Molecular Level Answers

This site is old!

Said the author of this site with some dismay.

I'm doing some spring cleaning and integration of my articles on my new author site, here.

An updated chapter from Herbs Demystified: Catnip!

 

 

About a year ago I started updating a randomly selected chapter from my book. I thought, I'll just start with the plants that grow locally, to narrow it down! Well, just one chapter took over a month of work. Exhausted, and now busily working on the novelization of our science fiction comedy movie, The Emissary, this project remains on the back burner for now. But it is shame for this doc to sit on my desktop unread, I realized. It feels wrong to work really hard on a project and not share it, so here it is!

  Download Catnip-update

 

The Real Reason Why Formaldehyde is Toxic--and how to avoid it

 

Formaldehyde is where you least expect it.

If you ask most people, their first experience with formaldehyde arose in high school biology. Perhaps you recall biological specimens ominously afloat in jars of stinky liquid. (Formaldehyde is actually a gas, not a liquid, but because gasses are so inconvenient to deal with what with their flying around a room uncooperatively, formaldehyde is usually dissolved in water to make it more compliant—and if it is around 10% to 30% this mixture is then called formalin.) Or if you are like me, you associate formaldehyde with the smell of embalming fluid if you have spent any time hanging around cadavers (sometimes I teach anatomy).

 

Now what surprised me in researching formaldehyde was just how many modern products contain or release it, from cosmetics to building materials and even some common, chemically-treated forms of cotton, wool, and silk—what I'd presumed was "natural" fabric. The word "formaldehyde" does not appear in the ingredients list of any cosmetic that I am aware of, and I'd be startled to find it there. However, many lotions, hair products, deodorants, and other cosmetics contain preservative molecules that react to become formaldehyde, known as formaldehyde releasers. I have a list of these releasers below. (You could always copy the list to bring it to the store with you the next time you go shopping, to squint endlessly at ingredient lists to find them, as I now do. Think of it as a sort of un-treasure hunt.)

 

What you don't know can hurt you.

Exposing yourself and your family to formaldehyde in apparently benign consumer products is worth thinking about. This is because of excellent, what scientists like to call rigorous, evidence that formaldehyde causes, at best, contact dermatitis, allergic reactions, and rashes, and at worst, cancers like leukemia. You can bore yourself, as I have, reading lots of published, peer-reviewed, epidemiological and laboratory studies in reputable science journals to confirm there's sound evidence for this. Now, I don't think we need to panic, but it does make sense to educate ourselves and to limit our exposure to formaldehyde. That's just smart. We can also put pressure on companies to please sell us healthier alternatives, even if we (meaning me actually) are scared that some of them might snipe back with accusations that we are anti-business or that we are unpatriotic.

 

The real reason why a molecule is bad for you—it's never about where it comes from.

First of all, if you look around on the Internet at all the various sources of information and misinformation about whether or not formaldehyde is actually that bad, you could easily get confused. This is because we habitually judge molecules based on where we find them, rather than what they do, and my point is that this is a bad habit. This confuses everyone! People are always asking, "where did you get that molecule?" as if the original habitat of a molecule haunted it throughout its existence, and provoked it into good or bad behavior. Formaldehyde is found in cells, in plants, in our bodies, even in floating about in outer space, plus we can make it in a lab if we want to. Does this make it good or bad?

 

All formaldehyde molecules are identical, by the way.  All formaldehyde molecules have one carbon that is attached to two hydrogens, and that one carbon is also attached to an oxygen by something called a double bond. These four atoms, when attached in this manner, are the whole thing. It is a tiny, inanimate object, without a memory or a motive, and, regardless of its origin, all formaldehyde molecules are the same and have this structure:

 

 

 

 

Stay with me here, I really do have a point with all this boring if-it-has-four-atoms-connected-in-this-exact-structure-it's-formaldehyde chemistry lecture.

 

 

It came from my body so it can't hurt you...?

Now, part of my researching formaldehyde and other molecules inevitably gets dragged down by running into a sort of disinformation campaign. It is one that tries to convince you that a molecule isn't really that bad because "it's found in your own body" or that it is "found in plants". Or you'll hear that it is bad because it was made in a nasty lab by nasty humans (even though humans are only extra-smart animals and thus a frighteningly integral part of nature, too.) What makes the Origination-Determines-Goodness argument even more confusing is that molecules found "in nature" are in every way identical to what we make in a lab if we want them to be. All you have to do is have the same connections of the same atoms, and it is the same molecule! A lab-made molecule behaves the same way as one extracted from the environment in every conceivable test as long as this is true. This has been proven unambiguously, repeatedly, since the first organic molecule was synthesized in 1828. (This was the molecule urea, which is found in your own body—it's in urine.)

 

People get very emotional about where a molecule comes from, too, and that makes me scared to recount the facts, sometimes. At one talk I even had a passionate audience member drag me aside afterwards to try to convince me that a person's intention of making a molecule, either for profit (bad) or to heal (good) affects the molecule's goodness. This notion sounds too mystical for me to imagine how you could go about scientifically testing it. Lots of money is at stake in selling, promoting or demoting and demonizing various molecules based on where the molecule comes from. But I feel I must address this repeatedly simply because it comes up repeatedly: What is most instructive to ignore where we find a molecule and just see what it does.

 

For example, the oil and chemical industry billionaire Koch brothers, whose companies incidentally profit from selling products that release formaldehyde, employ lobbyists who petition the EPA with reassuring statements like "formaldehyde is found in all organic life forms" (so are there other types of life forms? If so, please tell me about them!), and that "it does not accumulate in the environment".

 

But as you will soon see, formaldehyde doesn't accumulate in the environment because it is so unstable, it transforms into something else upon reacting with your tissues before it has time to do anything else like accumulate. Koch Industries also employs lawyers to complain about the un-American and anti-business-minded nature of any writer who quibbles with their pro-formaldehyde stance so maybe I had better watch myself here and keep to the topic.

 

This argument—that something isn't that bad because it is found in your own body—always makes me want to pound my head on my laptop. Our bodies also naturally make poo. And although E. coli is in my own body, and I will not suggest it is benign or that we should all bathe in it. Enough said.

 

Unfortunately we seem to be stuck in an old fashioned mind-set of judging the worth of a molecule by where it comes from, which is interesting, but rarely helpful. Nature makes both rash-inducing irritants and nourishing vitamins in the same plant. We know that we ought to judge people by how they behave, not where they are from, otherwise we are bigots and not very smart. We should do the same for molecules. Good questions to ask a molecule are, "Are you too stable or too unstable? Do you impersonate other key biomolecules? Do you play well with other molecules or do you destroy them randomly? How do you behave in children, animals, men, women, and the environment?"

 

How to think like a toxicologist: a molecule's structure and stability is key.

The toxicity of a molecule really does not have anything to do with where it comes from, even though some sources, like snake venom, are more reliable sources of toxins than others. The toxicity of a molecule often has to do with its structural stability, which is dependent on the arrangement of its atoms. Some molecular structures are more stable than others. Why is stability important?

 

 If you live next to an unstable neighbor, you might worry, for example. An unstable neighbor could be is more likely to play with explosives in their garage, or put weird things in your garden, and it does not matter what country they come from. Stability is not the only reason for a molecule's actions—sometimes molecules engage in identity theft, so to speak, impersonating other similar-looking molecules in your body, which can actually be either good or bad depending on the situation. But toxicity always has to do with a molecule's  appearance, it's structure, not where it is from. That's why I was going on about how "one carbon's attached to an oxygen and two hydrogens" in formaldehyde. It's important.

 

A molecule's bonds should be neither too stable nor too unstable.

Molecules have to have the right sort of stability to be benign. If they are too stable, organisms can not break them down easily, and they persist in our neighborhoods. This is only a problem if they also happen to be toxic, like PCBs, which have a structure similar to steroid hormones, and impersonate them, which ends up causing serious problems in a cell. So, it's good for molecules to be able to neatly break down and get recycled by cells of some sort of organism. However, some unstable molecules break down in a messy way that causes damage to other molecules near them. Formaldehyde is one of these, breaking down in a messy way, that like an explosion, hurts other innocent bystander molecules.

 

What determines stability has to do with what atoms are attached, and in what way. Some sorts of connections between atoms are more stable than others, and chemists learn how to recognize patterns that are either stable or unstable based on some simple rules. (If you can ever get through the grueling process of your first chemistry class, which I think is honestly the hardest chemistry class anyone can take, organic chemistry is next, which teaches you to recognize these simple patterns, and it is so much easier and more fun!)

 

The sad story of formaldehyde's naked, sticky carbon (warning: chemistry ahead. You can skip this section if you are in a hurry, but you are smart enough to understand it!)

The real reason why formaldehyde is bad for you is because the molecule is unstable, just like a two-legged chair is unstable. It doesn't matter where you find the two-legged chair, whether you buy it from a factory or make it by hand or if you happen to find it on Mars. If the chair has only two legs it will fall over when you sit in it.

 

There are two reasons why formaldehyde is unstable:

1) Its slightly positively charged carbon makes the carbon chemically "sticky", and

 

2) its carbon is more exposed than carbons in most other molecules.

 

In more detail:

1) Formaldehyde is unstable because the single carbon atom in it has what chemists call a strong "partial positive" charge. This isn't as positive as +1, but it isn't zero, either—you could imagine it as something like +0.5 but it's actual value is less important than the fact that it is not zero. For some reason (we actually don't know why!) nature predictably loves charges to be as close to zero as possible. We never see charges as high as +25 just hanging around in any object, for example. That would be very unstable and nature would find a way to mix that ridiculously positive charge up with any nearby negative charges to neutralize it, or nature would spread that large charge out over large area to make it the charge less localized and dense in one small region. We may not know why nature loves charges to be zero, but we can make fantastically good predictions about the behavior of charged things knowing that's the case.

 

That being said, some atoms comfortably tolerate small positive or negative charges and may even "prefer" (be more stable) to have charges on them (this is based on esoteric geometrical things like the atom's size and the distance from their positively charged centers to their negatively charged outer electron clouds.) But carbon just isn't one of those atoms that tolerates even a fractional charge.

 

The reason why this carbon has this strong partial positive charge in the first place has to do with its double bond to oxygen. Oxygen always pulls negative charge away from any carbon that it is directly bonded to, making the carbon less negative and therefore more positive (and if you want to know why oxygen does this, I'd have to tell you about something called electronegativity and risk losing the focus of this article.) In my mind this partial positive charge on carbon makes the carbon reactive or "sticky".

 

2) Now, not only is this carbon "unhappily" partially positive, but unlike most carbons in other compounds, it doesn't have much near it to physically block the approach of something negative that could neutralize its unstable charge. Most carbons in other molecules have bigger, bulkier atoms attached to them, like other carbons. Not only is formaldehyde's carbon sticky, but it is kind of naked, too. You can't see this in the structure above, but hydrogen atoms are the smallest of all the atoms, and the two teeny tiny hydrogen atoms bonded to the carbon are not big enough to physically shield the carbon from the interest of something that it could bump into and could bond with it.

 

The stability of massive objects like two-legged chairs is dependent mainly on the Law of Gravity. Since molecules don't weigh much, their stability is instead dominated by another natural Law: Nature's tendency to make charges as close to zero as possible, otherwise known as the Electrostatic Law. This second law, in my mind, explains almost all chemical phenomena, which is saying a lot.

 

Chemistry part over: now the biology. Formaldehyde breaks apart, crosslinking proteins.

There is a reason why formaldehyde preserves tissues. Remember that formaldehyde's unstable carbon "wants" to be stabilized by something negative? In biological tissues, the negative thing it will most likely to encounter is something called an amine. An amine is just a particular pattern of atoms commonly found around a nitrogen atom, and you can depend on that nitrogen to have negatively charged particles called electrons hanging out on it because that is always part of how an amine's structure is defined. Amines are abundant in living things, as you can reliably find them in proteins and DNA.

 

So, formaldehyde reacts with both proteins and DNA. More precisely, formaldehyde's carbon yanks on the amine's electrons and turns them into a strong bond, which helps carbon have a charge closer to zero. The remnants of the formaldehyde molecule remains unstable, so continues to self-destruct and eventually welds itself onto a second nearby amine. This bonding is the real problem.

 

Formaldehyde ties together proteins to other proteins, and occasionally to DNA too. This action is termed crosslinking. Crosslinking renders the fraction of vulnerable proteins and DNA that the formaldehyde was in direct physical contact with permanently dysfunctional or useless. If you were a protein, imagine you get some gigantic object permanently stuck to your hand. That would make you less able to perform your regular activities too, right?

 

Not only does this crosslinking stiffen and toughen the tissue and make it less likely to break down, it also makes too tough for bacteria that would like to eat it and decompose it, and formaldehyde tends to kill those bacteria, anyway, because it does the same thing to their proteins. That's why formaldehyde preserves tissues—nothing left alive can eat much of what is left of the tissues. The residual sugars, water, and small molecules remain encased in a gooey matrix of toughened, crosslinked proteins.

 

This crosslinking is all fine and good for tissue that's already dead, but what about having this activity going on in our own living tissue? Dysfunctional and useless proteins and DNA in our bodies? Should we panic about that? It depends.

 

Now, it isn't necessarily the end of the world if some of your protein or even your DNA is mechanically abused this way—it happens every day in the wear and tear of normal aging and we have evolved wonderful enzymes that zip around, repairing or breaking down and recycling our damaged molecules. (Yes, cells recycle. How about that! I am always reminding my students that cells have survived on earth for billions of years, so if we have any smarts we should copy this obviously brilliant energy strategy. Even our grandparents knew how to re-use things. But I digress...) So, our bodies can repair molecular damage to some extent. However, not all DNA damage is the same--some is harder to repair. Crosslinking is hard to repair.

 

Adducts Cause Cancer

This cross-linking form of damage involves the formation type of bond (called covalent) that is especially tough to break. The unwelcome addition to our newly appendaged molecule is called an adduct (pronounced ADD-uct). Literally an adduct gets stuck to valuable molecules and it won't come off, so those molecules malfunction. (Well, to be technically correct, the formaldehyde reaction is considered reversible and you could break the adduct off if you want to heat it to 203 F (95 C). But because it is insane to burn yourself this is not a practical consideration unless you are talking about doing that reversal in a test tube.)

 

My pulse quickens when I read about molecules forming adducts to DNA because that is usually bad news and the first thing I think is, "oh, oh, that could be carcinogenic". Adduct-forming molecules often are. (In researching the herb valerian for my book Herbs Demystified, for example, I was concerned to learn that this plant contained a molecule with an unstable bond called an epoxide. Epoxides form adducts and some are carcinogenic. However, there does not appear to be an association of valerian consumers with cancer that is statistically obvious, perhaps because valerian's epoxides may degrade too quickly to cause harm.) 

 

Examples of known carcinogen molecules that form adducts are found in tobacco smoke, burned meat (polyaromatic hydrocarbons and nitrosamines), fungal toxins (aflatoxin), certain pesticides (lindane) and even (weakly) estrogen. Even some simple elements form adducts, too, like mercury, lead, and arsenic. Some are more effective at forming adducts than others, and although our body can repair some adduct damage, obviously less exposure to adduct-formers is a good idea. The more you expose yourself, the more you roll the dice to get a cancerous cell. Why does this cause cancer, though?

 

Typically one or two permanently damaged DNA molecules doesn't cause cancer, but the more you damage, the greater the risk of cancer. DNA provides instructions for making a protein, so if you mess up these instructions you get eventually get a dysfunctional protein. What happens is that eventually you get a protein that malfunctions in that it fails to turn cell division off (the cell's brake gets stuck in the off position), or it malfunctions in that it continuously turns cell division on (the cell's accelerator gets stuck in the on position.) Either way, you get a continuously dividing cell, which turns into a mass of dividing cells called a tumor. And guess what! Formaldehyde is officially considered carcinogenic. It is most associated with "blood cancers", that is, cancers of white blood cells like leukemia. Lots of unhappy lab animals have proved that. People who work with formaldehyde in industry are statistically more likely to get leukemia, too.

 

If you just expose your skin to it or breathe it in (remember, it's really a gas) it will do some limited crosslinking of proteins in your skin and respiratory tract. So it's not surprising that it is well known to cause contact dermatitis, rashes, and irritation. Since this attracts the attention of your immune defense system, it is common to develop an allergy to it.

 

Some natural fabrics are more natural than others.

I'd always felt a bit righteous buying "100% cotton" but now I've reconsidered how I purchase my family's knickers. One of my dear friends, fiber artist and fashion designer Peter Ciesla of Bazyli Studios in Baileys Harbor, Wisconsin, recently complained that after years of professional sewing, he will no longer work with certain fabrics because of painful rashes on his hands. From now on, he said, he was doing only organic fabrics, or vintage recycled ones. "What sorts of fabrics have been hurting you?" I asked, my inner toxicologist anticipating a list of weird new synthetics. I was very surprised when he said his problem was with certain cottons, silks, and wools. What?

 

Convenience vs. rashes, it's up to you.

It turns out that, in the 50's, our desire to avoid wrinkly fabrics inspired the creation of chemical solutions that crosslink our textiles into a more compliant state. Originally formaldehyde was used. Now formaldehyde is still used, though there is less of it in modern commercial resins, with some companies like BASF even promoting an "eco" version resin with lower formaldehyde called "eco fixapret". Yet anything that is "permanent press", "easy wear", or "wash and wear" is likely to release some irritating substance which, if not formaldehyde, is related to it structurally, and will work in the same irritating manner.

 

Are you allergic to your clothes?

Formaldehyde and its releasers are the most common cause of contact dermatitis. This is according to the riveting textbook Practical Contact Dermatitis (1995, Guin), which has a whole chapter devoted to formaldehyde! If you get a rash where your clothing contacts your body closely, this text proposes it's likely formaldehyde is to blame. Do you handle a lot of clothing in your profession? My poor friend Peter's textile version of formaldehyde allergy arose after years of fingering formaldehyde releasing fabrics as a professional fabric artist. Also, this dermatology text advises if you get rashes where you sweat, since damp fabric clings more to your skin, this text suggests formaldehyde in the fabric is the culprit. Solution: tolerate wrinkly non-permanent press clothes or buy an iron. Remember those things?

 

Permanent press hair is now available and is causing the same problems.

Sophie Uliano, author of the fabulous reference Gorgeously Green, suggested I investigate the use of formaldehyde in the latest trend, a hair-straightening procedure, memorably trademarked a "Brazilian Blowout". It's also called keratin hair straightening, and is apparently immensely popular for women who just want their hair straight. Even though it only lasts about three months and costs a pretty penny, some women who can afford it love it, and have it done regularly. However, there are also plenty of women complaining about how it has caused rashes and even serious breathing problems following the procedure.

 

Intimidated by beauty salons, I'll confess I shy away from them, trimming my own hair the low tech dorky way (admittedly badly) with scissors and a mirror. So I knew nothing about this procedure, of course. And when I told my husband that I needed to learn about  Brazilian Blowouts he perked right up and waggled his eyebrows suggestively at me. He didn't know what it was, either. We are both dorks.

 

I was in luck because our peninsula is now abuzz about a brand new ecological beauty salon opening in Egg Harbor, Wisconsin, Spa Verde, conveniently next to our local health food store, Greens N' Grains. And I just happened to know the lovely stylist managing the salon, Andria Nikoupolis-Weliky, so I thought she'd be the perfect person to ask about this procedure.

 

Andria said she felt compelled to open the salon because she felt so worried about the health risks from exposure to common salon products that she had herself used for years. I have no experience with nail products, because I play the harp and trim my nails down to oblivion to prevent unpleasant string clicks. Yet I do have friends with beautified nails that continually irritate them. Andria informed me that several brands of nail polish are particularly problematic for women. Andria said her salon uses alternative polishes that don't have formaldehyde or their releasers. So, healthier options for nails are available.

 

I asked Andria what she would do if a woman came into her salon and asked for this Brazilian Blowout, or keratin straightening, or whatever you want to call it. She said she would partly counsel the woman to find out what she really wants. It would be a lot easier to start with someone who was comfortable with whatever hair type they already have, she confided. She would encourage the person to learn to be comfortable with who they are and the hair they were born with. But if this sort of personal counseling failed, and a curly-haired woman insisted on having straight hair, Andria would be honest with them and tell them their ecological options. She'd use traditional and non-toxic methods like a flattening iron and non-toxic hair care products—which would need to be repeated after every shampoo.

 

So, more work would be involved, just not unlike non-wash-and-wear clothing. But here is how I think about it: it may be less work to use a flattening iron every day than to cure yourself of leukemia, or even deal with painful rashes and breathing problems, in the long run. And learning to cherish whatever hair type you were born with is maybe not such a bad thing.

 

There is confusion about whether or not some of these keratin straightening procedures have more formaldehyde than others, and some even claim to not have any. Again, the problem is similar to the wash-and-wear clothing. In order for the procedure to work, you need a chemical reaction that involves either formaldehyde or molecules that have structures that work similarly, which is the root of what causes the rashes in the first place.

 

Formaldehyde in cosmetic products

I was out shopping and pondering formaldehyde, and coincidentally ran into my dermatologist, Dr. Diane Thaler. I used that opportunity to probe her knowledge of the chemical. She surprised me by revealing that it was indeed in several cosmetic products, causing her to change brands of shampoo during medical school, because the formaldehyde-containing ones made her head itch uncontrollably.

 

Wait a minute! I thought. I am an obsessive label reader. But I didn't remember ever seeing a bottle of shampoo or lotion or any sort of cosmetic product with "formaldehyde" on the ingredients list. That would be like seeing the word "carcinogen" on the label. I would have remembered that! What was going on?

 

When formaldehyde-free isn't

 Diane's helpful references led me onto the trail of "formaldehyde releasers". They are not formaldehyde, but because they break down and release formaldehyde over time, they, like formaldehyde, increase the shelf stability of the product. That is how a product can expose you to formaldehyde and not have formaldehyde on the label. Quaternium 15, for example, is one of these, and according to my contact dermatitis textbook, it's the most common cause of contact dermatitis found in cosmetic products.

 

Here's a list of common formaldehyde releasers:

para-formaldehyde

hexamethylene tetramine

DMDM hydantoin

polynoxyline

dimethylolurea

preventol D1

preventol D2

preventol D3

quaternium 15

bakzid

bakzid P

parmetol k50

grotan BK

imidazolidinyl urea

diazolidinyl urea

2-bromo-2-nitropropane-1,3-diol

KM 103

biocide DS 5249 (Proxel T)

tris hydroxymethyl nitromethane (Tris nitro)

hydroxymethylglycinate (Suttocide A)

 

 

Now, I sympathize with the desire to use preservatives, but there are smart ways of doing this, and not so smart ways. My first attempt at creating hand lotions in order to promote a local artist's work--her art was on the label--failed. I thought that vitamin E would preserve the product, but I should have added more, and perhaps used an additional backup. It turned out my all-natural ingredients were so yummy to various airborne fungi that several of the containers were quickly colonized with fuzz. I had on hand many all-natural petri dishes. I had to toss them. Damn those microbes, for they must have had a ball feasting upon all that expensive organic shea butter.

 

But there are ways to make products less appetizing to microorganisms by playing with more variables, and I am sure I didn't need a formaldehyde releaser to do the job. You can start by making a cosmetic product too acidic, too basic, too minerally, too dry, or too salty for most microbes to want to live in it, for example. Some "natural" cosmetic products are also preserved by pungent plant oils, although these can be just as irritating to your own cells as to microbial ones, though, because the mechanism works the same way on both cells (fragrant molecules called terpenes tend to dissolve cell membranes). If you have sensitive skin, it really does make sense to avoid even "natural" fragrances. Like I've said before, the origin of a molecule doesn't determine it's behavior.

 

How to reduce formaldehyde in your home—use green alternatives.

The most common source of formaldehyde in homes is from certain adhesives used in pressed wood products. The glue is either a formaldehyde-urea or phenol-formaldehyde resin. MDF, or medium density fiberboard, has the most resin per wood, and is therefore the worst offender. Other formaldehyde releasing materials include particleboard, hardwood plywood paneling, softwood plywood, and flake or oriented strand board.

 

Formaldehyde in buildings hit the media radar after thousands of residents of FEMA trailers inhabitants complained about difficulty breathing, asthma, and allergic reactions. About 83% of the trailers were found to have formaldehyde concentrations greater than what the EPA recommends.

 

Luckily, consumer demand has made widely available—as in your local Home Depot or other big box store—building materials made with alternative glues that don't release formaldehyde. As always, look at the label and do a little research before you buy. The more alternatives we demand and purchase, whether it is plywood, shampoos, or clothing, the more industry will listen and profit, and no one will get hurt.

Should you boost glutathione, and if so, how?

   

   

          A dear friend of mine was recently diagnosed with rheumatoid arthritis, and wrote me:

Dear Holly,
I was just thinking of you and wondering how you are doing. I also was wondering if you would mind checking some thing out that some friends informed us about. It is a product called max GXL. It helps with the production and preservation of Glutathione which I have never heard of. There is an interview with the man who came up with it that I thought you might find interesting. I am very curious what you think. The web-site is (edited out by me)

Here's my reply:

That is funny, I did my graduate research on glutathione, which is a natural antioxidant made of three amino acids bonded together, found in all of our cells. I was trying to invent new drugs that increase it.

So I can tell you all about that, I got my PhD on the topic. And yes, I think glutathione is a wonderful thing!!! It is depleted in many diseases and also helps our bodies get rid of toxins, as well as being a general antioxidant. But don't buy it from that company. They are charging way too much, and in my opinion taking advantage of sick people. Over 60 bucks for less than a months supply of pills? Slimeballs!

I HATE it when supplement companies take advantage of sick people.

Not everyone needs to increase glutathione. Actually, I don't think taking supplements that boost glutathione will do a thing unless you are depleted of glutathione in the first place. That is what we find when it comes to taking antioxidants in general. But in your case it can't hurt to try something that will ensure your glutathione levels are up to normal. We find that glutathione is depleted in many chronic diseases and in cases of acute and long term poisoning. In those cases, increases glutathione to normal levels does help!

You can't really boost glutatione above normal, without it being recycled, but you can increase to normal levels that were depleted. (Of course, also keep up with your regular treatment of a healthy diet and lots of exercise!)

For a while I had a miserable job of poisoning hundreds of mice with acetaminophen ("Tylenol"), and then saving a portion of them form dying a horrible death of liver failure with either new drugs that I had synthesized or a standard treatment that boosts glutathione (called "NAC".) I did similar things to liver cells in culture dishes, (which are easier to deal with, emotionally, but less like people). NAC did tend to save the lives of the poisoned mice and liver cells, and it is what I will recommend for you.

You might be wondering, if you want to boost glutathione, why not just eat glutathione? The problem with taking glutathione itself is that it gets broken down when you eat it, before it gets into your cells. Your body might put a portion of it back together, a little bit, after eating it, but eating it isn't the most efficient way to get it, ironically.

The best stuff on the market for increasing glutathione, that I know of from research, is called N-acetyl cysteine, also abbreviated as "NAC". It may also be called "L-NAC", which is exactly the same thing. The second best thing for increasing glutathione is L-cysteine, also called cysteine, but I would not recommend that since large doses can cause nerve damage. NAC is a slow-release form of L-cysteine and is safer.

Although I don't usually take supplements ( I prefer to just eat lots of nice-tasting herbs in my food!), I have taken NAC on occasion,  perhaps because I was made curious by my own research, but then I never knew if it was doing anything. At least I never had any side effects. Reasonable doses certainly can't hurt, unless you don't need it, in which case it hurts your wallet.

I'm also put off by the lack of regulation of the whole herb and supplement industry, so at the risk of saying this for the millionth time, I wouldn't take anything unless I checked out the product first with an independent lab that evaluates various supplement products, called Consumerlab. (You can find them at consumerlab.com. and search their database with a yearly subsciption fee which is fairly inexpensive, I think.)

Sadly, consumerlab has not yet evaluated NAC or other glutathione-boosting supplements just yet. However, NAC is fairly easy to synthesize and purify, although it does oxidize a bit over time. The oxidized version of it in the supplement is unlikely to hurt you, anyway (but less likely to work.)  Unlike herbs, which are easily contaminated with pesticides and vary quite a bit in the concentrations of active ingredients, a bottle of NAC ought to be fairly pure. It also ought to be far less expensive than the product on that website you asked me evaluate.

At our local health food store, NAC should not be more than 10 bucks for a bottle of pills, I'm guessing. It was dirt cheap from the chemical companies our lab bought it from, too, so there is no reason for these supplement companies to inflate its cost.

I would definitely avoid any NAC combined with other ingredients, however. You don't know what those other ingredients may do.

I hope that helps!      

 

Will licorice really raise my blood pressure? How?

Hi Holly,
My doctor tells me that licorice can make my high blood pressure worse. Is that really true? How does that work?

Licorice lover in L.A.

It might. The mechanism is complicated, but I think it's a fun one! (OK, I perversely enjoy complicated mechanisms.) And you can certainly understand it if you want to hang on and read below. For even greater detail, with published references, read my licorice chapter from Herbs Demystified.

The occasional licorice induced hypertensive crisis does occur, typically with already hypertensive folks sitting around eating gobs of licorice every day for weeks at a time having to be admitted to the emergency room. This sort of crisis isn't all that common, however.

That's because you have to consume a lot of licorice, and it has to be REAL licorice. Most of the licorice sold in the US has had its active, blood pressure-raising ingredient removed. If you look at a product label for US licorice, you will often see the term "de-glycerrhizinized licorice". This sort of licorice won't raise your blood pressure.

In fact, a lot of US "licorice" candy has no licorice in it at all, and is flavored with similar tasting anise! (Anise, and fennel, for that matter, do not have this active ingredient, although they all taste similar.)

Europeans have always preferred real licorice. I can find it in some European import stores in my neighborhood, and it is some pretty strong stuff! (For an added hypertensive kick, the imported, Scandinavian type of licorice has a ton of salt added to it! It's an acquired taste.)

Also, the demand for real licorice in the US is rising, and you can now find in health food stores marketed as "real" licorice candy. Certainly a lot of "herbal" teas which are not labeled "licorice" still use licorice as a sweetening ingredient. You would have no idea licorice is in it unless you looked at the list of ingredients.

I mention this since one case study involved a man who drank a several cups of a tea containing licorice every day for years before he went to the emergency room.

The active ingredient in licorice root is a steroid-like, sweet tasting molecule called glycerrhizin. (Yes, it looks like Welsh to me, too.)

Glycerrhizin overdose mimics a syndrome called "Apparent Mineralocorticoid Excess". This can result in a trip to the emergency room where a patient presents with a crisis resembling an excess of the hormone aldosterone. Aldosterone causes you to retain sodium and pee out potassium, and it raises your blood pressure.

Scientists used to think that licorice simply mimicked aldosterone, especially since it LOOKS like the steroid hormone aldosterone. That's a very reasonable conclusion, but it's wrong!

The mechanism is a bit complicated, but basically glycerrhizin turns off a class of enzymes called "short chain dehydrogenase reductases", or SDRs.

Interestingly, one effect of turning off these enzymes in you gut is that the gut makes more mucous and less acid (the SDRs would otherwise disable prostaglandins that do this trick) so it does seem likely that real licorice can help soothe an inflamed gut.

On the other hand, the glycerrhizin turns off the SDR enzyme that ordinarily keep cortisol from acting on the kidney. Since cortisol acts just like aldosterone, binding to aldosterone receptors on the kidney, and cortisol levels are a lot higher than aldosterone, normally, this causes the kidney to "think" that aldosterone is sky high. Cortisol in the guise of aldosterone causes potassium loss, sodium retention, and consequent water retention with hypertension.

From what I can tell of all the case studies I've read of licorice eaters going to the emergency room, it takes a LOT of licorice to do this trick. So the occasional moderate snack of real licorice probably isn't going to hurt.

So, if you do have high blood pressure, perhaps you should have de-glycerrhizinized licorice, rather than real licorice, or keep your consumption of real licorice down to reasonable levels.

I hope that helps!
Holly

What can I take to decrease a PMS-associated prostaglandin?

Hi Dr.Phaneuf,

First of all I'd like to say that I'm not a science student or any kind. But lately I came accross this Prostaglandin F2 alpha (PGF2a) thing.
I read it somewhere it said that elevated level of PGF2a causes Dysmenorrhea ?
Is it true AA [Arachidonic Acid (an omega-6 PUFA)] can be found in linoleic acid (LA)? But isn't AA can be found mainly in animal only (errmm..said wikipedia) and LA is abundant in vege oil like olive, sasame, etc?. So which is which? My home usually cook with red palm oil.
What sort of herbs stimulate or has PGF2a or has AA then (since AA is the precursor of PGF2a, yes/no?)?

Thanks!
Not-a-science-student.

Hi Not-a-science-student!
Well, for someone who “isn’t a science student”, you are asking a pretty sophisticated and important question.

You can get my book from a library or you might enjoy irritating Barnes and Noble by leisurely reading it in their lounge with a nice latte without committing to buy it. Then just look up the flax seed, evening primrose, and borage seed chapters, and you will see more than you probably ever wanted to know about how these fatty acids like linoleic acid and arachidonic acid get converted to different prostaglandins. But to save you from this, I took some excerpts from my book below, and added more to address your specific question:

I don’t like to tell people what they should and shouldn’t take (there are enough people out there doing that already!) but instead I like to look at the cause and effect molecular mechanisms by which a substance works. Some mechanisms are better for some people than for others.

Also, we can’t judge a substance based on where it is from—any more than we can judge a person based on where they are from—that isn’t helpful or informative. You judge them based on what they do, and how they do it! So regardless of whether it is from “nature” or a lab bench (I argue that people are animals and part of nature anyway so this distinction doesn’t mean much to me) I just look at the mechanism and ask, is this an appropriate mechanism for your individual body? It does seem, however, that I keep finding that it is better for us to get more of our food from plants than from animals. You at least seem to be trying to do this with your red palm oil--that's good!--but you could make some better choices for oils.

But let’s get some terms defined, first.

You wonder if a certain prostaglandin causes menstrual problems, and the short answer is, that particular prostaglandin you mention (PG F2-alpha) might. It is used as a medication to induce labor and causes uterine contractions, or what you might call “cramps” when you make it all by yourself to your dismay. And yes, the sources of that particular prostaglandin are omega-6 fatty acids such as linoleic acid. The most abundant omega-6 fatty acid in our diets is linoleic acid (LA), which our body can convert to arachidonic acid (AA) (another omega-6), and then that under certain circumstances can get converted to this particular prostaglandin (F2-alpha).

So, it isn’t true that “arachidonic acid is found in linoleic acid”—it is true that linoleic acid is readily converted to arachidonic acid in our bodies after our enzymes tack a couple of carbons onto the chain, lengthening it from 18 carbons to 20 carbons. So linoleic acid is a precursor to arachidonic acid. (Both are found in meats to some extent, when the livestock eats plant sources of them.)

Your red palm oil doesn’t have the glut of linoleic acid that other vegetable oils like corn oil, safflower, and sunflower oil have, but it does have about 10% from what I can see. It also has a lot of saturated oils, which are not essential, and these won’t oppose the conversion of linoleic acid into arachidonic acid, which is what you appear to be rightly concerned about.

If you want to oppose the action of linoleic acid metabolically speaking, you would be better off getting more omega-3 fatty acids from your oils. Flax oil, walnut oil, and fish oil (from fish or fish oil capsules) are excellent sources of these.

Although I’m not in the business of telling people what they should and shouldn’t take, there are times when I am compelled to shout out about what might obviously help a lot of people! Lots of nutritionists and health care professionals are concerned that we eat too much linoleic acid, which is an omega-6 fatty acid, and not enough of the omega-3 fatty acids. I used to be skeptical about this, when the topic was raised 20 years ago! But after reading lots of boring scientific research articles on fatty acid metabolism, I’ve been thoroughly won over by this argument, too.

I admit it; it’s really an oversimplification for me to classify all omega-6’s as “bad” and all omega-3’s as “good.” The problem is their ratio in our diets. If you look the assortment of fatty acids in the modern diet, the “rare” essential fatty acids are the omega-3’s, and this has some health experts worried. They argue that our diets once possessed a 1:1 ratio of omega-6 to omega-3 fatty acids that is now skewed in favor of omega-6’s as high as either 10:1 or 20:1, depending on which expert you talk to. Modern society has recently become so adept at harvesting and using certain vegetable oils—corn oil, safflower oil, soybean oil, and sunflower oil—and these are all loaded with the omega-6 fatty acid linoleic acid. This we to feed to our livestock in the form of corn, a source of omega-6 oil, rather than their preferred grass, enabling even our commercial meat supply to be unbalanced with omega-6’s. Grass-fed livestock has more omega-3’s. Omega-3’s are abundant in fish oils and flax seed oil, and present to a lesser extent in other vegetable oils and nut oils.

So what’s wrong with eating linoleic acid? You do need some linoleic acid because you can’t make it. This puts it in the class of “essential” fatty acids. Obviously it’s better to have essential fatty acids than the non-essential ones that we already make, like saturated fatty acids. These are the infamous artery-clogging agents found in animal fats. Possibly even more menacing are the relatively unnatural “trans” fats created by partially hydrogenating oils, that many fast and processed foods are now dripping with, and like saturated fats, these are also tied to health problems. On the one hand, people who have more essential fatty acids than non-essential ones generally fare better, health-wise.

On the other hand, some essential fatty acids are healthier than others. The proportion of linoleic acid in our diet is disproportionate compared to other essential fatty acids. A glut of one type of essential fatty acid drowns out the beneficial actions of the others.

This is where people start talking about those omega-3 fatty acids and omega-6 fatty acids, which we have to get in our diet, because we can’t make them, and so they are called “essential”. These have some obvious fates after we eat them. Either they get “burned” into carbon dioxide for energy, or we will merrily stash them away as fat, regardless of our opinion about that, and they also get readily incorporated into the material making up our cell membranes—the outer boundary of our cells. Indeed, you can see what sort of fatty acids someone has been eating by looking at whether their cell membranes contain omega-3 derived fatty acids or omega-6 fatty acids—you really are what you eat.

The reason the terms 3 and 6 are used is because it matters whether an prostaglandin is made from one or the other. The “3” or the “6” indicates the position of something called a double bond in the fatty acid. The reason we care about that is that that position tends to stay in place as the fatty acid gets chemically changed in our bodies. So, an omega-3 will remain an omega-3 as it is transformed into other fatty acids, and an omega-6 will remain an omega-6 as it is transformed into other fatty acids. Thus the ratio of the kinds that your are eating will be preserved even after they are chemically altered into other fatty acids by your body.

The prostaglandins are part of a larger group of similar molecules collectively called eicosanoids. The “eicos” means 20, as they are all formed from fatty acids that are 20-carbons long.

Keep in mind that both omega-3s and omega-6s compete for the same enzymes to convert them to other more physiologically active molecules. So by eating more omega-3's, you can slow down and reduce the conversion of omega-6's into things like that prostaglandin you are worried about.

Eicosanoids, classified as prostaglandins, thromboxanes, and leukotrienes, work only briefly in tissues nearby where they are generated, and are thus called “local” hormones. Nonetheless they have powerful and often opposing actions on blood pressure, blood clotting, pain and inflammation, allergic and immune responses, uterine and gastrointestinal cramps, digestion, brain development and mood, even tumor development and growth...in other words, just about everything you can think of!

Both classes of essential fatty acids, the omega-3’s and the omega-6’s, are used to make 20 carbon fatty acids, which are transformed to hormone-like eicosanoids. The types of essential fatty acids you have stored influence what types of eicosanoids you tend to make. At the risk of oversimplification, I’ll come to the punch line: the omega-6 fatty acids generally make more pro-inflammatory, damaging eicosanoids. Eicosanoids derived from the omega-3 fatty acids are more anti-inflammatory and protective. Inflammation is just our protective systems gone overboard, so to speak, so the omega-6 system of eicosanoids isn't bad, it just seems that we are overdoing it with with the supply of omega-6 in the modern diet.

Alpha-linolenic acid, or ALA, is the main omega-3 fatty acid in flax seed oil, and you can readitly turn it into at least one valuable fatty acid found in fish oil. ALA gets incorporated into your cell membranes and fat after you eat it, so you store it. Ignoring minor pathways, it has two general fates: it can either be “burned” for energy, or turned into another omega-3 fatty acid. This is typical: omega-3 fatty acids, when metabolized by your enzymes, can only be turned into other fatty acids of the omega-3 class, and omega-6’s can only get turned into other fatty acids of the omega-6 class.

The 18-carbon ALA is lengthened by 2 carbons and 2 more double bonds are added, to make eicosapentaenoic acid, or EPA. This is one of the essential fatty acids in fish oil that everyone is now raving about for its health benefits. If you haven’t heard lately that nutritionist want you to eat more fish oil because of its omega-3 fatty acids, you’ve been living on another planet. If you don’t eat fish, you can make at least one fish fatty acid, EPA, by taking flaxseed oil. Why is EPA so exciting?

Medical professionals are rewriting the textbooks, literally. We are only now becoming aware of how important EPA derived eicosanoids are. In fact, if you look at even relatively recent medical textbooks, they only discuss ones derived from the omega-6 fatty acid, arachidonic acid, and barely mention the ones derived from EPA. Most texts are now being revised to include discussions of their activities, fortunately.

EPA derived eicosanoids perform the following healthy tasks. EPA is used to make the following menu of eicosanoids: prostaglandin E3 (PGE3), prostacyclin I3 (PGI3), thromboxane A3 (TXA3), and leukotriene B5 (LTB5).

Now here is what the omega-3 derived eicosanoids do. Hold on, this is a lot of data:

PGE3 has an anti-inflammatory mode of action similar to that of steroids like hydrocortisone: it prevents the omega-6 eicosanoid precursor arachidonic acid from being liberated from cell membranes, thus halting its conversion into inflammatory omega-6 derived eicosanoids. In addition, PGE3 reduces intraocular pressure, so scientists are now looking at it as a possible glaucoma treatment.

PGI3 is anti-inflammatory by the same mechanism: it prevents arachidonic acid release, plus it potently inhibits blood clot formation.

While the omega-6 arachidonic acid derived thromboxane, TXA2, makes platelets sticky, potently forming blood clots and narrowing blood vessels, the EPA-derived TXA3 is relatively inactive and competes with it.

Similarly, the leukotrienes derived from omega-6 arachidonic acid are countered by the leukotrienes made by EPA. The leukotrienes made from arachidonic acid (such as LTB4) mediate the distressing bronchoconstriction in asthma, as well as chronic asthmatic hypersensitivity and acute asthma attacks. They are also involved in the inflammatory processes seen in disorders like cystic fibrosis, inflammatory bowel disease, and psoriasis. Although the leukotriene B5 derived from EPA also signals the immune system, it does so more weakly by an order of magnitude, and competes with formation of the more inflammatory leukotrienes. Thus it tames the immune system’s response, without shutting it down.

You can’t easily turn flax seed oil’s ALA into the second valuable fatty acid in fish oil, at least not very well. I write this to correct a common misconception still bandied about the nutritional literature. Fish oil’s other valuable omega-3 fatty acid is the 22-carbon long docosahexaenoic acid, or DHA. Although humans have enzymes capable of turning ALA into DHA, human studies repeatedly show that we just don’t do it very well, though some sources (often associated with flax oil sellers) glibly say that you can. This is frustrating, if you realize how important DHA is, and if you don’t eat fish oil!

Recent data suggest maybe this is because excess linoleic acid (the omega-6) opposes this conversion, so maybe you can convert ALA to DHA if you lower your linoleic acid intake enough. So that's potentially good news for the non-fish eaters out there, (and good news for fish) but I am waiting for more data to see that hypothesis can be better supported.

DHA is not used to make eicosanoids (it doesn’t have the prerequisite 20 carbon length chain for that) but it is of startling importance in the brain’s growth, development, and signaling, as well as retinal function. Because of the growing awareness of our requirement for DHA and our limitations in making it, some are now suggesting this fatty acid is essential on its own, because ALA isn’t a very good precursor to it. There are even interesting theories about how pre-hominids required moving from the trees to an environment next to water, to obtain a source of fish. This supposedly helped them to evolve better brains, but I am not an an anthropologist.

I am not sure what to recommend to strict vegetarians because of this, and I do sympathize (I’m a vegetarian, but I joke that I am now a bad one because of these studies I have read—I’m not a strict one, and I take fish oil. And OK, I like to eat fish!) It’s possible you can make some DHA from flax seed oil, but don’t expect to make a lot. The fish oil has omega-3s simply because certain fish eat certain cold water algae, which supply the fatty acids themselves. So maybe we can just grind up some vat grown algae in a blender and mold it into the shape of a fish and not hurt the ocean's ecology. I'll eat it, I'm easy.

I may have gone a bit off topic there, but there is so much to say about these interesting essential fatty acids! Somebody shut me up! So try getting more omega-3 oils from one source or another, and limiting your linoleic acid intake. I hope that helps!

Cleansing the GI tract for body odor?

Hi Holly,
I came across your site today and filled with awe of how much you know. Therefore I would like to ask your for your insight concerning an issue, most people I came across on the internet, are silently suffering from.

I am aware of apocrine glands in the armpit and ano-genital area. I do know that when one sweats in these regions, if it mixes with bacteria, it would give off offensive odors. What I don't understand is that, even though when some people wash off the sweat, and apply deoderant and antiperspirants, there still seems to be offensive odor given off.

I have also noticed that after taking a shower, maybe 5 minutes of more, I might start to give off odor from the armpit. I have tried various remedies I came across online, to no avail. I currently use an antiseptic soap and dove, but the issue persists. This is really affecting me psychosocially, physically and so on. I always dreaded going to class because I noticed some of my classmates could perceive the odor(by their body languages).

I came across a site called drnatura.com, have you heard about it and what do you think about one cleansing out oneself? They say that it is good for one to periodically cleanse out the GI system, and toxins from the other systems in the body. I am thinking about giving it a try, to see if it rids me of this odor. By the way the odor recently started towards the end of spring '06. I don't sweat excessively (no hyperhidrosis), its the odor i'm concerned about.

I also recently noticed/feel some excessive heat inside me (whole body). Its quite uncomfortable, but when my temperature is obtained, it is usually within normal limits. My labworks seem to be normal i.e. thyroid studies, liver functionand so on. I went to see my doctor regarding the armpit odor issue,and asked for a refferal to a dermatologist. The doctor simply disregarded my request, and informed me that she'd consult the dermatologis herself. I received a note from the doctor to limit fat/salt/cholesterol intake, which I don't often consume.

There are numerous people whom I came across that suffer from this issue. I truly would appreciate it if you could give me some advice.
thanks

Well, thanks for the praise, but I don't know everything. That is why I have to constantly look up stuff all the time and re-evaluate what I think I know! I recommend some of the sites on "relatively reputable resources", in the margin of my website, here.

I am sorry to say it, but as appealing as the idea of cleansing your GI tract may sound, an unclean gastrointestinal tract is not your problem. "Cleansing your GI" will not help you one bit, it will just clean out your wallet. It is a popular fad based on a medieval notion that some sort of undefined "toxins" (they never give them actual chemical names so I can look them up!) in the body are causing problems, and need to be cleansed with attacks from above and below with laxatives and enemas, or other devices. The idea has not a bit of sound scientific evidence to support it, although it is an easy thing to picture, especially for medieval minds.

To read more about GI cleansing, take a look at Dr. Stephen Barrett's article. (I especially like the protest from a colon cleansing enthusiast that he politely adds at the bottom of his article, pretty much handing the poor person a rope that they then gleefully hang themselves with. It is filled with grammatical errors, conspiracy claims, and the eyebrow-raising claim that our intestine has a BRAIN! I must have missed that one in my anatomy class.)

For further reading on popular scams in general you might want to check out my own article, How To Avoid Getting Conned by People, Including Yourself.

The good news is that I really think a dermatologist can help you. I know you say you don't have problems with excessive sweating, but you might want to check out possible treatment with botox injections, which can control sweating. I'm not sure what the verdict is on using that for odor, but I understand it is a life saver for some who have excessive sweating. If your dermatologist doesn't help, see a different one. Of course, we will assume you are bathing every day!

I'd also recommend seeing an endocrinologist. I am not sure what you mean by "excessive heat" in your body. You have not revealed your age or if you are female, so that may make sense if you are entering menopause, which can happen prematurely for some women. Whether you are female or not, an endocrinologist will be better than your average MD at sorting out any hormonal imbalances that may cause a sensation of heat or overactive apocrine glands. If you have a fishy smell, you may have a relatively rare genetic condition that you should get checked out by an MD.

I hope that helps you get started on the right path! Now make peace with your colon!

Holly

Rethinking antioxidant supplements

Dear Dr. Phaneuf,

You describe very clearly how antioxidants protect our cells, and in your book you also describe which plants have interesting antioxidants and how they work, but when it comes to people taking antioxidant pills, you become suddenly skeptical to the idea. How do you reconcile these points of view?  -Lucas

Hi Lucas,

The bottom line is this: I still am excited about antioxidants, don't get me wrong. But antioxidants in pill or supplement form don't do anything dramatic according to the best clinical studies. Not only are some very expensive, but large doses of them turn them into free radicals and oxidizing agents, the very thing you are trying to avoid, by taking them.

If you don't understand how an antioxidant can turn into an oxidant, it is very simple, and I explain it in how antioxidants turn into oxidizing agents (click here).

First, you need to know that oxidizing agents and free radicals (which are often the same), generally known as ROS (reactive oxygen species) are an unavoidable consequence of cellular respiration--and these ROS do damage to our cells. It There is good evidence that these ROS may initiate many of our common diseases and general aging. Antioxidants (which chemists call reducing agents) neutralize ROS by a variety of mechanisms.

People who eat a lot of fruits and vegetables are less prone to diseases--the very diseases that we think may be caused by oxidizing agents. Now, people have formed a logical theory that since plants contain many antioxidants, these antioxidants are combating ROS and their associated ill effects. But hold on to your hats--this is just a theory and it may be all wrong!

We actually don't really know why people who eat a lot of fruits and vegetables live healthier lives. Perhaps the many studies are "confounded"--that is, what else do people who eat lots of fruits and vegetables do? Probably exercise, buckle their seat belts, avoid smoking, and all that. We try our best to statistically weed out confounding factors in these observational studies, but if you are a good scientist, you have to be honest and admit that some confounding might be going on.

Just because you can imagine a great mechanism, and see it take place in a test tube with isolated cells, does not mean that same mechanism will work in a person.

Well, here we were with this lovely theoretical mechanism for how antioxidants from plants could be helping us live longer lives. So based on this theory, isolated antioxidants in pill form ought to be great, right?

Wrong! We all held our breath for years as study after study came out, testing everything from classic antioxidants like vitamins E and C, to more obscure polyphenols and glutathione and so on. Nothing that dramatic appeared. For the most part, the only time you saw a noticeable effect is when the lab animals or people started out with a deficiency in the item tested to begin with. In some cases large doses of antioxidants proved harmful--one of the most dramatic cases was with beta carotene significantly increasing cancer among smokers, to the point that the investigators had to pull the plug on the study to save the participants. Large doses of tannins may cause cancer. Large doses of quercetin make you dizzy and make you throw up, and can cause tingly nerves in the extremities.

As someone who has synthesized and tested antioxidants in the lab, and been in on some of this research, I can't tell you how disappointing this has been for me.

But nature is always trying to tell us the truth through the data, I believe, and you always have to look especially hard at data that you don't like, because it might be telling you something even more wonderful than your previous conceptions allowed. Nobody likes to toss out their pet theories. But science forces us to do this repeatedly. I really trust that the truth is in good data, even data we don't personally like.

So for now it seems like a good idea to just eat your fruits and vegetables,drink tea and/or coffee (with or without caffeine) and put your favorite cooking spices and herbs on your food to flavor it. I would definitely skip the supplements.

Now, why might antioxidant pills be so ho hum in clinical studies? There are lots of good theories:

1) Targeting to mitochondria

One of the most intriguing theories, to me, is that antioxidants don't work unless they get to the very place where they are most useful--the mitochondrion. This is the cellular structure where respiration takes place. It is where about 90 percent of our oxygen gets used. This is the place where most of the harmful ROS are generated. Even cells in culture with antioxidants dumped on them may absorb the antioxidants, but the antioxidant still doesn't get inside the mitochondria in the cells.

Recently, chemists have synthesized antioxidants that are targeted to mitochondria. That is, they have given them chemical mailing addresses, so to speak, that help deliver them to the mitochondrion. (Actually, this is just a consequence of electrostatic forces--the inside of a mitochondrion is mostly negatively charged, and they put permanent positive charges on these antioxidants, and since negative attracts positive, the force of the charge pulls the drug into the mitochondrion.) So far no people, to my knowledge, have taken these mitochondrially targeted antioxidants, but they are getting positive results in studies with cells and rats.

2) Absorption into the bloodstream

Antioxidants in the polyphenol class in particular, including flavonoids, are notoriously bad at making a one way trip through your digestive tract, down to the bitter end. Many are physically large, and bind to proteins in your gut in some cases, literally "tanning your  hide" in your gut in the case of tannins. Resveratrol in grapes is SO exciting--in test tubes. But just try to get that sucker into your bloodstream. OK, some trace amounts can get through, but those then are swiftly metabolized into other things. It may still be that their action in the gut alone is not to be dismissed and is helpful. Some scientists have proposed that in plant foods, the fiber of the food slows the release of such polyphenols so they are absorbed more efficiently, as opposed to in pill form. That is a good theory, but remains to be tested.

3) We actually need oxidizing agents and free radicals.

I have had to laugh out loud at some supplement sellers, who paint all free radicals as bad, if not actually "evil"! One described free radicals as "having only one purpose, to destroy you"!  (Just a note--chemicals are not alive and have no purpose, and can't really be regarded as good or evil).

It would have indeed raised the eyebrows of the writer of this alarming passage to learn that many free radical scavengers work by becoming stable free radicals. So, these stable free radicals are actually helpful. Also, we need free radicals in the right places--we need a smattering of nitric oxide in our blood vessels, which is a free radical and a simple gas, as a very important hormone like molecule that lowers our blood pressure and performs so many other important functions.

So it is not that free radicals and ROS are "bad" and antioxidants are "good", but we need both, in the right places, and in balance with each other.

4) Plants also contain ROS. Maybe these are helpful.

Plants make all sorts of toxic things, often functioning as insecticides and antimicrobials (since they can't run away from insects and pests, they tend to synthesize some nasty chemical weapons). That is one reason why, as a chemist, I find plants so fascinating--they are much better synthetic chemists than I could ever hope to be. Not only does coffee and and tea--my own favorite plant derived products--contain a lot of antioxidants, but they also contain ROS like hydrogen peroxide! One theory is that these ROS kick-start our defensive processes like the induction of the synthesis of new antioxidant enzymes.

The bottom line is that the story is never as simple as the supplement sellers would have you believe--but it is far more interesting!

Cocoa butter for the pregnant?

Dear Holly,

I recently just found out I am pregnant with my second child.  When I went to my OB/GYN today he told me to no longer use cocoa butter.  The reason being that it contains caffiene and it has been known to cause irregular heartbeats in fetus' and infants.

Women have been using cocoa butter for centuries and I don't know what the difference is now. 

Can you find out if this is being told to others and if I should stop using the product.

Thank you

LR

Dear LR,

Keep enjoying your cocoa butter. It sounds like your doctor means well but is misinformed. I can relate; at the risk of losing your confidence I will confess that I am constantly making flight corrections in my thinking, because what we learn from new studies always forces us to look at the data anew! Nature shows us the data, and we have to keep our minds open in order to see what she is trying to tell us.

I have some research articles below that your doctor can read to clarify the points that I make here, if they are open to such a thing.

First, cocoa butter contains no caffeine.

So relax and enjoy your cocoa butter. If it is not processed completely it might contain teensy weensy iddy bitty little traces of caffeine that are entirely negligible in concentration; and these would be too scant in concentration to affect you physiologically, unless you spent all day eating multiple vats of cocoa butter.

Cocoa butter is mostly saturated fat, but does not seem to be associated with increasing cholesterol or with increasing bad (LDL) cholesterol, from what we can tell, so far. Of course, any fat is highly caloric, and cocoa butter is no exception. Most of us should cut down on our total calorie intake, so if you eat a lot of "good fats" from plants, cut down on calories from other sources.  A little bit of fat can't hurt if it is "good fat". Cocoa butter doesn't seem like a bad fat to have. And we all need some "good fat" triglycerides in our diet.

Of course, if you apply cocoa butter to your skin, it makes a great moisturizing agent (as most triglycerides will!) and it would be utterly absurd to think that any negligible, trace amounts of caffeine could be capable of penetrating your skin to become systemic.

Second, it isn’t at all clear whether caffeine is bad for pregnant women, but a few observational studies show that only a fraction of women drinking more than 3 cups of coffee daily (in other words, an obviously jittery amount of caffeine) might have a problem. So pregnant women should cut back on their caffeine consumption. I have never seen any study suggests that they should avoid caffeine completely.

This is the only precaution concerning caffeine that has really caught my attention, other than the obvious milder side effects like insomnia, nervousness, and an inordinately frequent longings to pee, assuming too much caffeine is consumed.

This precaution does not surprise me, since too much of anything is usually bad for you. This is the first rule you learn in toxicology. You can die from drinking too much water, but it is really hard to do, for example.

When taken in moderate amounts, caffeine is associated with health benefits: decreased risk of Parkinson’s disease, decreased risk of suicide, and fewer gall bladder problems. Plus, the drinks in which caffeine occurs (coffee, tea, and chocolate) also contain significant doses of antioxidant polyphenols and flavonoids, which can be obtained in decaffeinated versions of tea and coffee if you don’t care for how caffeine makes you feel.

Earlier studies with caffeine were "confounded"; that is, researchers made the mistake of not worrying about other variables in an observational study. This is a potential problem with any sort of observational study, but it can be statistically controlled for if the researchers are prudent enough to worry about doing so. For example, former studies included people who both smoked and consumed caffeine, and the effects of smoking, which we know are bad, were not statistically edited out, so to speak, so the data was misleading.

Other studies involving animals can be suspect if tons of caffeine or any substance, indeed is used, because we know that the more you expose any animal to any particular substance, the more likely that substance will do harm. So you have to look at the doses in those studies and be more cautious about concluding a harmful effect, unless relatively small doses were used. For example, those famous studies of saccharin showing bladder cancer in rats used ridiculous megadoses of saccharin that no human would realistically take. (So I keep all my saccarin on the top shelf of my kitchen--where the rats can't get it.)

Cocoa beans are processed to provide two main products:

1. cocoa solids, also called cocoa liquor (although it has no alcohol). This is what we use as cocoa powder. This part has all the flavor of chocolate and contains caffeine. However, cocoa solids contain much less caffeine than coffee.
2. cocoa butter, which is the fat obtained from the bean. It is almost entirely triglycerides (what people call “fat”). Caffeine is not a triglyceride; it is in a different chemical class called a methylxanthine. There is no caffeine in cocoa butter. White chocolate, which is made from cocoa butter without the dark cocoa solids, therefore contains no caffeine, either.

To read more about cocoa constituents, see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6396642&query_hl=3&itool=pubmed_docsum

Here is a comprehensive review article with probably more information than most people would ever want to know on the disputed association between excess caffeine and still born pregnancies:

http://www.scielo.br/pdf/csp/v21n6/04.pdf

Which basically restates this old abstract:

Nutr Rev. 1996 Jul;54(7):203-7.

The effect of caffeine on pregnancy outcome variables.

Hinds TS, West WL, Knight EM, Harland BF.

Center for Drug Abuse Research, Howard University, Washington, DC, USA.

The American public consumes a wide array of caffeinated products as coffee, tea, chocolate, cola beverages, and caffeine-containing medication. Therefore, it seems of value to inform both the scientific community and the consumer about the potential effects of excessive caffeine consumption, particularly by pregnant women. The results of this literature review suggest that heavy caffeine use (> or = 300 mg per day) during pregnancy is associated with small reductions in infant birth weight that may be especially detrimental to premature or low-birth-weight infants. Some researchers also document an increased risk of spontaneous abortion associated with caffeine consumption prior to and during pregnancy. However, overwhelming evidence indicates that caffeine is not a human teratogen, and that caffeine appears to have no effect on preterm labor and delivery. More research is needed before unambiguous statements about the effects of caffeine on pregnancy outcome variables can be made.

I hope that helps!

Holly

This is your brain on rosemary

Holly,

I am sitting here with your book, borrowed from the Aiken Public Library in South Carolina, and I am delighted!  For years, I wondered why no one wrote something like that.  I found your website, read your bio, and all I can say is thanks again.

I taught high school for almost 30 years, and always hoped I could inspire even a few of my students to do good work. I'm sure you inspire hundreds.

I have one question: why do I love the smell and taste of rosemary so much?  In the 70's, in Pennsylvania, I started a vegetable garden out back and didn't even know what rosemary was when I planted it.  But I always felt it must have something special to it.

Again, thanks, for a great book!

Dennis

Hi Dennis,

Did you know that rosemary can get into your brain after you smell it?

But first let me say that your message meant a lot to me, especially since you have also been a teacher, so you must know how challenging it can be to communicate ideas. Thank you so much!

This is the first book that I have written, so I had no idea what to expect. Already it seems to be gaining more notice than I would have expected, and I am deeply grateful. And thanks for supporting your local library--our libraries are so often forgotten but always in need.

About your affection for rosemary, who can say why it makes your brain so happy? Do you have a childhood association with the herb? Sometimes our brains link a particular fragrance to a vivid memory, and the smell always evokes that particular memory. I can't smell roses without thinking of my grandmother, who used rose oil liberally.

I can relate: You may have an affection for rosemary, but I know I get more happy than I have any right to get, every time I smell fresh basil. Perhaps this is because every time I bring basil into our kitchen, it signals a time of celebration, since my fiance and I have transformed pesto making into a household ritual signaling celebration.

In researching some of the nicer smelling herbs, like lavender and lemon balm, I was intrigued to learn that some of the small fragrant molecules, called monoterpenes, can get into your brain after you inhale them!

The reason that this impressed me is because this is not an easy thing to do for your average molecule. If you ingest molecules, most can not penetrate your "blood brain barrier", a barrier that chemically isolates the brain and spinal cord.  This barrier is for the best, really, since you don't want any old foreign molecule potentially messing with your precious brain.

But many of those small, smelly monoterpenes from plant essential oils can penetrate the blood brain barrier, which is better at preventing water-soluble molecules from penetrating it than small oily ones. Some of the monoterpenes from lemon balm enhance the action of GABA (gamma-aminobutyric acid) in the brain, which slows your brain down. So the aromatherapists could be on to something.

"Rosemary for remembrance", Shakespeare wrote in Hamlet, but now we might add, "Rosemary for cerebral blood flow". The monoterpenes from rosemary include cineole, borneol, camphor, and pinenes, which give it its pungent, piney smell. One study using brain magnetic resonance imaging show that after people inhale cineole, cerebral blood flow increases. Rats sniffing borneol had increased hypothalamic levels of serotonin and histamine. Histamine plays a major role in wakefulness in the brain. (That's why certain antihistamines make you sleepy.) So the common subjective perception of rosemary as "stimulating" could have a biochemical basis after all.

Lastly, I can't resist mentioning one of my favorite and more amusing myths concerning rosemary. If rosemary thrives in a woman's garden, that woman supposedly dominates in caring over the household. I have to confess I'm secretly pleased that my own indoor rosemary thrives, and when I mention this to my fiance, he smoothly asks for the location of this offending herb so that he might do something about the situation. I tell him I forget where it is.