Clinical Briefs with Comments from Russell H. Greenfield, MD
Clinical Briefs
With Comments from Russell H. Greenfield, MD. Dr. Greenfield is Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC; and Visiting Assistant Professor, University of Arizona, College of Medicine, Tucson, AZ.
Four for 14: Health Behaviors and Mortality
Source: Khaw K-T, et al. Combined impact of health behaviours and mortality in men and women: The EPIC-Norfolk Prospective Population Study. PloS Medicine 2008;5:e12.
Goal: To quantify the combined impact of four well-supported health behaviors on mortality in the general community.
Study Design: Prospective population study (part of the 10-country EPIC trial - European Prospective Investigation into Cancer and Nutrition).
Subjects: Men and women aged 45-79, with no known cancer or cardiovascular disease at baseline, living in the general community of Norfolk, UK (data evaluable on n = 20, 244).
Methods: At baseline, subjects completed a detailed health and lifestyle questionnaire that included data on smoking, physical activity, alcohol intake, and social class. Physical examination was performed, including determination of body mass index (BMI), and blood samples were collected. Six months after study initiation, additional blood was drawn to ascertain vitamin C levels. Subjects were assigned a point total ranging from 0-4 based on the awarding of one point for each of the following health behaviors: current non-smoker; physically active; moderate alcohol intake; plasma vitamin C level > 50 mmol/L (indicative of fruit and vegetable intake of at least 5 servings per day).
Results: A total of 1,987 deaths occurred in the cohort. Each of the health behaviors (smoking, being inactive, not drinking alcohol in moderation, and low fruit and vegetable intake) was individually associated with significantly higher mortality risks from all causes. After adjustment for age, gender, social class, and BMI, and following an average of 11 years of follow-up, relative all-cause mortality risk (RR) was found to be inversely proportional to health behavior points in the following manner: compared with a score of 4 health behaviors, RR for 3, 2, 1, and 0 health behaviors was 1.39, 1.95, 2.52 and 4.04, respectively (P < 0.001 trend). The mortality risk for those with 4 health behavior points, as compared to those with 0 health behavior points, was equivalent to being 14 years younger in chronological age. Trends were most significant for cardiovascular causes of death.
Conclusion: Four straightforward health behaviors when combined predict a 4-fold difference in total mortality among middle-aged people in the general population, with an estimated impact equivalent to 14 years in chronological age.
Study strengths: Duration of follow-up; ability to identify all deaths in cohort with certainty; use of simple, pragmatic health behavior score.
Study weaknesses: Generalizability (almost 100% of participants were Caucasian); measurement performed at a single point in time, and health behaviors may have changed.
Of note: Norfolk is a rural-urban part of the United Kingdom representing a wide socioeconomic distribution; people with chronic disease are more likely to be physically inactive, but subjects with cancer, a history of stroke or cardiovascular disease were excluded from the main analyses (survival benefit was also noted for those with chronic ailments who adhered to healthy behaviors, however); prior data suggest that higher plasma levels of vitamin C predict lower all-cause mortality in the general population, and that a level of 50 mmol/L or more indicates an intake of at least five daily servings of fruits and vegetables; blood draws for vitamin C levels were delayed in this study until funding became available; low levels of work and leisure-time physical activity appear to predict higher levels of all-cause mortality and cardiovascular disease; the researchers did not feel that weighting of the different health behaviors was necessary; in the present cohort, vitamin supplement use was not associated with mortality risk.
We knew that: Lifestyle and dietary factors play a significant role in health and longevity; habits like smoking, physical activity, and diet are highly correlated, and often treated in research as covariates; existing data on alcohol intake suggest a U-shaped curve, with those who do not drink alcohol at all and those who imbibe heavily with the greatest mortality risk; data from the US Health Professionals Study showed that subjects adhering to five low-risk health behaviors (non-smoking, maintaining a BMI < 25 kg/m2, engaging in moderate physical activity on a regular basis, moderate alcohol intake, and relatively healthy diet score) had a 0.13 RR of ischemic heart disease compared with men who did not follow good health behaviors; in this trial, the lifestyle behavior with the single greatest impact was not smoking, followed by eating plenty of fruits and vegetables.
Comments: Even the lay public is well aware of the potential health benefits of the four health behaviors addressed in this paper not smoking, eating lots of fruits and vegetables, staying physically active, even drinking alcohol in moderation. Yet, they have almost always been considered in isolation from one another rather than as a collective set of actions. The findings of this paper are important for many reasons, but perhaps most because they point out that relatively modest behaviors can translate into major health benefits.
Many of our patients enter our offices feeling there is little they can do to optimize their chances for a long and healthy life. Yes, they know they shouldn't smoke, perhaps they should exercise more, but many hold onto somewhat fatalistic views ("My dad had it, and I'll likely get it, too."). Telling patients they can modulate their genetic predisposition towards certain ailments can be empowering; additionally, pointing out how relatively simple measures can literally add years to our lives might prove inspiring. Knowing that even those with chronic illness experienced benefit provides even more reason for optimism. The information contained in this paper can be used to further encourage our patients to take greater responsibility for their health and wellbeing, because the message is now both simple and convincing.
What to do with this article: Keep a hard copy in your file cabinet.
Hopes Dashed? Antioxidants and Down's Syndrome
Source: Ellis JM, et al. Supplementation with antioxidants and folinic acid for children with Down's syndrome: Randomized controlled trial. BMJ 2008;336:594-597.
Goal: To determine if supplementation with folinic acid, antioxidants, or both improves the language and psychomotor development of children with Down's syndrome.
Study Design: Randomized controlled trial with 2 X 2 factorial design.
Subjects: British infants with trisomy 21 under age seven months (evaluable data on n = 156).
Methods: Starting at a mean age of 4 months, subjects were daily given either 0.1 mg folinic acid, an antioxidant supplement (50 mg vitamin C, 100 mg vitamin E, vitamin A 0.9 mg, selenium 10 m, and zinc 5 mg), both folinic acid and the antioxidant supplement, or a placebo. Outcome measures included biochemical markers at age 12 months, and after 18 months of supplementation scores on the Griffiths developmental quotient and an adapted MacArthur communicative development inventory (to assess language development). Parents also recorded in a diary the date of major motor milestones.
Results: Even after adjustment for potential confounders, no differences between groups was identified for any of the clinical parameters measured, including biochemical markers. Supplementation also had no effect on attainment of major motor milestones.
Conclusion: Folinic acid and/or antioxidant supplementation in the concentrations employed in this study are of no discernible developmental benefit to children with Down's syndrome.
Study strengths: Low drop out rate; good compliance with protocol; effective blinding; compliance measurement.
Study weaknesses: Very low doses employed.
Of note: While advanced maternal age increases the risk for Down's syndrome, the majority of children with Down's syndrome are born to women under age 35 years; it is theorized that oxidative damage occurs in the brains of children with trisomy 21 due to accumulation of hydrogen peroxide secondary to increased superoxide dismutase activity; children with severe cardiac defects were excluded; the authors state that in spite of there being no significant supportive data for the use of vitamins and supplements for children with Down's syndrome, use is widespread among this population; Griffiths mental developmental scales combine observations on a child's interactions with test equipment together with developmental questions to parents, as well as subscales used to assess additional indices; 10/74 children taking antioxidants stopped doing so due to vomiting.
We knew that: With a birth prevalence of one in 1,000 live births, trisomy 21 (Down's syndrome) is the most common genetic cause of learning disability in the United Kingdom (in the United States, the prevalence is approximately one in 800 live births); about 4/10 children with Down's syndrome also have congenital heart defects; adults with Down's syndrome appear to age prematurely, with many showing changes compatible with those seen with Alzheimer's disease in the 3rd and 4th decades of life.
Comments: The authors are to be applauded for addressing the issue of supplementation in children with Down's syndrome, and especially for employing an intervention so early in life (average age 4 months). Unfortunately, the researchers were extremely cautious, likely over-cautious, in the nutrient dosages supplied to the children. This flaw drastically reduces the impact of the authors' conclusions. The study does have some significant strengths, especially as regards the prolonged administration of supplements to children with Down's syndrome, but does not answer the question of whether antioxidant and / or folate supplementation may ultimately benefit such children. The results show only that very low doses seem to provide no clear developmental benefit. Further trials are needed that use graded increases in the supplements, and better-defined forms of antioxidants, before this issue can be put to bed.
What to do with this article: Remember that you read the abstract.
Goal: To quantify the combined impact of four well-supported health behaviors on mortality in the general community.Subscribe Now for Access
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