non-animal protein diet dec inflammation

Another study found that a high vegetable diet decreases systemic inflammation, this time a vegan diet (see diet vegan dec inflam JAHA2018 in dropbox, or DOI: 10.1161/JAHA.118.0113670.)

Details:
--100 people with coronary artery disease (angiographically-defined, with >50% lesion in an artery >2mm caliber),  in open-label EVADE CAD study (Effects of a Vegan Versus the American Heart Association-Recommended Diet in Coronary Artery Disease), from 2014-17
--61 yo, 85% male, 92% white/7% black, 55% smokers (5% current), 64% htn/32% dyslipidemia/30% diabetic/30% prior MI/91% prior coronary revascularization
--94% on aspirin, 85% on  P2Y12 inhibitor (eg clopidogrel), 95% statin (57% on high-dose statin), 90% normal EF
    --overall, those on vegan diet were somewhat older than those on the AHA diet 
--groceries that conformed to these diets were provided to patients every week, along with either the Simply Vegan cookbook or the AHA low-fat, low-cholesterol cookbook
--patients had biweekly dietary recall on random days, and were seen at 4 weeks and 8 weeks (end of study)
--primary endpoint: high-sensitivity C-reactive protein concentration (hsCRP)
--secondary endpoints: 
    --inflammatory markers (WBC count and differential, WBC cellular adhesion molecules, markers of neutrophil activity, urine F-2-isoporostane/creatinine ratio)
    --anthropometric data (BMI, waist circumference), glycemic markers (fasting blood glucose, A1c, blood insulin levels), lipids
    --endothelium activity (using EndoPat machine)
--it should be noted that there were other changes in the diet: eg increased fiber in the vegan diet vs AHA diet (36 vs 25 g), and higher kcal (1715 kcal vs 1531 kcal), fat (56 vs 48 g), carbs (242 vs 170g), but lower protein (50 vs 80g),

Results:
--32% lower hsCRP in those on vegan diet vs AHA diet, b-statistic 0.68 (0.49-0.94), p=0.02 [b-statistic is the regression coefficient]
--33% lower after adjusting for age, race, baseline waist circumference, diabetes, prior MI,  b-statistic 0.67 (0.47-0.94), p=0.02
--no significant difference between diets in BMI or waist circumference, or markers of glycemic control
--nonsignificant 13% decrease in LDL on vegan diet, adjusted b-statistic 0.87 (0.78-0.97), p=0.01  [their prestudy cutpoint b-statistic for secondary outcomes was p<0.0015, though for primary outcome was p<0.05]
--no difference in measured endothelial function

Commentary:
--systemic inflammation (including that measured by hs-CRP levels) play an important role in atherosclerosis, and lowering the hs-CRP seems to lower the risk for major adverse cardiovasc events [though the drugs that lower CRP levels do have other potentially positive effects, eg on lipids, thrombosis, endothelial function, oxidative stress...]
    --even in interventional trials of specific dietary changes, it is near impossible to isolate the effects of individual components. is it the hsCRP change that decreases inflammation? or the higher fiber in that diet as in trial above (and other studies have found higher fiber diets do lower inflammation)? or some of the other differences in the diet composition? or some combination of lots of differences?
--up to 45% of patients with CAD continue to have elevated hsCRP levels (which may reflect continued increased atherosclerotic risk) despite taking anti-inflammatory therapy: eg, see the CANTOS study, where 91% were on statins, 95% on antithrombotic therapy, and hsCRP level was still 4.1. Additional specific anti-inflam meds did decrease both hsCRP and cardiac events: see cad CANTOS antiinflam helps nejm2017 in dropbox, or DOI: 10.1056/NEJMoa1707914). This study used a fully human monoclonal antibody against interleukin 1-b, a cytokine central to the inflammatory response that drives the interleukin-6 signaling pathway, so is likely to be more specific as an anti-inflammatory agent (it lowers interleukin-6 as well as CRP levels in other studies)
--there was another study done in 2006 where they gave a high vege diet that was high in plant sterols, soy protein, viscous fiber and almonds (vs the standard AHA diet then of low saturated fats, milled whole-wheat cereals, low-fat dairy). All patients had high LDL (mean 175 mg/dL). They found that the intervention diet was as good as the AHA diet coupled with the addition of lovastatin 20mg/d both in lowering LDL (8% decrease) and CRP (10% decrease). See dietary portfolio in dropbox, or Jenkins DJA, JAMA 2003; 290: 502
--several limitations to this study, which limit generalizability:
    --basically only white men
    --it was good they had an active comparator arm in the AHA diet, since there was similar intensity of interventions by nutritionists/researchers in both groups. but was the vegan diet as good as a Mediterranean diet in decreasing inflammation?? Or the DASH diet?? (eg see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412172/ , one of several studies finding decreased inflammatory markers with the Mediterranean diet, or see http://gmodestmedblogs.blogspot.com/2018/12/mediterranean-diet-dec-cad-and.html ) 
    --only 8 week study. and the issue with diets is that they are so hard to maintain longterm, especially in a high intensity society such as ours, with time and money constraints to eating well, and the omnipresent subliminal and upfront messaging/advertizing for unhealthy foods
    --and, of course, the big issue is that they could not assess real clinical outcomes, just presumed markers of disease

so, this study does add some useful information:
--a non-meat diet (as well as a high fiber diet) does seem to decrease hsCRP levels, which is likely to decrease subsequent cardiovascular events in those with CAD
    --and, without getting into trying to isolate only one component of diet to see what happens (eg manipulating one micronutrient and giving that as a pill), the real take-home message is that a high vege diet itself, one high in fiber, does seem to have real effects on systemic inflammation
--and, systemic inflammation (at least in the longish term) is associated with several bad health outcomes, not just atherosclerotic disease, but also diabetes, depression, cognitive decline, osteoporosis, and even perhaps COPD.


--so this study adds to the imperative (i think) to reinforce some basic lifestyle issues: exercise and vege/high fiber diets do seem to decrease systemic inflammation. and this is likely in itself to translate into decreased morbidity/mortality.

See: http://gmodestmedblogs.blogspot.com/2018/02/diet-and-depression-in-teens.html , which found that a Western diet was associated with higher BMI at age 14, and higher hsCRP levels, as well as depression and mental health disorders at age 17

geoff

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