Contrarian current research outcomes

This blog entry is about three recent research results where the outcomes were the opposite of what might have been expected. 

1.     Chocolate consumption and depression are correlated 

The April 2919 publication Chocolate and Depressive Symptoms in a Cross-sectional Analysis indicates a surprising relationship between chocolate consumption and mood, namely that consumption and depression seem to be correlated.  “A sample of 1018 adults (694 men and 324 women) from San Diego, California, without diabetes or known coronary artery disease was studied in a cross-sectional analysis. The 931 subjects who were not using antidepressant medications and provided chocolate consumption information were the focus of the analysis. Mood was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Cut points signaling a positive depression screen result (CES-D score, 16) and probable major depression (CES-D score, 22) were used. Chocolate servings per week were provided by 1009 subjects. — Results  Those screening positive for possible depression (CES-D score 16) had higher chocolate consumption (8.4   servings per month) than those not screening positive (5.4 servings per month) (P = .004); those with still higher CES-D scores ( 22) had still higher chocolate consumption (11.8 servings per month) (P value for trend, <.01). These associations extended to both men and women. These findings did not appear to be explained by a general increase in fat, carbohydrate, or energy intake.” 

The study does not indicate a causal connection or, if one exists, direction of the cause.  Does eating chocolate induce depression or do depressed people eat more chocolate?  If it is the first case, the result is the opposite of what I would have thought.  In the second case, eating chocolate while feeling depressed seems completely understandable to me since I am a chocolate-eater.  I have mentioned health benefits of consuming chocolate in several blog entries.  For example, see Health and longevity benefits of dark chocolate. 

2.     Cognition and HIV HAART therapy

A rather interesting recent result is that cognition improves in AIDS patients when HAART therapy is discontinued.  HAART stands for highly active antiretroviral therapy and is normally administered as a cocktail of multiple antiretroviral drugs combined into a single pill.  For a long time it has been thought that anti-retroviral therapy in AIDS patients improves cognitive functioning.  For example. the 1999 publication Positive and sustained effects of highly active antiretroviral therapy on HIV-1-associated neurocognitive impairment reports for a sample of 26 patients” “Conclusion: HAART produces a positive and sustained effect on neurocognitive impairment in HIV-infected patients. A reduction of plasma viral load was associated with the regression of neuropsychological test abnormalities.” The recent result associated with discontinuation of HAART therapy again is the opposite of what was expected. 

The April 2010 publication Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort reports “Methods: Neurocognitive function was assessed as part of ACTG 5170, a multicenter, prospective observational study of HIV-infected subjects who elected to discontinue ART. Eligible subjects had CD4 count >350 cells/mm3, had HIV RNA viral load <55,000 cp/mL, and were on ART ( 2 drugs) for 6 months. Subjects stopped ART at study entry and were followed for 96 weeks with a neurocognitive examination. — Results: A total of 167 subjects enrolled with a median nadir CD4 of 436 cells/mm3 and 4.5 median years on ART. Significant improvements in mean neuropsychological scores of 0.22, 0.39, 0.53, and 0.74 were found at weeks 24, 48, 72, and 96 (all p < 0.001). In the 46 subjects who restarted ART prior to week 96, no significant changes in neurocognitive function were observed. — Conclusion: Subjects with preserved immune function found that neurocognition improved significantly following antiretroviral treatment (ART) discontinuation. The balance between the neurocognitive cost of untreated HIV viremia and the possible toxicities of ART require consideration.”   

It is interesting that the scores continued to improve during the 96 week period following discontinuation of the HAART therapy.  An important point is that the typical 2010 HAART therapy is different than the 1999 therapy and more effective in its anti-viral effects. So, it might be that one or more of the drugs in the 2010 HAART therapy that were not in the 1999 therapy are responsible for cognitive impairment.

3.     Vitamin-B therapy does not help diabetic nephropathy

We supplement-oriented types often have a default assumption that vitamin therapies are likely to have positive effects.     Specifically, B vitamins have been thought to be useful for treating neurological pathologies.  Not necessarily so, according to the April 2010 publication Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy.  “Context  Hyperhomocysteinemia is frequently observed in patients with diabetic nephropathy. B-vitamin therapy (folic acid, vitamin B₆, and vitamin B₁₂) has been shown to lower the plasma concentration of homocysteine.  Objective  To determine whether B-vitamin therapy can slow progression of diabetic nephropathy and prevent vascular complications.  Design, Setting, and Participants  A multicenter, randomized, double-blind, placebo-controlled trial (Diabetic Intervention with Vitamins to Improve Nephropathy [DIVINe]) at 5 university medical centers in Canada conducted between May 2001 and July 2007 of 238 participants who had type 1 or 2 diabetes and a clinical diagnosis of diabetic nephropathy.  Intervention  Single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B₆ (25 mg/d), and vitamin B₁₂ (1 mg/d), or matching placebo.  Main Outcome Measures  Change in radionuclide glomerular filtration rate (GFR) between baseline and 36 months. Secondary outcomes were dialysis and a composite of myocardial infarction, stroke, revascularization, and all-cause mortality. Plasma total homocysteine was also measured.  Results  The mean (SD) follow-up during the trial was 31.9 (14.4) months. At 36 months, radionuclide GFR decreased by a mean (SE) of 16.5 (1.7) mL/min/1.73 m² in the B-vitamin group compared with 10.7 (1.7) mL/min/1.73 m² in the placebo group (mean difference, –5.8; 95% confidence interval [CI], –10.6 to –1.1; P = .02). There was no difference in requirement of dialysis (hazard ratio [HR], 1.1; 95% CI, 0.4-2.6; P = .88). The composite outcome occurred more often in the B-vitamin group (HR, 2.0; 95% CI, 1.0-4.0; P = .04). Plasma total homocysteine decreased by a mean (SE) of 2.2 (0.4) µmol/L at 36 months in the B-vitamin group compared with a mean (SE) increase of 2.6 (0.4) µmol/L in the placebo group (mean difference, –4.8; 95% CI, –6.1 to –3.7; P < .001, in favor of B vitamins).  Conclusion  Among patients with diabetic nephropathy, high doses of B vitamins compared with placebo resulted in a greater decrease in GFR and an increase in vascular events.” GFR stands for  glomerular filtration rate, the best test to measure level of kidney function and determine the stage of  a kidney disease.  Lower is worse and scores below 15 indicate a pathology.  The B-vitamins did lower homocysteine but they also significantly lowered GFR indicating an overall negative effect in the population studied.

A few observations with respect to the life sciences and longevity:

·        Reasonable conjectures and conclusions might not be valid.

·        What we know we don’t know expands faster than what we know.  Uncertainty expands faster than the certainty. 

·         We have to live with that growing uncertainty.  For example, does eating chocolate cause depression or is that a good thing to do if you have depression?  In the past this was not something to be concerned about..