Joel M. Evans, MD reviews recent literature on topics such as St. John’s wort, Alzheimer’s disease and dietary fiber intake.

by Joel M. Evans, MD 

St John’s wort for major depression.
Linde et al., Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000448


BACKGROUND: In some countries, extracts of the plant Hypericum perforatum L. (popularly called St. John’s wort) are widely used for treating patients with depressive symptoms. OBJECTIVES: To investigate whether extracts of hypericum are more effective than placebo and as effective as standard antidepressants in the treatment of major depression; and whether they have fewer adverse effects than standard antidepressant drugs. SEARCH STRATEGY: Trials were searched in computerised databases, by checking bibliographies of relevant articles, and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were included if they: (1) were randomised and double-blind; (2) included patients with major depression; (3) compared extracts of St. John’s wort with placebo or standard antidepressants; (4) included clinical outcomes assessing depressive symptoms. DATA COLLECTION AND ANALYSIS: At least two independent reviewers extracted information from study reports. The main outcome measure for assessing effectiveness was the responder rate ratio (the relative risk of having a response to treatment). The main outcome measure for adverse effects was the number of patients dropping out due to adverse effects. MAIN RESULTS: A total of 29 trials (5489 patients) including 18 comparisons with placebo and 17 comparisons with synthetic standard antidepressants met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In nine larger trials the combined response rate ratio (RR) for hypericum extracts compared with placebo was 1.28 (95% confidence interval (CI), 1.10 to 1.49) and from nine smaller trials was 1.87 (95% CI, 1.22 to 2.87). Results of trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), respectively, RRs were 1.02 (95% CI, 0.90 to 1.15; 5 trials) and 1.00 (95% CI, 0.90 to 1.11; 12 trials). Both in placebo-controlled trials and in comparisons with standard antidepressants, trials from German-speaking countries reported findings more favourable to hypericum. Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (odds ratio (OR) 0.24; 95% CI, 0.13 to 0.46) or SSRIs (OR 0.53, 95% CI, 0.34-0.83). AUTHORS’ CONCLUSIONS: The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

My Comment:
This is an important article because it comes from the prestigious Cochrane database. This particular study is a review of the world’s literature on St. John’s wort and major depression, looking to compare it to standard antidepressants in the areas of effectiveness and side effects. In summary, they found that St. John’s wort was superior to both placebo and antidepressants (same effectiveness with fewer side effects) in the treatment of major depression. This is even more important because:

(1) the NIH National Center for Complementary and Alternative Medicine published a multi-center study that found St. John’s wort (as well as the anti depressant sertraline) was not effective in the treatment of MILD depression. (JAMA. 2002 Apr 10;287(14):1807-14) and

(2) the NCCAM web site on St. John’s wort, accessed on November 2, 2008, states: “Scientific evidence regarding the effectiveness of St. John’s wort for depression is inconsistent. An analysis of the results of 37 clinical trials concluded that St. John’s wort may have only minimal beneficial effects on major depression. However, the analysis also found that St. John’s wort may benefit people with minor depression; these benefits may be similar to those from standard antidepressants. Overall, St. John’s wort appeared to produce fewer side effects than some standard antidepressants.”

Therefore, a reputable, independent analysis of the literature on St. John’s wort and depression shows its benefits as quite significant. It is my hope that this review will bring St. John’s wort to the forefront of the minds of holistic practitioners when considering interventions for depression. As a review, it is important to be aware of the effect of St. John’s wort on the CYP 450 system and the interactions with other medications, specifically oral contraceptives and other antidepressants.

Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial.
Lautenschlager et al., JAMA. 2008 Sep 3;300(9):1027-37

CONTEXT: Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking. OBJECTIVE: To determine whether physical activity reduces the rate of cognitive decline among older adults at risk. DESIGN AND SETTING: Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia. Assessors of cognitive function were blinded to group membership. PARTICIPANTS: We recruited volunteers who reported memory problems but did not meet criteria for dementia. Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate. A total of 170 participants were randomized and 138 participants completed the 18-month assessment. INTERVENTION: Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity. MAIN OUTCOME MEASURE: Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months. RESULTS: In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention. The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention. At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88). Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly. CONCLUSIONS: In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period.

My Comment:

As holistic practitioners, we are all aware of the myriad of health benefits associated with exercise. However, we may not be aware that the U.S. Department of Health and Human Services has just published (October 2008) a definitive set of physical activity guidelines for Americans, listing the health benefits of exercise as well as recommendations on how much exercise we need. These recommendations can be daunting for non exercisers, as the amount of exercise recommended for adults is 2 hours and 30 minutes a week of moderate-intensity or 1 hour and 15 minutes (75 minutes) a week of vigorous-intensity aerobic physical activity to achieve the listed health benefits.

This study showed that after six months of three 50 minute sessions of moderate physical activity per week (the exact recommendations found in the 2008 report), there was a modest improvement in cognition that was evident even 18 months after the conclusion of the study. This study adds to the literature showing the benefits of exercise for preventing cognitive decline, but most importantly shows how the benefits extend for a significant amount of time. This “factoid” is something that we all can use when discussing exercise and prevention of cognitive decline with our patients.

Dietary fiber intake in relation to coronary heart disease and all-cause mortality over 40 y: the Zutphen Study.
Streppel et al., Am J Clin Nutr. 2008 Oct;88(4):1119-25

BACKGROUND: Little is known about the effects of dietary fiber intake on long-term mortality. OBJECTIVE: We aimed to study recent and long-term dietary fiber intake in relation to coronary heart disease and all-cause mortality. DESIGN: The effects of recent and long-term dietary fiber intakes on mortality were investigated in the Zutphen Study, a cohort of 1,373 men born between 1900 and 1920 and examined repeatedly between 1960 and 2000. During that period, 1,130 men died, 348 as a result of coronary heart disease. Hazard ratios were obtained from time-dependent Cox regression models. RESULTS: Every additional 10 g of recent dietary fiber intake per day reduced coronary heart disease mortality by 17% (95% CI: 2%, 30%) and all-cause mortality by 9% (0%, 18%). The strength of the association between long-term dietary fiber intake and all-cause mortality decreased from age 50 y (hazard ratio: 0.71; 95% CI: 0.55, 0.93) until age 80 y (0.99; 0.87, 1.12). We observed no clear associations for different types of dietary fiber. CONCLUSIONS: A higher recent dietary fiber intake was associated with a lower risk of both coronary heart disease and all-cause mortality. For long-term intake, the strength of the association between dietary fiber and all-cause mortality decreased with increasing age.

My Comment:
There is tremendous literature on the relationship of fiber intake and health. Some is controversial (for some), such as fiber’s association with colon cancer. Other literature reveals benefits that are not contested, such as the benefits of fiber in preventing constipation. This paper is important because it comes from the Zutphen Study, a lengthy longitudinal study of over 1,300 men aged 40-60 years and examined repeatedly for 40 years (to age 80-100), where multiple factors relating to  health, morbidity and mortality were studied.  In this particular paper, the relationship of fiber intake to heart disease and all-cause mortality was studied. The authors found a significant association between higher fiber intake and a reduction in both CAD and all-cause mortality, describing a 17% reduction in CV mortality and a 9% reduction in all-cause mortality for each additional 10 grams of daily fiber intake. Though the protective effect of fiber decreased after age 50, it was still present. I feel strongly that stressing the importance of fiber in the diet is one of the most important nutritional strategies to recommend to patients, and unfortunately, all too often it falls below the radar screen.

The Role of Oral Coenzyme Q10 in Patients Undergoing Coronary Artery Bypass Graft Surgery.
Makhija et al.,  J Cardiothorac Vasc Anesth. 2008 Jun 5. [Epub ahead of print]

OBJECTIVE: Cardiopulmonary bypass (CPB) is known to induce oxidative stress. Because total antioxidant level is reduced during CPB, the supplementation of an antioxidant might help in attenuating the oxidative stress response. The authors sought to evaluate the efficacy of oral coenzyme Q10, in attenuating the oxidative stress to CPB and altering the clinical outcome in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, randomized, single-center clinical study. SETTING: A cardiothoracic center of a tertiary hospital. PARTICIPANTS: Thirty patients scheduled for elective CABG surgery. INTERVENTIONS: The study group (n = 15) received oral coenzyme Q10, 150 to 180 mg/d, for 7 to 10 days preoperatively, whereas the control group (n = 15) did not receive any antioxidant or placebo. The anesthesia technique was standardized in both groups. Blood samples for total antioxidant level, blood glucose level, and clinical outcome parameters up to 24 hours postoperatively were compared. MEASUREMENTS AND MAIN RESULTS: There was no difference in the antioxidant level between the 2 groups at any point of time. However, in the study group, 24 hours after aortic clamp release, it was significantly higher than baseline (p < 0.05). The blood glucose was significantly lower in the study group at aortic clamp removal and 4 hours after clamp removal as compared with the control group (p = 0.01). The study group had significantly fewer reperfusion arrhythmias, lower total inotropic requirement, mediastinal drainage, blood product requirement, and shorter hospital stays compared with the control group. CONCLUSION: Oral coenzyme Q10 therapy for 7 to 10 days preoperatively could improve clinical outcome in patients undergoing CABG surgery. A larger study group is recommended for confirmation.

My Comment:

The cardiovascular benefits of Coenzyme Q10 are well known. This study shows how beneficial CoQ10 is for patients about to have coronary bypass graft surgery (CABG). This is important both because of the fear-based blanket rejection by some surgeons and anesthesiologists to all preoperative supplements, as well as the documented benefits in a population that is at high risk for peri-operative complications.

The study, though small in numbers, showed that giving patients COQ10 seven to ten days before surgery resulted in a decrease in common complications and led to a shorter post operative stay in the hospital. The authors correctly recommend a larger study, and this protocol would not be of benefit for those patients that have CABG surgery on an emergency basis. However, for those that have seven to ten days to prepare for surgery, this article provides the intellectual foundation to consider COQ10 supplementation. In my practice, which does not involve acute care for cardiovascular issues, this article serves as a reminder of the importance of putting my patients with CV disease on COQ10, as an acute coronary event is not always predictable. If surgery is required, I would prefer to have my patients already on COQ10. Of course, many of you reading this are thinking that COQ10 would hopefully prevent acute cardiac events, and I wholeheartedly agree.

Joel M. Evans, MD is Assistant Clinical Professor of Obstetrics, Gynecology and Women’s Health at Albert Einstein College of Medicine, Founder and Director, The Center for Women’s Health in Stamford, CT and author of The Whole Pregnancy Handbook (Gotham 2005).

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