My All-Day Heart Food Green Smoothie: 4 Cups of Kale, 1 Cup of Carrots, 1 1/4 Cup of Frozen Berries, 1 Orange, 1 Kiwi. A Big 9p21 Gene Turn-Off!
"A diet high in fruits and vegetables appears to mitigate the genetic risk of a heart attack.
We observed that the effect of a high-risk genotype (variations of chromosome 9p21) can be mitigated by consuming a diet high in fruits and vegetables.
Our results support the public health recommendation to consume more than five servings of fruits or vegetables as a way to promote good health."
Sonia Anand, is the study's joint principal investigator, a researcher at the Population Health Research Institute and a professor of Medicine and Epidemiology at the Michael G. DeGroote School of Medicine at McMaster University. "The Effect of Chromosome 9p21 Variants on Cardiovascular Disease May Be Modified by Dietary Intake: Evidence from a Case/Control and a Prospective Study," PLoS Medicine, published ahead-of-print on October 11, 2011.
If you received this post via email, click here to get to the web version with all the links.
For almost three weeks I barely looked at my computer, read a medical journal article, listened to NPR, watched television, or read a newspaper. But, somehow, even I didn't miss this exciting Canadian diet/gene article!
I was busy enjoying the deliciousness of caring for a sweet toddler, while my son & daughter-in-law were hard at work bringing a gorgeous healthy baby girl into the world. I'd say 56 hours of labor was hard work!
And what more exciting news is there than a new baby?
I was doing the most important work I could think of at the time--playing & snuggling with my grandkids, reading picture books, going to the playground, coloring, preparing meals, grocery shopping, negotiating with a 2 year-old, doing lots of laundry, changing diapers, washing dishes, and best of all--giving "Beginning of Life Care" to my family. Absolutely the best! Stay tuned for more on that story...
Stuck with Bad Genes? Think Again! Fix Them with Vegetables & Fruit? What??
I hear it all the time.
Cardiovascular disease is all about the genes you're dealt. And there's nothing you can do to change that hand. So why bother changing your diet? Bring on the cheeseburgers & fries. Enjoy life.
Well, it's time to rethink that erroneous line of reasoning!
Dr. Sonia Anand & Dr. Ron Do were the principal investigators of a recently published study in PLoS Medicine that has now put the KIBOSH on the "I'm stuck with bad genes" fairy tale!
I'm just saying....If you're going to skip your fruits & vegetables--you're making a big mistake.
Their study is the largest gene-diet interaction study ever conducted, and it encompassed multi-ethnic & racial groups--Europeans, South Asians, Chinese, Latin Americans, & Arabs. You heard right--the 9p21 gene exists in all racial & ethnic groups. It's not just a Caucasian thing.
What's Up with This 9p21 Chromosome? Explaining the Back Story - Its Inflammation Connection
The 9p21 chromosome is the most robust gene ever associated with heart disease.
Since 2007 scientists from all over the world have identified variations of this gene that are linked to cardiovascular disease & heart attacks. This is a proven unquestionable finding. If you have one or two copies of this gene--your risk of heart disease goes up. How much? Who's stuck with this gene? More on that later...
Researchers already knew that this gene was bad news for heart disease, but it was only recently that they figured out how & why it caused so much damage!
The missing puzzle piece? The 9p21 gene is an inflammation driver. It does its dirty work by increasing inflammation in the endothelial cells that line blood vessels! This is a huge AHA discovery!
If you carry this gene you are at a higher risk of coronary & arterial diseases because it makes you more susceptible to inflammation than non-carriers.
Turns out, Dr. Kelly A. Frazer & her colleagues at the University of California at San Diego used some new-fangled three-dimensional DNA selection & ligation (DSL) technology to determine exactly how this gene increases arterial inflammation--which helps to explain why having a copy or two of this gene increases one's risk of cardiovascular diseases. See: Harismendy, O., Notani, D., Song, X. et al. "9p21 DNA variants associated with Coronary Artery Disease Impair Interferon-{:gamma;} signaling response," Nature 2011; 47-264-268 Click here for the article.
According to Dr. Eric Topol, one of the study's co-authors:
"This connects the dots for the 9p21 markers with multiple vascular phenotypes---coronary artery disease, myocardial infarction, abdominal aortic aneurysm, and intracranial aneurysm---to inflammation.
It explains why 9p21 affects not just risk of coronary artery disease, but also aneurysms--because inflammation, as well as causing atherosclerosis, can weaken artery walls."
And according to Dr. Kelly Frazer:
"[I]t opens up ways of thinking about people who have this particular [9p21] variant as a susceptibility--you may want to monitor their inflammation more than other aspects--eg, cholesterol--because when people think about coronary artery disease, they tend to always focus on cholesterol." (for inflammation, think about the C-Reactive Protein (CRP) Test)
My comment: If the 9p21 gene increases vascular inflammation, consider what other environmental/lifestyle factors further increase inflammation & cardiovascular disease independent of genes.
A diet high in omega-6 oils and the long-chain omega-6s found in grain-fed meat, saturated fats, trans fats, too little sleep, too little exercise, refined grains, too little fiber, too much sugar, abdominal belly fat, and a diet low in fruits & vegetables? Are you beginning to connect even more dots? Does this help to explain why a plant-based no-added oil diet is protective against cardiovascular disease?
Read more in:
Why Vegetables & Fruit Can Mitigate the Risk of the "Heart Disease" Gene
Once you know that having the 9p21 gene makes one more susceptible to inflammation, you can better understand why people who have this gene might decrease their risk of heart disease by eating lots of inflammation-inhibiting fruits & vegetables. You know--the "anti-oxidant effect".
But, wait a minute! The McGill/McMaster Diet-Gene-Heart Disease Interaction Study was going on long before anyone knew that the 9p21 gene was responsible for vascular inflammation--which makes the study's results even more exciting.
How the McGill/McMaster Diet-Gene Interaction Study was Set Up
The Canadian researchers looked at two large international study groups totaling more than 27,000 people--from both the INTERHEART Study & the FINRISK Study--and identified which people had copies of any of four varieties of the 9p21 gene.
They compared the eating habits of those who had the gene with those who did not. And then they looked at who had a myocardial infarction--and who did not--and compared that with their eating habits & their genes.
The result: The people in the study who ate a "Prudent Diet" that was high in raw vegetables & fruits lowered their risk of heart attack even though they had the high risk gene.
Ira Flatow Interviews Dr. Sonia Anand of the Canadian Heart Disease-Diet-Gene Interaction Study
I'm a huge fan of NPR's Ira Flatow, and his Science Friday radio interviews with cutting-edge scientists & researchers.
Listening to his recent interview with Dr. Sonia Anand helped me to better understand the 9p21 gene study--and answered a lot of practical questions that I had.
How many of us have this gene? How common is it? How much can diet affect this gene? How many fruits & vegetables do you need to eat to silence this gene?
Click here to listen to the interview yourself.
Here's what Ira Flatow asked Dr. Anand:
Tell us more about the 9p21 gene?
Having this gene increases your risk of heart attack. It was discovered in 2007 & since then, many investigators have replicated this finding--so we really understand the effects of this gene quite well.
If you have one copy of the bad gene, or 2 copies of it, you have a significantly increased risk of a heart attack.
People who ate a healthy diet, even with an increased risk from the gene, lowered their risk. Please explain.
First we confirmed that the 9p21 gene was a risk factor, & then we looked at whether a diet high in raw fruits & vegetables would protect someone with the gene, from heart disease. It turned out that it did.
Then we looked at groups of people in different combinations, dividing people up by their gene status, and their dietary habits. We found out that if you had the "bad gene" & consumed a "bad diet" that was low in raw fruits & vegetables, your risk of a heart attack was increased by 30%.
But, if you had the "bad gene", and consumed a "good diet", high in raw vegetables & fruits--your risk of a heart attack was no different than those who did not have the "bad gene". So, the risk was brought down back to 1. (Note: Other lifestyle factors also affect one's risk of heart disease, e.g. physical activity, smoking, obesity, alcohol consumption, etc, regardless of one's genes. This study looked only at how diet can affect those with a genetic risk of heart disease, as compared to those without a genetic risk. In most common diseases, both lifestyle & genes play a role. The 9p21 gene ups the risk of myocardial infarction by 1/5 over those who don't carry the gene.)
Do fruits & vegetables have some mechanism to turn the gene off, or affect how it's working?
From this broad population observation, we believe that it's true--there are good properties within the raw fruits & vegetables that actually silence or turn off the gene.
We don't understand how, and I believe that future studies should be focused in this area to understand at the level of the DNA what actually happens when people are consuming high quantities of fruits & vegetables.
Could you tell from the study which fruits and vegetables were the best at silencing the gene?
We conducted the first study in 5 different ethnic groups (the INTERHEART Study included Europeans, South Asians, Chinese, Latin Americans, & Arabs) and the main driver of the protective effect of this diet appeared to be among people who consumed RAW vegetables & fruits.
We then wanted to test our observation in a second study--and looked at the FINRISK Study from Finland. They measured diet slightly differently than in the INTERHEART Study. We found in that study, that any vegetable, both raw & cooked--or fruit or fresh or frozen berries seemed to have a protective effect. So, I think that any of those--raw or cooked vegetables, fresh or frozen fruit or berries--are likely protective. My comment: Should we consider the ORAC Index or Dr. Joel Fuhrman's ANDI -Aggregate Nutrient Density index?
How many people have the 9p21 gene? What percentage of the population has 1 or 2 copies of these genes?
50% of the population carries one copy of the "bad gene".
20-25% of the population carries two copies of the gene. So it's actually quite a common gene.
*To clarify these figures:
"9p21 occurs in 75% of the population except for African Americans and is associated with a 25% increased risk for CAD with 1 copy and a 50% increased risk with 2 copies. Perhaps the most remarkable finding is that 9p21 is independent of all known risk factors, indicating there are factors contributing to the pathogenesis of CAD that are yet unknown. 9p21 in individuals with premature CAD is associated with a 1-fold increase in risk, similar to that of smoking and cholesterol."Clinical Chemistry 2011 Oct 20. [Epub ahead of print] Roberts, R, Stewart, AF, "9p21 and the Genetic Revolution for Coronary Artery Disease." Click here for article
Does diet affect the risk of heart disease equally--or does the risk go down equally if you have both genes?
If you have two copies of the "bad gene" & you are consuming a "bad diet"--your relative risk of a heart attack is increased 2 times, or 200%
If you have only 1 copy of the gene, and you're consuming a "bad diet", your risk of a heart attack increases about 60%.
So, two copies of the bad gene is worse than one copy--and any copy of the "bad gene" is worse than not having it at all.
Is there any way to know if you have a copy of the gene?
The genetic test is not widely available. Physicians don't use it in their risk prediction.
There are some private companies that people can send their saliva or a blood sample to--and pay out-of-pocket to get this testing. But, I think that outside of the research context, our findings should encourage all people to increase their fruit & vegetable consumption, because we know that high consumption of fruits & vegetables is not only protective against heart disease, it's also protective against stroke & some types of cancer.
In your study, how many fruits & vegetables did people eat during the day?
To be classified as a "high consumer", you had to be consuming fruits, vegetables, & berries in multiple servings per day--at least two was average--but likely, if we put our findings together with the public health recommendations, it would be eating at least five to six servings a day. That's the best advice! And a serving is the amount you can hold in the palm of your hand.
So, if you have a couple of servings a day, that would be protective?
That's consistent with our study, and we have observed that that amount of fruit & vegetable consumption can silence this "bad gene".
Can you get even "better silencing" if you eat more fruits & vegetables?
Well, we don't know of an upper limit--so we don't think there's a point where you can consume too much, or have adverse consequences. Other studies have demonstrated that the higher number of servings per day, the better your health. At least two per day--but likely more is better!
Do you think this study & the effects of diet on this gene explains why people who eat a healthier diet are healthier?
Well, it's one of the first clues between this observation of fruits & vegetables on health--and the potential interactions between a good diet & genes.
I think it's important because we often think that if something runs in our family, well, it's in our genes. There's nothing we can do to change it--but now we have a hint that perhaps we can silence our genes & change our family history by embracing a healthy lifestyle.
Were you able to find out what role exercise might have with the healthier diet?
Yes! In our study we looked at various factors that may alter the expression of this gene, and we really came up big with this signal from diet!
We didn't find that there are other interactions either positive or negative with other health behaviors, with respect to modifying this gene. But, I will add that whenever you divide the study population many many times, in difference subgroups, your results become less reliable, because you don't have as many people. That said, this study doesn't rule out the fact that exercise may turn off or enhance protective genes, but we can definitely see the observations of the protective effect of diet on the 9p21 gene.
Where will your research go from here?
In terms of research & next studies, I see three different lines of upcoming research.
- First is at the basic science level--trying to understand how this type of diet may alter gene expression.
- Secondly, we hope to replicate, replicate, replicate our observations in many other studies. Versus heart attack. Versus stroke. And the more we see this observation repeated, the more believable it will be.
- The third line of research, which is pretty exciting, is trying to understand if an individual's knowledge of their genetic risk will actually alter their health behaviors. Will this informations cause more people to embrace a healthy lifestyle & diet, than if they didn't have this information?
What Does Dr. Eric Topol Think of the Canadian Diet-Gene Study?
Topol is one of the country's leading experts in cardiovascular genomics. He's a professor of translational genomics at The Scripps Research Institute, and Director of the Scripps Translational Science Institute in La Jolla, California.
It was his recent research that identified the 9p21 gene's inflammation connection.
Here's what Topol had to say about the Canadian study:
"The study findings suggest that lifestyle does matter, no matter what your genes have dealt you.
This suggests you may be able to do something about it [bad genes] if you follow a prudent diet that is rich in fruits and vegetables.
I think this is a very sound report. It's really one of the first solid evidence of this whole field of nutrigenomics. (the way genes interact with nutrients)
The researchers found a dose response. The worse the diet, the higher the risk of heart attack. The better the diet, the lower the risk."
It goes without saying, that probably none of this comes as a big surprise to anyone who has been reading this blog for awhile.
But, it helps to confirm & and perhaps explain how a plant-based diet that's high in nutrient-dense vegetables & fruit can prevent and reverse heart disease--in Dr. Caldwell Esselstyn's patients--and for those who have duplicated his diet on their own!
I'd love to hear your reactions to this study!
Amazing! Thank you for yet again sharing such important information. Cheers
Posted by: Ginger | October 22, 2011 at 06:16 PM
Congratulations on the birth of your granddaughter. Very exciting!!
I'm pretty sure that I have the 9p21 gene. It's good to have proof that diet trumps genes. Thanks for the info.
Posted by: Penny | October 22, 2011 at 07:16 PM
Congratulations on your expanding family.
Perhaps the most striking aspect of this is that 50% of us have the 9p21 gene. Stated another way, even if this doesn't apply to you, it applies to your children, parents, friends. Moreover, if the link is inflammation, chances are there are parallel situations where by other genes which cause disease via inflammation can be turned off via diet and exercise.
Given the incredible technological acceleration in gene sequencing and bioinformatic technology in the past decade, I suspect we are less than two decades away from genome sequencing as a common medical approach. As such, we'll all know how many copies we have of all of these genes in the near future.
Posted by: Chris G. | October 23, 2011 at 04:18 AM
Thank you Ginger, Penny, & Chris G.
Chris,
Actually, 75% of us have either 1 or 2 copies of 9P21. The quote in my post was a little ambiguous, so I did a little checking to clarify it.
This comes from a "hot-off-the-press" ahead of print article in:
Clin Chem. 2011 Oct 20. [Epub ahead of print]
Roberts, R, Stewart, AF, "9p21 and the Genetic Revolution for Coronary Artery Disease"
"9p21 occurs in 75% of the population except for African Americans and is associated with a 25% increased risk for CAD with 1 copy and a 50% increased risk with 2 copies. Perhaps the most remarkable finding is that 9p21 is independent of all known risk factors, indicating there are factors contributing to the pathogenesis of CAD that are yet unknown. 9p21 in individuals with premature CAD is associated with a 1-fold increase in risk, similar to that of smoking and cholesterol."
Posted by: The Healthy Librarian | October 23, 2011 at 12:00 PM
I've purchased a Vitamix for my office and our entire staff has a raw veggie/fruit smoothie every day for exactly this and other positive health reasons. Sure beats the usual coffee and non-dairy creamer service offered in most offices. It's a little more work, but so worth it.
Thanks for keeping our eye on the important reasons WHY we should expend the effort and eat tons of fresh veggies and fruits instead of the usual modern empty/processed diet that's so ubiquitous.
And congrats on that grandbaby and time w/ the grandtoddler!
Posted by: Cynthia Bailey MD, Dermatologist | October 23, 2011 at 12:17 PM
Great work! I'm so excited that genetic research is backing up what has been observed for a long time. Lifestyle is far more important than genes. It's long been my belief that we ALL have heart disease in our genes, this study helps confirm that. But best of all, it means you don't have to be a helpless victim.
Posted by: vegpedlr | October 23, 2011 at 01:03 PM
Deb,
First of all...Congrats on the new little baby! Best of everything to you and the family! It sounds like nothing but fun to me. Having had a 72 hour labor from hell, I can totally relate! In the end, the BEST kid popped out.
So nice to have you back online! I had my yearly physical today with my wonderful doctor. She listens to all my rantings and ravings I read about here and she's interested in all of them. In light of Tara's WELL column today, we decided to put off the mammogram, and we even talked about endothelial cells! We also spoke about my plant-strong diet, Dr. E, and she's amazed that I'm sticking to it and doing so well. This new piece of research only fuels my fire more. It's both exciting and ground-breaking. Interesting to read about 9P21 having a hand in aneurysms...my dad not only had heart disease, but eventually also had dangerous surgery for his abdominal aneurysm-which eventually did him in. I didn't even connect those dots! Wow.
I'm so happy to be reading this. It's a great piece, Deb.
Mazel Tov...Gael
Posted by: Gael in Vermont | October 24, 2011 at 05:02 PM
Dr. Bailey,
I hope your staff knows how lucky they are! As always, thank you so much for all your positive & generous feedback. It's so appreciated.
Vegpedlr,
I agree 100% With 75% of us carrying this gene--turns out your suspicions were right on the mark.
Gael,
Thanks of the congrats! 72 hours? OMG--I knew you were a strong woman, but that's ridiculous. I agree with your surprise about the aneurysms (me too!) --interesting stuff. Your doc sounds terrific & unusual (lucky you!)--I haven't had a chance to read the entire Well column on mammograms-just the first paragraph--and already I was wondering the same thing--less frequent mammograms. A lot to consider. I know you're a big fan of Dr. H. Gilbert Welch's as well. Almost a hometown boy.
Posted by: The Healthy Librarian | October 25, 2011 at 05:31 AM