 Christopher Gardner I've known him intimately for 52 years. I'm as stunned as he is that he's on the podium today because originally he was a philosophy major undergrad and all he really wanted to do was have a vegetarian restaurant. Somehow he ended up with a PhD in nutrition science and SPRC gave him a shot and he took it and he's still here and he's recruited 1,100 people and fed them and bled them. He's given them garlic and soy and ginkgo and vegetarian diets and the Atkins diet and now he'll share some of those insights with you. Thank you very much Dr. Gardner. It's a pleasure to be here. Alright so a few insights on tailoring dietary approaches for weight loss. I think you'll get a kick out of some of this. I don't know if you've seen all this that we've been doing. So I was actually never really interested in weight loss. I wanted to be doctor phytochemical. That was my goal in life for a while until everybody kept asking me if I thought Atkins or Zone or Ornish were better and I decided to jump into this foray and try to help people sort through the fiction versus non-fiction diet books. I don't know how successful we've been. There's a long way to go but we did do a large study that's been cited many times and we picked a spectrum of popular weight loss diet books. One of them in the middle is actually a health professionals approach, the learn manual. It's got a nice publication in JAMA which caught me a brief moment of fame that introduced me to some really interesting people. I'm going to share the main result with you which is the least interesting part of this whole story. So the main result after 12 months among 311 women among whom 80% came back 12 months later was that the Atkins group fared a little better. It was only statistically significant versus the Zone group and the weight was coming back on faster than the other groups so maybe that would have gone away and I don't really want to hang my hat on this other than to say yeah on average they got some modest, very modest weight loss and with a modest weight loss they actually had a lot of improvements in triglyceride, blood pressure, things like that but I've shown this slide many times. It was never in the paper and I can't tell you how many people have asked me for this slide because this is the 300 women in the study each one represented by a single bar. This is their 12 month weight response and so instead of capturing the average this captures the heterogeneity. So even though there were some modest differences between groups or among groups, I think what's most striking is in all four of the diet groups with very different sets of recommendations, some women lost 20, 25, and 30 kilos and within those same groups some women gained 5 and 10 kilos and so really I think what's much more striking than the very modest differences among groups is that within every one of these four diet groups there's a 30 kilo range of weight change over 12 months and it seems like that's much more interesting than these modest among group differences and so I've seen a couple other folks report the same thing. Here's Bill Yancey decided to plot these graphs out. The red line is obviously the average and then all the individual very narrow black lines are the individual responses which is just this huge enormous variation and in another study that compared some popular weight loss books the average is the line that goes below zero but really look at that amazingly different response of the people assigned to these diets which is what this graph represents. So it's really not true that everybody who's overweight or obese are the same as you've heard again and again from some of our speakers today. In fact it really looks a lot more like this and maybe this is part of the puzzle that we need to go after. Are there ways to target people? Can we use the TGHDL ratio or some other simple method? So looking at this very crudely and Jerry don't get mad, I mean this is all I had. I had fasting levels I'd love to have your SSPG but we didn't. I'm going to show you some of our data but first I'll show you what got me started on that. I thought three different papers, good investigators, good journals who found one way or another to get a hint at insulin resistance or insulin sensitivity and it's amazing how it varies. I'm sure Jerry will agree. Some did 30 minutes into an oral glucose tolerance test splitting at the median of the insulin level. Some did a fasting level where they broke them into less than 10, greater than 15 and got rid of the group in the middle. But however it was, they found that the insulin resistant, the more insulin resistant like folks were different in weight loss on low carb versus low fat diets which you wouldn't see if you lumped everyone together. So I went back to our data and I said okay who was the lowest fat diet and who was the lowest carb diet? So these were our two extremes the Ornish and Atkins group and that's the overall 12 month range of differences that we got but we went back and took simple insulin turtiles and Jerry I did this for TG over HDLC it was the same. I did it for TG turtiles didn't really matter. So what we've got in the top two lines are the most insulin sensitive turtile by virtue of a fasting insulin less than 7 and the bottom two are the most insulin resistant. The fasting insulin is greater than 10 and so really what you see here is despite our main finding that there was a modest difference in the insulin sensitive group they lost the same amount of weight even if they're on Atkins or Ornish didn't really make any difference and the one group that really stuck out was the crudely measured more insulin resistant people assigned to Ornish that was the biggest difference relative to those who are insulin resistant who are assigned to Atkins. So that's an enormous I mean they almost lost no weight at all if they went on the Ornish diet. I have to say they did not follow the Ornish diet very well I'm not going to show these slides but shooting for Ornish and falling short puts you smack dab in the middle of the national guidelines for a 30% fat diet and so this is the 30% fat diet that we've been recommending for decades and it looks like a third of the population this might be exactly the wrong diet especially as our population gets heavier and heavier and more and more insulin resistant. So to follow up on that this is going to seem like a sidetrack but bear with me. One of our postdocs Sophia Alhassan looked at our data we have four diet groups one of them doesn't have a good metric for adherence but for the three popular diet books we had adherence measures and this is going to be stunning I know several of you are going to fall out of your seat this slide says if you followed the diet you were assigned to you lost weight if you didn't follow the diet you were assigned to you did not lose weight got that published can you imagine that we got that published but really what crosses your mind when you think adherence or lack of adherence when you hear lack of adherence do you think weak will not ready things going on in your life so we follow that up a little more especially in terms of this insulin resistant versus more insulin sensitive group and this is what Arianna McLean has been working on so sorry Arianna to steal your results they're almost published she revised and resubmitted them and they'll probably be accepted any day now she has a different graphic so I'm not reproducing her graphic but picture this this is the 12 month change in carbohydrate and fat intake in just the Atkins group and just two of three turtles the lowest in the highest turtle of fasting insulin so this is the crude measure the proxy for insulin resistance it doesn't really matter at two months they really lowered their carb and raise their fat and then we have some recidivism but at at the end of 12 months they're still quite a bit different than they were at baseline so make sense they all got the same advice they didn't know if they were insulin resistant or insulin sensitive so wouldn't that same thing happen if you were assigned to Ornish but apparently not apparently not even knowing if you were insulin resistant or insulin sensitive led you if you were insulin resistant to not adhere to the diet that you were assigned to so by 12 months they don't have their diet isn't any different than baseline so it's fascinating we've been telling all these people to go on a low fat diet which they have a hard time adhering to and are losing weight so could we quickly clinically identify these people yes Jerry just told you how you can do the SSPG if you have lots of time and money or you can do a fasting measure of TG over HDLC and you may be able to identify people who would do better on a low carb high fat diet which is completely contrary to our public health recommendations for so long now I don't have time to show these results because I'm going to try to stick to my 10 minutes we have some really interesting genotype data where a group from Massachusetts came up with this three snip multi locus genotype and genotype our study population retroactively and looked at their response in weight loss to low carb versus low fat diets and it worked they could actually predict who would lose more weight based on this multi locus genotype and we probably got an R01 funded we're in the 10th percentile the project officer has been asking for all my just in time materials Abby and John Yonidis are and Manisha are collaborating on this with me and we'd be anxious to hand our blood samples over to the immune group for immune profiling or give Tracy some fat cells so that she can look at some adipocyte differentiation so that's coming and and later in the day if anybody has an ideas we haven't started this it'll be 300 or 400 people we're going to genotype them we're going to randomize them to low carbon low fat they're going to lose some weight some will be more insulin resistant to start with some will get better after they lose weight so it might be some fun follow-up here and lastly I'm just going to whiz past this one we did a study that didn't work very well with sleep we recruited insomniacs who are overweight and didn't tell them this was the purpose of the study but we randomized them to cognitive behavioral therapy so we'd fixed their insomnia before they tried to work in their diets in a matter of time so I'm not going to show that one and I will just say that I'll do a shameless self promotion a month from today in the same room will hold food summit to well we'll get beyond diet as nutrients and look at diet and that economic legal educational or science perspectives that drive people's motivation as much as Tom is just speaking about thanks the proceeding program is copyrighted by the board of trustees of the Leland Stanford junior university please visit us at med.stanford.edu