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LE Magazine July 2005

Mediterranean diet

n-3 fatty acids and cancer therapy.

Supplementing the diet of tumor-bearing mice or rats with oils containing (n-3) (omega-3) or with purified (n-3) fatty acids has slowed the growth of various types of cancers, including lung, colon, mammary, and prostate. The efficacy of cancer chemotherapy drugs such as doxorubicin, epirubicin, CPT-11, 5-fluorouracil, and tamoxifen, and of radiation therapy has been improved when the diet included (n-3) fatty acids. Some potential mechanisms for the activity of (n-3) fatty acids against cancer include modulation of eicosanoid production and inflammation, angiogenesis, proliferation, susceptibility for apoptosis, and estrogen signaling. In humans, (n-3) fatty acids have also been used to suppress cancer-associated cachexia and to improve the quality of life. In one study, the response to chemotherapy therapy was better in breast cancer patients with higher levels of (n-3) fatty acids in adipose tissue [indicating past consumption of (n-3) fatty acids] than in patients with lower levels of (n-3) fatty acids. Thus, in combination with standard treatments, supplementing the diet with (n-3) fatty acids may be a nontoxic means to improve cancer treatment outcomes and may slow or prevent recurrence of cancer. Used alone, an (n-3) supplement may be a useful alternative therapy for patients who are not candidates for standard toxic cancer therapies.

J Nutr. 2004 Dec;134 (12 Suppl):3427S-3430S

Omega-3 fatty acids and inflammation.

Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune-modulating effects that may be of relevance to atherosclerosis and its clinical manifestations of myocardial infarction, sudden death, and stroke. The n-3 fatty acids that appear to be most potent in this respect are the long-chain polyunsaturates derived from marine oils, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and this review is restricted to these substances. A variety of biologic effects of EPA and DHA have been demonstrated from feeding studies with fish or fish oil supplements in humans and animals. These include effects on triglycerides, high-density lipoprotein cholesterol, platelet function, endothelial and vascular function, blood pressure, cardiac excitability, measures of oxidative stress, pro- and anti-inflammatory cytokines, and immune function. Epidemiologic studies provide evidence for a beneficial effect of n-3 fatty acids on manifestations of coronary heart disease and ischemic stroke, whereas randomized, controlled, clinical feeding trials support this, particularly with respect to sudden cardiac death in patients with established disease. Clinically important anti-inflammatory effects in man are further suggested by trials demonstrating benefits of n-3 fatty acids in rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders. Given the evidence relating progression of atherosclerosis to chronic inflammation, the n-3 fatty acids may play an important role via modulation of the inflammatory processes.

Curr Atheroscler Rep. 2004 Nov;6(6):461-7

Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial.

CONTEXT: The metabolic syndrome has been identified as a target for dietary therapies to reduce risk of cardiovascular disease; however, the role of diet in the etiology of the metabolic syndrome is poorly understood. OBJECTIVE: To assess the effect of a Mediterranean-style diet on endothelial function and vascular inflammatory markers in patients with the metabolic syndrome. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind trial conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III. INTERVENTIONS: Patients in the intervention group (n = 90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n = 90) followed a prudent diet (carbohydrates, 50%-60%; proteins, 15%-20%; total fat, <30%). MAIN OUTCOME MEASURES: Nutrient intake; endothelial function score as a measure of blood pressure and platelet aggregation response to l-arginine; lipid and glucose parameters; insulin sensitivity; and circulating levels of high-sensitivity C-reactive protein (hs-CRP) and interleukins 6 (IL-6), 7 (IL-7), and 18 (IL-18). RESULTS: After 2 years, patients following the Mediterranean-style diet consumed more foods rich in monounsaturated fat, polyunsaturated fat, and fiber and had a lower ratio of omega-6 to omega-3 fatty acids. Total fruit, vegetable, and nuts intake (274 g/d), whole grain intake (103 g/d), and olive oil consumption (8 g/d) were also significantly higher in the intervention group (P<.001). The level of physical activity increased in both groups by approximately 60%, without difference between groups (P =.22). Mean (SD) body weight decreased more in patients in the intervention group (-4.0 [1.1] kg) than in those in the control group (-1.2 [0.6] kg) (P<.001). Compared with patients consuming the control diet, patients consuming the intervention diet had significantly reduced serum concentrations of hs-CRP (P =.01), IL-6 (P =.04), IL-7 (P = 0.4), and IL-18 (P = 0.3), as well as decreased insulin resistance (P<.001). Endothelial function score improved in the intervention group (mean [SD] change, +1.9 [0.6]; P<.001) but remained stable in the control group (+0.2 [0.2]; P =.33). At 2 years of follow-up, 40 patients in the intervention group still had features of the metabolic syndrome,compared with 78 patients in the control group (P<.001). CONCLUSION: A Mediterranean-style diet might be effective in reducing the prevalence of the metabolic syndrome and its associated cardiovascular risk.

JAMA. 2004 Sep 22;292(12):1440-6

Adherence to a Mediterranean diet and survival in a Greek population.

BACKGROUND: Adherence to a Mediterranean diet may improve longevity, but relevant data are limited. METHODS: We conducted a population-based, prospective investigation involving 22,043 adults in Greece who completed an extensive, validated, food-frequency questionnaire at base line. Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet (range of scores, 0 to 9, with higher scores indicating greater adherence). We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality, as well as mortality due to coronary heart disease and mortality due to cancer, with adjustment for age, sex, body-mass index, physical-activity level, and other potential confounders. RESULTS: During a median of 44 months of follow-up, there were 275 deaths. A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality (adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score, 0.75 [95% confidence interval, 0.64 to 0.87]). An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease (adjusted hazard ratio, 0.67 [95% confidence interval, 0.47 to 0.94]) and death due to cancer (adjusted hazard ratio, 0.76 [95% confidence interval, 0.59 to 0.98]). Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant. CONCLUSIONS: Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality.

N Engl J Med. 2003 Jun 26;348(26):2599-608


Update on attention-deficit/hyperactivity disorder.

PURPOSE OF REVIEW: Attention-deficit/hyperactivity disorder (ADHD) is present in 3% to 10% of children in the United States. Children with ADHD can have academic impairments, social dysfunction, and poor self-esteem. There is also a higher risk of both cigarette smoking and substance abuse. Given this, the importance of treatment for ADHD needs to be underscored. This article will briefly review the diagnosis, etiology, and treatment of ADHD, with particular focus on nonstimulant medication and alternative treatment modalities. RECENT FINDINGS: Recent evidence suggests that the overall rate of medication treatment for ADHD has been increasing, with over 2 million children being treated with stimulants in 1997. With this increase, controversy has arisen over the possible association of stimulants with growth suppression. In addition, estimates indicate that as many as 30% of children with ADHD either do not respond to stimulant treatment or cannot tolerate the treatment secondary to side effects. This has lead to the consideration of treatment with both nonstimulant medications as well as alternative therapies, including diet, iron supplementation, herbal medications, and neurofeedback. Considering the various treatment options now available for ADHD, along with the complexity of the condition, clinical practice guidelines are emerging for the treatment of ADHD and will be discussed. SUMMARY: ADHD continues to be a serious health problem. Adequate treatment is needed to avoid academic impairments, social dysfunction, and poor self-esteem. This treatment includes consideration of stimulant medication, nonstimulant medication, as well as alternative therapies. The child with ADHD is likely better served with a mutimodal treatment plan, including medication, parent/school counseling, and behavioral therapy. Implementing an evidenced based algorithm for the treatment of ADHD may prove to be most effective.

Curr Opin Pediatr. 2004 Apr;16(2):217-26

Is attention-deficit/hyperactivity disorder an energy deficiency syndrome?

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable yet clinically heterogeneous syndrome associated with hypocatecholamine function in subcortical and prefrontal cortical regions and clinical response to medications that enhance catecholamine function. The goal of this article is to present a hypothesis about the etiology of ADHD by synthesizing these findings with recent experiments indicating that activity-dependent neuronal energy consumption is regulated by cortical astrocytes. The scientific literature was searched from 1966 to the present using MEDLINE and relevant key words. Inattention and impulsivity may be related to hypofunctionality of catecholamine projection pathways to prefrontal cortical areas, resulting in decreased neuronal energy availability. This may be mediated by astrocyte catecholamine receptors that normally regulate energy availability during neuronal activation. At least some forms of ADHD may be viewed as cortical, energy-deficit syndromes secondary to catecholamine-mediated hypofunctionality of astrocyte glucose and glycogen metabolism, which provides activity-dependent energy to cortical neurons. Several tests of this hypothesis are proposed.

Biol Psychiatry. 2001 Aug 1;50(3):151-8

Outcome-based comparison of Ritalin versus food-supplement treated children with AD/HD.

Twenty children with attention deficit/hyperactivity disorder (AD/HD) were treated with either Ritalin (10 children) or dietary supplements (10 children), and outcomes were compared using the Intermediate Visual and Auditory/Continuous Performance Test (IVA/CPT) and the WINKS two-way analysis of variance with repeated measures and with Tukey multiple comparisons. Subjects in both groups showed significant gains (p less than 0.01) on the IVA/CPT’s Full Scale Response Control Quotient and Full Scale Attention Control Quotient (p less than 0.001). Improvements in the four sub-quotients of the IVA/CPT were also found to be significant and essentially identical in both groups: Auditory Response Control Quotient (p less than 0.001), Visual Response Control Quotient (p less than 0.05), Auditory Attention Quotient (p less than 0.001), and Visual Attention Quotient (p less than 0.001). Numerous studies suggest that biochemical heterogeneous etiologies for AD/HD cluster around at least eight risk factors: food and additive allergies, heavy metal toxicity and other environmental toxins, low-protein/high-carbohydrate diets, mineral imbalances, essential fatty acid and phospholipid deficiencies, amino acid deficiencies, thyroid disorders, and B-vitamin deficiencies. The dietary supplements used were a mix of vitamins, minerals, phytonutrients, amino acids, essential fatty acids, phospholipids, and probiotics that attempted to address the AD/HD biochemical risk factors. These findings support the effectiveness of food supplement treatment in improving attention and self-control in children with AD/HD and suggest food supplement treatment of AD/HD may be of equal efficacy to Ritalin treatment.

Altern Med Rev. 2003 Aug;8(3):319-30

Efficacy of theophylline compared to methylphenidate for the treatment of attention-deficit hyperactivity disorder in children and adolescents: a pilot double-blind randomized trial.

Attention-deficit hyperactivity disorder (ADHD) is a common disorder of childhood that affects 3-6% of school children. Conventional stimulant medications are recognized as useful symptomatic treatments by both specialists and parents. Nevertheless, approximately 30% of ADHD children treated with them do not respond adequately or cannot tolerate the associated adverse effects. Such difficulties highlight the need for alternative, safe and effective medications in the treatment of this disorder. Theophylline is a psychomotor stimulant most widely used as a broncodilator. Purinergic modulation may be therapeutically beneficial in the treatment of psychiatric disorders. We hypothesized that theophylline would be beneficial for the treatment of ADHD and report results of a trial of theophylline compared with methylphenidate for the treatment of ADHD. A total of 32 children with ADHD as defined by DSM IV were randomized to theophylline and methylphenidate dosed on an age and weight-adjusted basis at 4 mg/kg/day (under 12 years) and 3 mg/kg/day theophylline (over 12 years) (group 1) and 1 mg/kg/day methylphenidate (group 2) for a 6-week double-blind and randomized clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist, at baseline and at 14, 28, and 42 days after start of the medication. No significant differences were observed between theophylline and methylphenidate on the Parent and Teacher Rating Scale scores over the trial (t = 0.49, d.f. = 24 P = 0.62 and t = 0.19, d.f. = 24 P = 0.54 respectively). Although the number of dropouts in the methylphenidate group was higher than the theophylline group, there was no significant difference between the two protocols in terms of the dropouts. In addition, headaches were observed more often in the methylphenidate group. The results suggest that theophylline may be a useful for the treatment of ADHD. In addition, a tolerable side-effect profile is one of the advantages of theophylline in the treatment of ADHD. Nevertheless, our study is small and our results would need to be confirmed in a larger study.

Clin Pharm Ther. 2004 Apr;29(2):139-44

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