythrocyte pyridoxal-5'-phosphate levels. Total erythrocyte pyridoxal kinase levels increased during 15 wk of theophylline treatment from a mean initial activity of 19.23 +/- 5.03 (mean +/- SD) to 62.64 +/- 11.59 nmol pyridoxal-5'-phosphate formed/(g hemoglobin.h). Although plasma pyridoxal levels remained normal, the threefold increase in total erythrocyte pyridoxal kinase activity levels did not normalize plasma and erythrocyte pyridoxal-5'-phosphate levels. Pyridoxal-5'-phosphate hydrolysis was not affected by theophylline therapy. Increased pyridoxal oxidation was confirmed by elevated urinary 4-pyridoxic acid excretion after 15 wk of theophylline treatment. Mean erythrocyte alanine aminotransferase activity declined by 70%, and aspartate aminotransferase activity declined by 50%, indicating that decreased availability of pyridoxal-5'-phosphate can have widespread metabolic consequences. We conclude that the effect of theophylline on vitamin B-6 metabolism is not transitory and cannot be overcome by elevated intracellular levels of pyridoxal kinase. However, pyridoxine supplementation (10 mg/d for 1 wk) normalized indices of vitamin B-6 status and reversed the downward trend in both alanine aminotransferase and aspartate aminotransferase activity levels.

Genetic polymorphism of glutamate-pyruvate transaminase (alanine aminotransaminase): influence on erythrocyte activity as a marker of vitamin B-6 nutritional status.

A new, sensitive, two-step method free from interference by hemoglobin that measures erythrocyte glutamate-pyruvate transaminase (E-GPT) activity is described. Several aspects of E-GPT activity as an index of vitamin B-6 nutritional status were investigated with this method. 1) GPT shows a structural genetic polymorphism with two common alleles resulting in three phenotypes. In a population study (n = 92) E-GPT activity differed significantly (p less than 0.001) among the three phenotypic groups. Plasma pyridoxal-5'-phosphate concentrations in the three groups did not differ significantly. Therefore, E-GPT activity can only be used to assess vitamin B-6 nutritional status if GPT phenotype is accounted for. 2) Pyridoxine supplementation (10 mg/d) significantly (p less than 0.0001) increased E-GPT activity and decreased (p less than 0.0001) the percentage stimulation by pyridoxal-5'-phosphate in vitro although the absolute amount of in vitro stimulation by pyridoxal-5'-phosphate changed only marginally. 3) Inorganic phosphate inhibits in vitro activation of E-GPT by pyridoxal-5'-phosphate.

Glass ionomers and discoloration: a comparative study of the effects of tea and coffee on three brands of glass ionomer dental cement.

This study was undertaken to compare the in vitro discoloration of 3 brands of glass ionomer dental cement, Chemfil, Fuji Type II, and Ketac-Fil. Forty-eight specimens of each brand were prepared. Sixteen specimens of each brand were placed in tea, coffee and, as a control, water. Discoloration was evaluated by means of reflection spectrophotometry at 2, 4, 8, and 16 wk. Analysis of the data indicated that most discoloration occurred during the first 2 wk of immersion in the staining media and a little further discoloration took place between 2 and 16 wk (p less than 0.05). Tea discoloured glass ionomer more than did coffee (p less than 0.05) and Fuji Type II discoloured the most, Ketac-Fil the least whilst the discoloration of Chemfil lay between these two (p less than 0.05).

Evidence of a theophylline-induced vitamin B6 deficiency caused by noncompetitive inhibition of pyridoxal kinase.

A placebo-controlled, double-blind study indicated that theophylline administration to apparently healthy, young men induced significantly depressed plasma pyridoxal-5'-phosphate levels. Plasma pyridoxal levels were not affected by theophylline therapy. The effect of theophylline on circulating pyridoxal-5'-phosphate levels is explained by the observation that theophylline acts as a noncompetitive inhibitor for erythrocyte pyridoxal kinase (EC 2.7.1.35) with an apparent inhibition constant (Ki) of 1.28 x 10(-5) mol/L. Theophylline did not affect erythrocyte pyridoxamine (pyridoxine)-5'-phosphate oxidase (EC 1.4.3.5) activity. During theophylline therapy, erythrocyte pyridoxal kinase levels increased nearly twofold from an initial mean level of 24.2 +/- 4.0 (+/- SD) nmol to 46.9 +/- 7.3 nmol pyridoxal-5'-phosphate per gram of hemoglobin per hour. This partially counteracted the effect of theophylline on vitamin B6 metabolism. Nevertheless, erythrocyte pyridoxal-5'-phosphate levels in subjects given theophylline decreased significantly (p = 0.03) from pretreatment levels. The oral tryptophan load test resulted in significantly (p = 0.007) increased urinary xanthurenic acid excretion after 4 weeks of theophylline therapy. Both plasma pyridoxal-5'-phosphate levels and the tryptophan load test results normalized after 1 week of pyridoxine supplementation, indicating that 10 mg pyridoxine per day was effective to counteract the antagonistic effect of short-term theophylline therapy on vitamin B6 metabolism.

Vitamin B6 nutritional status in asthma: the effect of theophylline therapy on plasma pyridoxal-5'-phosphate and pyridoxal levels.

Plasma pyridoxal-5'-phosphate concentrations were significantly lower (p less than 0.001) in a group of 28 asthmatic women when compared to 33 controls. Plasma pyridoxal levels in the two groups were not different. Theophylline was administered to a group of 17 volunteers and resulted in large reductions in plasma pyridoxal-5'-phosphate levels, while plasma pyridoxal levels and urinary 4-pyridoxic acid excretion were unaffected by theophylline therapy. An in vitro study showed that theophylline did not interfere with the high performance liquid chromatography assay for pyridoxal-5'-phosphate, indicating that theophylline could affect liver metabolism of vitamin B6.

Effect of different levels of oral pyridoxine supplementation on plasma pyridoxal-5'-phosphate and pyridoxal levels and urinary vitamin B-6 excretion.

Plasma pyridoxal-5'-phosphate and pyridoxal levels increased significantly (p less than 0.05) when single, oral bolus doses of pyridoxine were increased from 10 to 25 and from 25 to 50 mg in nine female volunteers. However, when the dose was increased to 100 mg, plasma pyridoxal-5'-phosphate levels did not differ significantly from those recorded after the 50 mg dose. Within 3 h plasma pyridoxal levels rose with a factor of 3.85 compared with the 50 mg dose but high pyridoxal levels were eliminated from the circulation. Renal clearance of pyridoxal remained a constant, low percentage (less than 2.0%) of each pyridoxine supplement in spite of the observed very high circulating pyridoxal levels. Pyridoxine supplementation is discussed in relation to circulating pyridoxal-5'-phosphate and pyridoxal availability for cellular metabolism.