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Podcast: Play in new window | Download (Duration: 33:29 — 30.7MB) Subscribe: iTunes | I’m Loren Cordain, founder of The Paleo Diet Movement.
And I’m Shelley Schlender, this is The Paleo Diet Podcast for May 2015.
We’re going to talk about folic acid. Folic acid is an interesting compound. The reason why I say it’s an interesting compound is that it didn’t exist on planet earth until 1947. No humans ever ate folic acid in any form until 1947.
But Loren Cordain, I’ve thought of folic acid as something that you can kind of get through your food. Is this one of those green leafy vegetable or one of those meat nutrients? I thought it was a B vitamin.
That’s what we’ve all been kind of fooled into thinking is that folic acid was something that we could get from food. Folic acid was first synthesized by scientists at Lederle Laboratories in 1947. Here is the structure of folic acid. You can see, folic acid is a completely different compound than naturally occurring folate. Here’s metal folate and here’s folic acid. I’m showing Shelley the chemical structure of these two compounds.
The folic acid looks a little bit like a cul-de-sac where the molecules are here and there and spaced in kind of a boxy sort of circley thing. Whereas the metal folate looks more like a zigzagging street where the houses are kind of along a straight line more.
If we have any chemists out there, folic acid is made up of three compounds. One is called pteridine, the other is PABA, para-aminobenzoic acid, and the other is glutamic acid. These hook together in this configuration make folic acid.
Now that you’re saying that and talking about the Os and the Hs and stuff, even those elements are somewhat different in these two.
That’s really the issue here and the devil is in the detail on science and nutrition. The natural form that we use in our body are called folates and these what are found in green leafy vegetables and organ meats and so forth.
The reason why scientists at Lederle Labs were so interested in folic acid is that it’s a very stable compound. This is not very stable unless it’s in its natural matrix like in a food or a liver.
The methylfolate that occurs naturally is stable in a food, but if you try to take it out and add it back in, it just falls apart.
That’s right. That’s why they didn’t just synthesized folates and give people folates in their native form is because it was very fragile and if you tried to put it in a food or a vitamin or what have you, then it tended not to remain stable.
Let’s back up a little bit here. If this substance, methylfolate, is in food naturally, why did anybody think we needed to add more of a back end? Did somebody take it out of our food?
Biochemists are very much interested in human metabolism. They’re very much interested in determining these pathways in which we metabolize these things. What it turns out is that they actually isolated these pathways way back in that late 40s or early 50s. They isolated these pathways of how folic acid actually works.
In this next diagram that I’m showing Shelley, it’s a diagram that shows how folic acid is handled. Here’s folic acid that comes from a vitamin or a supplement or fortification. Folic acid goes through a number of steps until it becomes the active form of folate which is called tetrahydrofolate. This is where all the action occurs in the cells. This is the compound that is used to make all of these other compounds that are utilized in metabolism.
Early on in the game, scientists that were interested in folic acid found out that if you consumed folic acid, it could be turned into tetrahydrofolate via this mechanism. This is the enzyme, DHFR, which allows that compound to be turned into tetrahydrofolate.
[00:04:00]
Now, as some context, the USDA requires things like Wonder Breads or white breads and other manufactured foods to be supplemented with folic acid.
That’s right. In 1998, the FDA passed legislation which required essentially every man, woman, and child in the United States to ingest this compound, folic acid, for the rest of their lives.
Did they do this because they thought we just didn’t have enough of it in our diets?
No. We’ll get to that in a minute. I just want to point out this pathway and then we’ll talk about why that decision. It was a mandatory, a fortification program, why it became mandatory was everybody in the country eats wheat. Except for celiac patients in 1998 and the paleo diet hadn’t hit the big time then, so basically everybody in the country was eating wheat in 1998. They thought that that’s a good idea to get folic acid into everybody’s blood stream. They weren’t trying to poison us or cause problems …
Yeah, I absolutely do. Not just me, there are entire governments that won’t fortify their food supply with folic acid, because …
Okay, but I like to skip ahead in the chapter just to know what the big picture is. Does the USDA still require us to use folic acid in our foods?
If you eat wheat, if you eat refined cereal grains, you are eating folic acid.
Any flour that’s a wheat flour, it’s been supplemented by law with folic acid?
Let’s just give you a couple of examples here. How about a wrap that you use on your burrito, what’s that made out of?
Folic acid. It’s made of wheat with a little folic acid.
Yeah, and how about the bun on your hot dog?
[00:06:00]
How about the bun on your hamburger? What good American doesn’t eat a hamburger that’s made with folic acid? How about bagels for breakfast? How about sandwiches? How about pasta? How about these gooey doughnut things? How about pizza? How about toast? How about chocolate chip cookies? How about pancakes?
If you wanted to poison the entire country, what would you do? You’d put a compound into a substance that everybody eats every single day.
Now, this was not done by poisoners, this was done by people concerned about human health in the United States who put this folic acid in.
Absolutely. Before we get to that, let me just explain one other factor. Let’s go back to 1947 when the scientists first synthesized folic acid. They watched the way this thing went through metabolism and they found out that it’s stable, so you can put it in food, you can put it in supplements, you can put it in anything and low and behold, it enters into either the liver or the intestinal cells through this pathway and they discovered it could be turned into this active form of folate, tetrahydrofolate.
Everything was good. There was no problems. We found a cheap …
This was before they found out that it kills you.
Well, I’m not going to say … I mean it can potentially could be …
It increases risk. What they didn’t know was this.
You’ve got in your picture here, this happy picture of this causes that. There is a black box. What does it say in the black box?
It says, “Unmetabolized folic acid.” At the time, it was thought that folic acid, until only recently, until only actually the last couple years, it was thought that this was a very efficient process that if you consume folic acid, it all gets converted in the liver and the gut.
It’s a man-made chemical and when it gets consumed, it turns into a helpful, normal chemical, but guess what.
[00:08:00]
Well, that was what the thought was is that there were no adverse effects of this. Now, people are becoming very, very concerned. This enzyme right here, DHFR, this enzyme that converts folic acid to tetrahydrofolate has a very low ability to make this compound. What happens is because this low ability, then the folic acid that is not turned into this overflows and spills into your bloodstream and is unmetabolized.
Now, I don’t want to get too far ahead of the game, but it has now been through epidemiologic studies, animal studies and experimental studies, this looks like is a very, very bad way of going. Now, let’s just do one more look at this diagram. Here’s natural dietary methylfolate. This is what we get in green leafy vegetables and in primarily liver.
You can get this from animal tissues. You can get it from green leafy vegetables. There are plenty of sources of natural methylfolate.
Yeah, and I’m going to show you the highest sources of natural folate and the DRI, the recommended amount is 400 micrograms per day. The highest source of natural folate is spinach.
I have to admit, I don’t like spinach. What else is on the list here?
Caesar salads. Napa cabbage number six. I like Boston lettuce or Bibb lettuce. That’s one of my favorites. That’s number seven in terms of concentrations.
Look at this, parsley is on the list and arugula. I love arugula.
Yeah. You can see there’s all kinds of healthy foods here that people normally eat. There are some that people don’t eat a whole lot like turnip greens or others, but most people, if you look at this list of 18 would say, “Wow, that’s pretty cool.”
You also mentioned that it’s in organ meats.
[00:10:00]
That’s right. If we look at this, this shows the concentration of dietary folate. For those fans that like pâté or goose liver, you can see that goose liver is incredibly high in folate. Chicken liver as well. Beef liver is fairly high but not as high as these bird livers. Fish roe for caviar aficionados. You can see it tends to be kind of high. Then amazingly, crayfish and crab also are fairly decent sources.
I remember one time I sat down with Joe Hibbeln. Joe is a great guy and he lives in Maryland. He took me out one day to a crab shack on Chesapeake Bay and I’ve never been there before. It just look like a divey-looking place. They had picnic tables that were put down on the sand and the only thing they served was steamed crab and beer. That was it.
We must have consumed 30 or 40 pounds and there’s about four of us of this blue crab. We just ate, and ate, and ate, and it was an amazing feast. If you look at blue crab, you can see there’s about 44 micrograms of folate per 100 grams. You can see here that this is only a quarter pound of blue crab meat which is … You can see, look at how calorically light it is. It’s only 87 calories in 100 grams. We easily sit down and eat 1000 grams and you still would only get 870 calories. My point is this crab is a …
It’s a good source. You know what? A lot of times, vitamins are kind of expensive, so why not get your folate from crab?
That’s exactly my point. Now, let’s go back and let’s complete the study and let’s talk about why our food supply, why every man, woman and child in the United States was forced to eat folic acid by an FDA mandate that happened in 1998.
[00:12:00]
Okay, because this is more serious now.
Right. Now, we’re going to get into the serious stuff, is that women who had a low folate status, distinguished between folate and folic acid, women who have a low folate status, it increases the risk of neural tube defects, primarily spina bifida and another neural tube defect called anencephaly.
I knew a marvelous young kid who was in a wheel chair her entire life because she had spina bifida. That’s where the spine at the very end divides into two pieces instead of one. She was paralyzed and she lived until her 20s and that’s when she died.
Yeah. It’s a horribly tragic disease and we’ll talk about how many people and deaths are involved in both spina bifida and anencephaly. That was the idea behind it is that by fortifying a ubiquitous food such as wheat, flour with folic acid, it reduces the incidence of that whole thing.
The problem is it occurs during the first trimester. A lot of women that get pregnant don’t even know that they’re pregnant in the first trimester. That’s the idea behind the population-wide fortification program is that if you’re eating folic acid throughout your live, then it would, in theory, reduce the risk for these neural tube defects.
It also is involved in cardiovascular disease. Folate, not folic acid, but folate helps to eliminate the toxic effects of a compound called homocysteine in our bloodstream. People that have low folate status have high homocysteine. Homocysteine can damage the endothelial cells lining the arteries. Then it was thought, “Well, this is a really good thing. We’re going to reduce the risk for a neural tube defect and secondly, we may even reduce the risk for cardiovascular disease.”
That was the thinking. At the time, in 1998, unfortunately, they didn’t know about those nasty little byproduct here of unmetabolized folic acid. That’s what presents the risk. These are the countries that followed lockstep with the United States. Us adopted or implemented this folic acid fortification program in 1998, so it’s been with us for quite some time. Canada followed step in 1998. Chile in 2000. In Australia in 2009.
Amazingly, most of the European countries didn’t do it. They had concerns about putting a compound into the entire population and not having adequately tested it. This is what we gained in the United States. We have roughly 300 million people in our country and in the US, and the first year before the fortification program. Actually, it was the sixth year period, 1990 to 1996.
The average number of neural tube defects was about 1500. Actually, 1582 per year. The first year following fortification, the neural tube defects dropped to 1337. We put all 300 million people in the US at risk for other diseases and we saved 245 cases of these diseases.
I have complete sympathy for people whose children have neural tube defects. If we could safely do a program like this and save those people, I’d say in a heartbeat, “Do it.” But, if we are putting the rest of the entire population at risk, that’s not fair.
It’s not clear yet, because folic acid is a relatively new substance being wildly used whether there were other damages to developing fetuses because of the folic acid. That isn’t parsed out either.
[00:16:00]
That’s absolutely right and that’s what we’re going to end up this discussion with is that there are now grave concerns that folic acid supplementation may underlie this enormous increase that we’ve seen in autism. In the Journal of the American Medical Association, we’re now starting to see papers in the last year or two that are showing that mechanistically, folic acid can involve the nervous system and we’re seeing epidemiologic studies that show that the increase in autism tends to parallel the increase in this folic acid fortification program.
There are a lot of possibilities for conditions such as autism. It may be a symptom that is at its root many different causes, but you’re saying this might be one of them.
That’s right. It’s not just epidemiologic data, there are pretty strong studies in the highest impact factor journals in the world that have now mechanistically, in other words, they’ve developed the molecular pathway showing how folic acid can actually interfere with the nervous system and potentially cause behavioral issues including autism.
As you’re talking about this, I’m thinking about how you’ve explained that folate is something that’s beneficial to the nervous system.
Folic acid was considered to be something that would be a cheap way to provide the same benefit as folate, but instead, it’s been overdosing people with this compound the body has trouble showing where all of this relates in some way to the nervous system.
[00:18:00]
It is a very unsettling detail and I don’t think anybody deliberately did this. This fortification program was not a plot by the USDA or the Centers for Disease Control to do this. They had a very good therapeutic idea behind it. It just turns out that when we start messing with metabolism that has been fine-tuned by, not just millions, but by hundreds of millions of years, these folate pathways have been around forever.
That’s how the cells are designed. The cells are designed to handle folate, methylfolate and turn it into tetrahydrofolate. They’re not designed to handle folic acid with the hope that it’s going to be turned into tetrahydrofolate. It does, but as I mentioned, there is a side effect if I metabolize folic acid.
Let me just finish up with folic acid fortification. What we’re seeing is that spina bifida is rarely fatal whereas anencephaly is always fetal.
A folate deficiency can lead to these two diseases.
That’s right. There’s other folate deficiencies that I mentioned. Folate deficiency can lead to vascular disease because it tends to allow a compound called homocysteine to build up in the blood stream. It’s also involved in multiple other pathways. Good human health comes from eating folate, not folic acid.
As you’re talking, it’s making me think I’m going to go find some very cheap caviar.
Actually, which one of those leafy greens did you like the best?
I like the arugula and the parsley.
Why don’t you make yourself a big arugula parsley salad tonight and there’s probably recipes right here in this new cookbook that you can use to make it.
In your The Real Paleo Diet Cookbook.
The Real Paleo Diet Cookbook. The folic acid fortification program, if we look at the numbers …
It’s such a sad thing to think about a well-intentioned plan may have done more harm than good.
Yeah. That’s really the issue. Like I said, my heart goes out to all parents and children that have experienced this horrible disease. Anencephaly is almost always fetal at birth or shortly thereafter. Whereas many people as you mentioned with the girlfriend that you had, they can survive with spina bifida.
But it’s a hard disease, so it means …
[00:20:00]
It’s a very hard disease and …
Exactly. If we can prevent that disease, let’s do it. I think that there are better ways that supplementing with folic acid. I’ll show you on the pathway another way that it can be done now. It could be done by the same method we’re using right now, except instead of using folic acid, we could use another compound that we could fortify our bread with and it wouldn’t cause this problem if that’s how we want to do it.
My point is is that the total number of lives that would have been save, roughly in the year after we started the fortification program, it would have been about ’83. Unfortunately, we have population wide increases in breast, colon and prostate cancer that have been linked to high folic acid status. Here’s just the list of 15.
You’ve now mentioned autism as a possibility and also now breast, colon and prostate cancers and heart disease all may have some increased risk with folic acid fortification.
People have been following this for probably even the fortification program began in 1998, but after it began, many research groups around the world have really focused in on it. The problem is, as I mentioned earlier, is this unmetabolized folic acid. What it tends to do is when we get folic acid in the bloodstream, it looks like it interferes with this normal pathway.
Here’s how you can see natural dietary methylfolate enters the pathway and is eventually turned into tetrahydrofolate. It looks like this unmetabolized folic acid in the bloodstream interferes with this entire process. Folate metabolism then is disturbed. This then is thought to be one of the reasons behind why folic acid causes so many problems particularly, as you mentioned, the autism and behavioral problems is because we know that normal folic acid metabolism must occur in nervous system to have normal behavioral outcomes.
Even more disturbing is the notion that folic acid can cause what’s called a hypermethylation reaction in cancer cells. This then is the thought how in animal models of cancer. We can induce cancer in animal models by giving them folic acid.
Hypermethylation basically means that you unwrap DNA instructions and switch them on.
That’s right. This is the thought then of how this compound may be associated with all these epidemiologic … Actually, there are experimental randomized controlled trials showing folic acid is responsible. Here’s a 2010 meta-analysis that showed that folic acid is associated with population-wide increase for prostate cancer.
Here’s even a more powerful study. This is what’s called a randomized controlled trial and this holds more weight in the scientific community than descriptive or population-wide studies. What they did here is they gave 600 men folic acid and they supplemented them for 11 years in the supplemented group. About 10% of them develop prostate cancer, whereas in the placebo group, only about 3% develop prostate cancer.
That was in the Journal of the National Cancer Institute in 2009.
Right. Those kinds of studies are very disturbing that you have a 200% increase in prostate cancer in the supplemented group. Here’s another one. This one I believe came out of … No, this one came out in the United States. Here is a study of 10,000 men and women carried out for a 10 year period.
This was in the Journal of the American Medical Association in 2007.
[00:24:00]
Right. These kind of studies are coming out in topnotch, high impact factor journals that normally don’t take junk science or poorly controlled studies. It showed that the risk of three or more adenomas, these are cancers, non-colorectal cancer. The risk for all cancers were increased in the supplemented group.
This is an interesting one. It came out of Norway, published in JAMA 2009. Here’s a quote directly from the author, “Treatment with folic acid, plus vitamin B12 was associated with increased cancer outcomes, all-cause mortality in patients with heart disease in Norway where there is no folic acid fortification of foods.”
The idea here with this study was, again, the same issue about homocysteine. The thought is if we can increase folate concentrations in the bloodstream, we can lower homocysteine and reduce the risk of heart disease. Actually, it turned out entirely the opposite. It didn’t reduce the risk for heart disease. It increased all-cause mortality and it increased cancer.
Did it increased the homocysteine or did it decreased it?
I don’t know off the top of my head. I’d have to go back and look at that, but that one, it’s published in JAMA 2009.
You know what, even more compelling than whether increased or decreased homocysteine is how many people died. That’s kind of the bottom line, isn’t it?
That’s absolutely the bottom line. It is a disturbing blunder. To my way of thinking, it’s one of the worst disasters in public health that we’ve seen in a long time is to increase the risk for the entire population to save 87 people which is a noble thing to do. It’s a very noble thing, but there’s an easy way out Shelley and let me show you the easy way out that we could reverse this whole problem.
Meaning that you could reduce the number of kids who get these neural tube defects and you could protect the rest of the population too.
[00:26:00]
That’s right. Here’s the pathway for natural dietary folate. Here’s what we get in our leafy greens and our liver and our fish roe and crabs and so forth, and you can see that the very first step here is to turn this thing into five methyltetrahydrofolate. Then you can see, this compound then is turned into tetrahydrofolate which is the active form.
This is a little more expensive to make and it’s not quite as stable as folic acid, but we can make this compound and we could fortify our cereal grains with 5-methyltetrahydrofolate and we would not have this problem.
Meaning that we would not have the excess unmetabolized folic acid.
That would be the solution if we still want to go on with the fortification program. I agree, many women who become pregnant in the first trimester are unaware that they’re pregnant and the damage has already been done if they’ve been eating the typical American junk food diet, but I can honestly tell you that if you eat in this manner …
You’re pointing to The Real Paleo Diet Cookbook, your new cookbook.
If you eat in this matter, it’s almost impossible to become folate deficient. The reason being, I and other people that encouraged this paleo diet concept, we encourage people to eat these kind of foods on a daily basis.
All these leafy green vegetables.
Spinach, endive, romaine lettuce, Napa cabbage, Boston lettuce, parsley, arugula, chives.
Liver is on the menu. The highest concentration, goose liver is one, chicken liver is two. If you like giblets … I know many people feed those to their pets, but they can be sautéed up and I’m sure with some of the recipes in the new book, you can make a delicious meal out of those crabs and crayfish. It also tend to be a pretty good source.
The reason that they’re a good source is that they’re so low in calories that we can eat a ton of these. You can eat a quarter pound of crab and you’re not even started.
Loren Cordain, if somebody has been supplemented either inadvertently through just eating wheats and breads or by using folic acid supplements, do these things stick around in the body forever and ever or does the body get them out?
Unmetabolized folic acid has a pretty rapid half-life, but the problem is we eat it every single day at every single meal.
If somebody is eating the regular American diet full of grains.
If you eat bread, you’re getting this. You get a dose for breakfast, a dose for lunch and a dose for dinner. Then in your snacks, you’re probably getting a dose of it as well.
Somebody who’s a celiac who eats gluten-free bread, is that probably supplemented with folic acid too?
I think it’s only been wheat flour that is supplemented, so if you’re eating other grains, to my knowledge, they haven’t been supplemented with folic acid. One of the other major sources is multivitamins. If you take a multivitamin, even at simple like one a day, they give you the DRI and they usually give you a little bit more. If you take the higher end, you get anywhere 800 to 1200 because more is better, right?
If you take a vitamin, look and you’re likely to see that folic acid is part of a multivitamin right now.
I have an anecdotal story to tell and I’m not going to name a name, but one of my good friends from the health community, he was a young man and has written many books on health. He was very well known in the United States. He put on conferences and before paleo ever got big, he invited me to come speak with some of his conferences. I enjoyed him. He’s a wonderful person. He was a credible piano player, a musician. He just had all kinds of talents.
His interest was in health and wellbeing. He was kind of a vitamin supplement type guy that if a little bit is good, more must be better. He wrote a book on folic acid. He thought that we weren’t getting enough folic acid. In his life time, I understood after he died that he was supplementing to the tune of ridiculous amounts of folic acid. The DRI is 400 micrograms. Hey may have been supplementing to the tune of 10 or 20 times that daily for years and years. I think he’s five to eight years younger than I was.
No. He died of colon cancer in his late 40s.
Who knows, but I’ve often thought about that. I wish we would have had that information.
About folic acid a decade ago, because you can see these studies that I’ve shown you, they date to the last couple of years. The autism studies, when I first wrote my book, The Paleo Answer, I wrote in 2012, there wasn’t as much in the literature now, but for your readers that know PubMed or MEDLINE, they can go online and type in folic acid and autism. Up and becoming in the Journal of the American Medical Association 2013, is a study that outlines a lot of the background on how and why folic acid may predispose our children to autism.
Grains are very low sources of folate. I showed you the highest sources here and there’s no way in the world. You could eat five pounds of whole wheat and you still wouldn’t got in a quarter pound of spinach or romaine lettuce.
[00:32:00]
Eat your vegetables. Eat those leafy green vegetables.
Yeah. The message is eat those leafy greens and try to replace cereal grains with real living fruits and veggies and real meat.
Organic chicken liver. That’s the way to go.
I actually like chicken liver. Some people don’t, but you can cook it up with onions and other things and make it taste pretty good.
That’s all for this edition of The Paleo Diet Podcast.
Our theme music is by Chapman Stick soloist Bob Culbertson.
Visit my website, thepaleodiet.com for past episodes and for hot links to my research, studies, books and latest writings. For questions or comments, the place to go is thepaleodiet.com.
For The Paleo Diet Podcast, I’m Shelley Schlender.
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