Ask Me How it Works

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!      

 

Does alcohol affect lactose digestion?

 

          Hey Holly,

From what I understand, lactose intolerance is your body's inability to break down milk sugars.  Is this compounded by drinking alcohol?

While doing research for a Psych. paper on caffeine I stumbled onto your site (the page on Guarana).  I'm also taking a pre-chem course; going back to school to learn more about nutrition and Biochem.  As a beginner, I find complexity of the subject daunting and I'm not sure if I'll finish the major.

I just wanted to say that I like your easy-to-understand approach and find your passion and integrity inspiring!  I own Harold McGee's "On Food and Cooking" but, for now, it's a bit dense.  I'm going to buy your book and I feel renewed to learn and dig in deeper!

Keep up the good work,
R.W.


Hi R.W.,

Thanks for the kind words about my book! About the chemistry learning, take it one step at a time, and my trick (which I still use!) is to STOP reading every time I come across a word or idea I am unfamiliar with. Then, I look it up in numerous sources, until I am more comfortable with it, and go back to reading the text. Even words as simple as "molecule" and "atom" get confused by my (gasp) graduate students.

It's crucially important to be familiar with the most simple definitions of things and have a clear picture of them in your head. Especially since you can't see a lot of chemical things with your eyes (they are too small!) you have to use your imagination a lot.

I also tend to write down notes of things I want to learn. Even if I never read my own notes, ever, the act of writing it down helps cement it in your brain.

Finally, be patient with yourself, and realize it takes a lot of practice to imagine this real world of small molecular objects moving around and doing things.

About the lactose intolerance question--I have never heard of alcohol influencing the condition, one way or the other. I also can't think of a mechanism by which alcohol would affect the digestion of lactose. In lactose intolerance, you don't have enough lactASE, the enzyme that turns lactose into the digestible sugars glucose and galactose. The lactose remains in the gut, attracting water, and the water must leave along with the lactose out the bitter end. Not so nice!

Feel free to ask more questions as you go along. In the back of my book I have a big section on chemistry and biochemistry, which might help chemistry or biochemistry students--I hope someone reads it and finds it useful, anyway. I never know if anyone looks at my appendix!

All the best!
Holly      

"Real Food" Vitamins Versus Synthetic OTC Vitamins

Hi Holly,

Does taking a "real food" prenatal vitamin vs. a synthetic over-the-counter or prescription really make a big difference?

Thanks!

Newly pregnant

Hi Newly,
First of all, congratulations!

Second, no, the "Real Food" vitamins are a Real Marketing Gimmick. And they are Real Expensive. You can get Real Foods by eating Real Foods. Yes! Eat lots of plants! Lots and lots of plants. They are so much more delicious than pills. And the amount of protective plant chemicals in them will far outweigh the relatively tiny amounts in the "real food" pills.

I do think it's a good idea, nonetheless, to take an inexpensive, mostly synthetic vitamin. Let me explain what I mean by synthetic. These are made in a lab, thus they are usually cheaper. They are "natural" since they are made by animals. People are animals! OK, "Natural" actually has no legal meaning on labels and is used as a marketing ploy. The anachronistic, philosophical separation of "Man" and "Nature" is not scientific, it does not help inform us of the therapeutic value of compounds, and it provides a rationale for us to damage what we perceive of as separate from us--"nature"--but I am always trying to convince people that we are part of nature.

Synthetic vitamins are identical to ones isolated from plants--I have been convinced of this, personally, since countless tests for over the past 100 years have verified this without the slightest deviation in results. Anyone trying to tell you differently is trying to sell you something.

However, there are some vitamins that are difficult, technically, for chemists to make. Plants are such admirable chemists! So look for one with "natural" (in this case that means plant-derived) vitamin E, or for synthetic D- or alpha-tocopherol. If it says "DL tocopherol", that means a chemical impurity, L-tocopherol, which isn't known to be harmful, but is just an unknown, was not separated in the lab from the active from of the vitamin. That is less desirable, to have an unknown in there. So an inexpensive vitamin which is mostly synthetic but could have some "natural" plant isolated vitamins seems like a good bet.

Many people fall short of a few key vitamins, and taking a cheap multi helps make up the difference. For example, if you are a strict vegan, you ought to take a B12 supplement to avoid pernicious anemia, and older people have trouble absorbing B12, too. I have a vegan friend who was chronically tired and had incipient nerve damage, but he is now getting better after I reminded him to take his B12.

However, you can harm yourself by getting too much of certain vitamins. Since there are so many vitamins and minerals, and so many different brands, it can get confusing fast! For an excellent review of what to look for (and what to avoid) in a multi, check out this excellent review of multis by the Center For Science in the Public Interest.

Also, consumerlab has a wonderful site that you have to subscribe to for a small yearly fee, but they independently test many brands of supplements and vitamins and make sure they contain what they say they contain, and that they have no naughty thing in them like heavy metals or unlisted drugs. You would be surprised how many supplement makers have been caught by consumerlab with inadequate amounts of what you think you are buying, or icky things in them. But the supplement and vitamin business is not regulated, so we as consumers must remain vigilant by first investigating whatever we plan to take.

In addition to a multi, women should take at least a gram of calcium per day (1000 mg) AND vitamin D (since you need the D to keep absorb the calcium). A single multi pill is too small to contain a whole gram of calcium. And there's lots of talk now about increasing the RDA for D lately, so keep your ears perked for that. I'm currently winning a battle against osteoporosis with weight lifting, calcium citrate, and extra vitamin D, but it's a tough battle even with all my efforts, so I'm currently annoying all my female friends by telling them to take their calcium plus D.

Now, you are in an extra special position, having two to worry about, so you have probably heard all this before, but you will have to watch out for eating too much of the wrong sorts of fish, that would give your baby too much mercury. You can read about this, again, from the Center for Science in the Public Interest.

Also, of course, it's best not to drink alcohol while pregnant, at all! This will mess with your baby's development. When everyone else is drinking around me and I don't want to, I find a non-alcoholic beer, sparkling water, or some lovely tea just as satisfying. And then I'm more likely to win whatever silly board game we tend to be playing.

Also, if you are pregnant and have a cat, get someone else to scoop the litter to avoid toxoplasmosis, or use gloves and then wash your hands throroughly afterwards if you can't. This is my daily task and I recommend making it more exciting by humming a few bars of the National Geographic theme song and pretending I am on an archeological dig. What will we find today? Lost pharaoh's treasure? Crumbling Mayan ruins?

Best of all, get regular check ups through your pregnancy with a doctor that you trust, who can probably think of more things to add to my short list of what to do and what not to do.

Best wishes to both of you!
Holly

Join me at the Bailey's Harbor Autumnfest in Door County, WI, Sept. 15!

If you would like to say hi to me, quiz me on my book (I'll bring my favorite, back-up references!) or just have me sign your copy, come by one of my favorite bookstores in one of my favorite towns!

I'll be at Novel Ideas in Bailey's Harbor, in Door County, WI, Sept. 15!

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

We did the Fandango!

We are back in Marin County, from the Florida fandango! I gave talks on the chemistry of tea, and in doing so, it made me want to drink a lot more tea.

I met the incredible Kim Pham of the Kaleisia tea lounge, who is a little dynamo of good energy, supporting talks for scientists and herbalists, bringing the community together, and creating many philanthropic projects. I don't know how she does it all. Please suppport her in any way that you can...you can buy some tea off her website.
We had a great time, met a lot of fascinating people, and will be sure to return next year!

Here Tim and I are clowning around at the Museum of Science and Industry in Tampa:

Join me for the Florida Fandango March 10 in Tampa

You can see me in person at the Florida Fandango March 10th.

Bring your questions, and I will do my very best to answer them, or at least show you how anyone can use some my favorite resources to gather high quality data on your question.

You can also see me at the Kaleisia Tea Lounge in Tampa, where you can sign up for a workshop on the chemistry of tea.

Warmest Regards,
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!

Exotic juices "taste like money"

That is the opinion of the Center For Science in the Public Interest, joining a consensus of opinions from all of my most trusted sources.

It's not that juice is isn't healthy! It just shouldn't be so expensive, and it isn't going to perform miracles all by itself.

Lately, many have asked me about these exotic juices that are supposed to cure cancer, diabetes, fill in the blank...

It seems to me that what they all have in common is that they are all absurdly expensive, and were all once consumed ages ago by mysterious races of exotic people who are now all dead. These juices include acai, noni, mangosteen, and pomegranate, and there are probably others that I'm forgetting here.

OK, I hate always being such a downer! I hate telling people to not get excited over highly marketed health products! I am no fun at all! I wish I could be more fun.

If I wanted to be really popular and make lots of money like the convicted con artist Kevin Trudeau, I would just act like him, and tell everyone that every plant-derived product is wonderful, and that there is a conspiracy of doctors (who mysteriously never get cancer and their families never get sick?) withholding all this fantastic information from you. You'd be surprised how many people like hearing that, based on his book sales. Then I would be more popular and sell lots of books and make lots of money. Isn't that ironic? That's what I get for not being fun.

But I value truth more than I value being popular, and I am doing just fine, money-wise, anyway. I have this idealistic notion that, even for data that we don't like, data that conflicts with what we want, it may be that the real truth is more interesting and beautiful than our previous conceptions might allow. So we have to give up what we want, a lot, in science, and re-evaluate. That is why I think we need to take a hard look at unpromising products and deal with the data honestly. We just might learn something even more wonderful than we could have imagined in the first place.

Well, I have to say that juice isn't bad, it can even be very healthful! But it doesn't have to be exotic, and it certainly should not be expensive. Why not buy whatever locally made, inexpensive juice turns you on the most? If you really like it, chances are higher that you will actually drink it.

If it is really sweet, watch out for calories and sugar, that will not help with diabetes, now, and the natural sugars in the juice will turn into triglycerides (fat), which will make you fat! I had to laugh, when researching grape products for my book, over how many old references recommended the use of grape juice to "fatten up" a thin person. That advice is now sadly antiquated, but I am sure it was advice that worked. So keep it in moderation!

But I will say that many juices, especially some of the darker colored ones with those interesting plant pigments in them, certainly are healthy--in moderation. These reddish-purple anthocyanidins and their polymers (oligomeric proanthocyanidins, or "PCO"'s, "OPC"'s and an inordininate number of other synonyms) in particular may benefit our vasculature.

I know everyone is going on and on in the news lately about resveratrol from fermented red grape skins these days, and it is exciting stuff--in a test tube. But not in people, sad to say! That's too bad, because when resveratrol is dumped upon yeast, worms, and fruit flies, it turns on a life prolonging gene called SIR2, associated with the life prolonging effects of caloric restriction. Whether or not it can do the same for a calorically unrestrained person remains to be seen.

Another problem with resveratrol is that what little resveratrol that does get through the intestinal lining is quickly metabolized into other molecules. That sucker just does not get absorbed very easily. I have optimistically speculated in my book about how trace resveratrol metabolites might, having a similar structure, have similar activities to resveratrol in the exciting test tube studies, but again, that is a big if, and it hasn't been tested. Those metabolites are pretty short lived, so they are hard to do studies on.

But a recent Nature article suggests that it may not be the resveratrol from wine, but these OPCs, that are contributing to the heart benefits of moderate red wine drinking.

If so, that's good news for people who drink other red juices, that often contain either OPCs, or similar molecules, and their chemical precursors, the anthocyanidins.

What is perplexing is that these PCOs are pretty large molecules, and they also stick to proteins in our gut, so you might think we have trouble absorbing them. I think we do have trouble absorbing them. But some of the smaller ones may slip through the intestinal lining into the blood (simulated gut lining tests suggest this is so). What is nice about them in our blood stream is that they seem to have a relaxing effect on blood vessels and blood pressure, according to several studies. They may also stick to bacteria and prevent the bacteria from doing us some harm, perhaps. That last OPC trick relates to the famous use of cranberry juice to prevent urinary tract infections, and recent data suggest cranberry could assist in preventing attacks of bugs that cause foodborne illness. (Of course, I wouldn't substitute it for washing everything thoroughly!)

When I am living in Wisconsin (I move around a lot) I like the local cherry juice, which is abundant there. But it's cheap and easy to get when I live there. Instead of trying for pricey, grass-is always-greener juices from distant exotic places, why not look around you and support your local farmers?

Yes, juices can be very healthy! But are they cures for all sorts of diseases? What do you think?

Even my dad (an engineer) just wrote me, this morning, from Florida:

Hi Holly,
Just got back from our class at the Unity church. I picked up a flier that talks about the berry acai berry that has destroyed cultured human cancer cells in a recent Univ. of Florida study, one of the first to investigate the fruit's puported benefits. Published Jan 12th in the Journal of Agricultural and Food Chemistry, the study showed extracts from acai berries triggered a self-destruct response in up to 86% of leukemia cells tested.

I can mail the one page to you or fax it. Our fax is the same as the house phone.

Love dad, gotta go do eng'g work...ugh

And this is what I wrote back:

Hi dad!
Don't believe the expensive exotic berry juice stuff. I have read a lot about that, lately, and these are examples of popular marketing schemes (also with mangosteen juice and noni juice, and others) that have made millions but have very little good data to support them.

For example, you put berry juice, or spit, or coffee, or tea, or dirt or (fill in the blank!) in any bunch of cells in culture (like cancer cells) and-oh my god-they die. No kidding. When I worked in the lab my cultured liver cells would just die if I sneezed on the dish they were growing in. What a pain. Cells are easy to kill, in a dish, even cancer cells.

It isn't a cure for cancer. Show me some tests with actual people who have cancer, and I am talking double blind placebo controlled tests, not testimonials. Then I will be interested.

Love, H

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!

Could rooibos help lupus pain?

From
"lucylupus":

could rooibos help lupus pains like yerba mate did ?
is rooibos in your book ?
 in 7 years of yerba mate in the morning i never even needed 1 aspirin .
10 days without yerba mate the pain is draining me away.

i am so grateful to ask you this right now.

Hi Lucy!
I am so sorry you have lupus. I don't know why you find that yerba mate helps it, I have not seen any studies on that. They have not been done.

Perhaps antioxidants from the tea have an antiinflammatory effect? I don't know! That is just a wild guess on my part.

The only concern about yerba mate, is that there is some association of people who drink it for a long time, and esophogeal and digestive tract cancers. This is controversial, but it is something to certainly consider. Do keep getting regular check ups and tell the Dr. about that possibility of a link to cancer, so they can make sure you are OK in the that regard.

The caffeine that is in yerba mate is not a problem, despite what people may tell you. If you feel awful when withdrawing from yerba mate it may very well be caffeine withdrawal, which can feel very bad. Despite the problems with withrawal, regular, moderate caffeine intake is actually associated with several health benefits. Other caffienated drinks that also have a good dose of antioxidants are regular green or brown tea, and coffee. They might make you feel better, too.

I wish I had rooibos in my book, but I ran out of time before my publishing deadline! In the next edition I want to include more herbs, including rooibos or "red bush tea", since it has become so popular. But there are hardly any good scientific studies on it. The good news is that rooibos is not known to have any obvious negative effects, so you should have as much as you like. It has no caffeine, and since it is not made with the tea plant (Camellia sinensis) it is considered "herbal" tea. Rooibos does contain some good antioxidants. 

For lupus, there is some evidence that taking flaxseeds might help, and also vegetables in the broccoli family: broccoli, cabbage, and brussel sprouts, that is. Both contain agents (lignans in flaxseeds and indole-3-carbinol in the cruciferous vegetables) that switch estrogen into a less active form of estrogen, and estrogen is thought to play a role in the symptoms of lupus. So some researchers theorize that flaxseeds and cruciferous vegetables in the diet might help people with lupus.

Good luck and I hope that helps!

Internal arnica?

Hi Holly,

You say that Arnica should not be taken internally but I was recommended
by my doctor to take it in pill form before having rhinoplasty. I got
the 6c strength and have to take 5 twice a day.

Thanks!

Hi Alisa!

Indeed, while many herbs are safe, arnica is not one of them. People taking it internally have died. But what you are taking does not contain any arnica, because the "c" indicates it is a homeopathic remedy. So at least it won't hurt you.

Homeopaths believe that you can dilute an herb to the point of nonexistence in their preparations. They believe the water contains the "memory" of what was once in it. This is an 18th century mystical belief that has never been proven by any scientific study, although scientists have tried to proove it and failed repeatedly. One French study published in Nature, where even the editors took the unusual precaution of saying they did not believe it but wanted people to try to at least duplicate the experiment, suggested that something might be going on, but the researchers were later found to have thrown out all the evidence that did not support their theory--they just said it was "bad data", although there was nothing really wrong with it. In science, you aren't allowed to throw out data that doesn't agree with your pet conclusion. That is called "data selection", and if you do it knowingly, it is a type of fraud.

Nonetheless, a lot of people still cite this work as evidence for homeopathy.

You would have to drink a volume of the solution as large as the planet Earth to get one molecule of arnica, so you don't have to worry about any arnica in your preparation. For this reason, I don't personally recommend homeopathic remedies, even though they are very popular.

I hope that helps clear things up!
Holly

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.

Everything that I Know About Calendula So Far

I was recently delighted to hear from an editor who works for Martha Stewart Living. She was writing an article on using the herb calendula as a topical treatment.

Not having any celestial source of knowledge, I did my usual thing and dug into all the published peer reviewed articles that I could find on the topic. I found the herb quite interesting, and am inspired to write an article of my own. Here are some of the tidbits that I learned and shared with this editor:

Botany and Culinary:

Calendula is related to marigold, and sometimes called “pot marigold”, but the marigold that most people plant in their gardens is not calendula. It is related to it; in the same family (Asteraceae, also called Compositae) but not the same genus (the genus of the marigold is Tagetes and that of calendula is Calendula).

Calendula grows very easily and has bright yellow or orange daisy-like flowers. (I once had some completely invade my garden here in Utah, it took me a day to pull them all out of my garden.)

Calendula flower petals are edible, sometimes tossed in salads for color.

Laying chickens are sometimes fed calendula flower petals along with their feed, which turns the yolks a brighter yellow from the carotenoid pigments in the flowers.

Some researchers are investigating the use of calendula extracts to kill snails that carry parasites in developing countries.

Safety: Although calendula seems generally pretty safe, there is insufficient information to recommend taking large amounts of it orally on a regular basis. A few petals here and there in salads on occasion, for example, is unlikely to hurt you. Pregnant or lactating women should avoid consuming it therapeutically simply because it is an unknown. It is in a family of plants that always raises a red flag for allergies. People with allergies to other plants in this family (ragweed, daisies, dandelion, sunflower, chrysanthemums, arnica, and other daisy-shaped flowers) are more likely to have an allergy to calendula, or to eventually develop one. People in this category should perform a patch test if they want to try calendula topically, and should avoid eating it.

Nonetheless, reports of allergies to calendula are uncommon in the scientific literature, compared to allergies of other asteraceae plants. There is one published report, from Russia, of a woman who gargled with a preparation of calendula and she suffered anaphylaxis, a severe allergic reaction:

Klin Med (Mosk). 1974 Apr;52(4):142-3.

Title: [Anaphylactic shock after gargling with an infusion of Calendula]

[Article in Russian]

Gol'dman II.

Publication Types:

Case Reports

Another study showed that after 433 patients were patch tested for calendula allergy, 9 responded positively, showing they had the potential for a bad reaction to calendula:

Contact Dermatitis. 2001 Nov;45(5):269-72. 

Title: The seamy side of natural medicines: contact sensitization to arnica (Arnica montana L.) and marigold (Calendula officinalis L.).

Reider N, Komericki P, Hausen BM, Fritsch P, Aberer W.

Department of Dermatology and Venereology, University of Innsbruck, Austria.

Animal tests show calendula is relatively nontoxic. Cell and animal studies show nothing alarming, but more studies should be done. Because studies are incomplete, a 2001 report prudently says “it is concluded that the available data are insufficient to support the safety of these ingredients in cosmetic formulations.” (This is not surprising since it is the status of all but the most thoroughly studied herbs.) At that time is was judged to be used in around 200 different cosmetic products.

Title:Final report on the safety assessment of Calendula officinalis extract and Calendula officinalis.

Int J Toxicol. 2001;20 Suppl 2:13-20. Review.

Homeopathic calendula: Homeopathic preparations of calendula (not to be confused with naturopathic or holistic) involve a particular method of diluting the herb down to nonexistence in the preparation. Homeopaths believe the preparation retains a “memory” of what was once it, which is really rather bizarre when you think about it. This has never been proven by any experiment, though people have repeatedly tried to prove it. There is no evidence that homeopathic remedies in general work any better than a placebo, although they have been repeatedly tested. (They can work by the placebo effect, which sometimes is impressive however.) Nonetheless, for this reason, I would never use or recommend a homeopathic preparation—I would prefer one that has actual calendula in it.

Formulation: Most of the folkloric and scientific use of calendula involves the use of the outer ray flowers. Each flower has many tiny “disk” flowers, as well, in the center of the flower, but these are not usually used, nor is the green part of the herb. Curiously, we now know that the ray flowers have the highest percentage of faradiol (farrah DIE-all) esters, which are thought to be antiinflammatory, and that could explain how they help skin to heal. (The faradiol esters were 10 percent higher in ray flowers than disk flowers, and 100 percent higher than the green bits.)

Zitterl-Eglseer K, Reznicek G, Jurenitsch J, Novak J, Zitterl W, Franz C. 

Title: Morphogenetic variability of faradiol monoesters in marigold Calendula officinalis L.

Phytochem Anal. 2001 May-Jun;12(3):199-201.

Also, the faradiol esters are oil-soluble, and not water or alcohol soluble. So the best method of obtaining them is to soak the outer flowers in something oily like vegetable oil, or petroleum jelly.

Faradiol esters are also found in sunflower petals, arnica petals, coltsfoot flowers, and dandelion herb. Arnica, however, often causes a rash, and the other plants are less well known.

The oil-based preparations will end up being colored, since carotenoid pigments that are colored are oil-soluble and will leach out from the flower petals into the oil. Carotenoids in moderate doses are known to be antioxidant and protective. (Megadoses of oral carotenoids may be harmful, though. Most megadoses of antioxidants end up being more harmful than helpful, unfortunately. I can talk about why that is, if you like, on your radio show...)

Water or alcohol preparations are less likely to contain the above faradiol esters and carotenoids, but more likely to contain common plant flavonoids, which are not unique to calendula but found in most plants. Flavonoids often act as protective antioxidants by a variety of different mechanisms, and may in theory have anti-cancer activity.

Faradiol esters’ activity: Faradiol esters in an a category of common plant molecules known as triterpenes (try-TERP-enes). Faradiol esters are “antiedemic” (relieve localized swelling of tissues) and antiinflammatory in a small number of animal studies. It is possible that other triterpenes in calendula have similar, but perhaps less potent, activities. Antiinflammatories in general relieve “heat, pain, redness and swelling”—the four common signs of acute (short term) inflammation. They can also speed healing. Inflammation is caused by the immune system over-reacting and causing damage. It is a case of friendly fire. Inflammation also commonly underlies, and we now think, perpetuates many disease processes. So it often helps to shut it off.

This study singled out the faradiol esters as the most active antiinflammatory agents in calendula flowers:

Planta Med. 1994 Dec;60(6):516-20. Title: The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers.

Della Loggia R, Tubaro A, Sosa S, Becker H, Saar S, Isaac O.

Istituto di Farmacologia e Farmacognosia, Universita di Trieste, Italy.

In the following study the faradiol esters from calendula were found effective in reducing the swelling of mouse ears that were treated with an irritant. A compound derived from calendula’s faradiol esters, called faradiol, was just as effective as indomethacin, a prescription antiinflammatory medicine which is similar to ibuprofen. J Ethnopharmacol. 1997 Jul;57(2):139-44.

Title: Anti-oedematous activities of the main triterpendiol esters of marigold (Calendula officinalis L.).

Zitterl-Eglseer K, Sosa S, Jurenitsch J, Schubert-Zsilavecz M, Della Loggia R, Tubaro A, Bertoldi M, Franz C.

Institute for Botany and Food Science, University of Veterinary Medicine Vienna, Wien, Austria.

Freeze-dried calendula extracts protected mice from the inflammatory effects of injections of carageenan and prostaglandin E1 in another study. White blood cells normally infiltrate the site of injection, causing swelling, but calendula prevented this from happening.

Vet Med Nauki. 1981;18(6):87-94.

Title: [Anti-inflammatory action of a group of plant extracts]

[Article in Bulgarian]

Shipochliev T, Dimitrov A, Aleksandrova E.

Another Bulgarian study showed that calendula extracts sped wound healing in rats:

Acta Physiol Pharmacol Bulg. 1982;8(4):63-7. Title: Influence of the physiological regeneration and epithelialization using fractions isolated from Calendula officinalis.

Klouchek-Popova E, Popov A, Pavlova N, Krusteva S.

Inflammation caused by an irritating chemical placed on mouse ears was relieved markedly by calendula extracts:

Phytochemistry. 1996 Dec;43(6):1255-60. 

Title: Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects.

Akihisa T, Yasukawa K, Oinuma H, Kasahara Y, Yamanouchi S, Takido M, Kumaki K, Tamura T.College of Science and Technology, Nihon University, Tokyo, Japan.

How does it work? This is always what I am most interested in, because some mechanisms are better than others, some are safer than others. So far, we don’t really know calendula works, because those studies have not been done.

But there is a hint that water and alcoholic extracts of calendula do not work like aspirin and other related (NSAID) drugs. These drugs prevent an enzyme (cyclooxygenase or “COX”) from making prostaglandins, and some prostaglandins are known to promote inflammation. Calendula and a number of other herbs were tested for this aspirin like-activity (tested for COX inhibition). Calendula was not singled out in the article for COX inhibition as other herbs were, so it doesn’t seem to work that way. However this study used alcohol and water extracts and these extracts do not contain the faradiol esters, so they don’t say anything about how the faradiol esters might work. It might still be that faradiol esters act like aspirin (but their structure is not very aspirin-like so I personally doubt that.)

Roum Arch Microbiol Immunol. 2003 Jan-Jun;62(1-2):117-29.

Title: Hydroalcoholic plant extracts with anti-inflammatory activity.

Herold A, Cremer L, Calugaru A, Tamas V, Ionescu F, Manea S, Szegli G.

National Institute of Research-Developmentfor Microbiology and Immunology Cantacuzino, Bucharest, Romania.

Looking at the structure of faradiol esters, they look very steroid-y to me, that is, they look like steroids. Steriods can be either hormonal, or inflammatory, in general. Some steroids have activities both of hormones and anti-inflammatories. We don’t know if calendula has any hormonal activity, those studies have not been done.

One of the most well-known steroidal antiinflammatories is hydrocortisone cream, or cortisol. In theory, faradiol esters might act like hydrocortisone, because they resemble hydrocortisone, but that is not known, the studies have not been done. Hydrocortisone and other antiinflammatory steroids work by preventing the precursor to prostaglandins (called arachidonic acid) from getting released from cell membranes. Aspirin-like drugs, on the other hand, prevent this arachidonic acid from being turned into prostaglandins by the enzyme cyclooxygenase (“COX”).

Clinical studies with actual people: These are always so much nicer, for so many reasons, than animal studies. There is only one well-designed one. This is a French study comparing oil-based calendula extracts to trolamine, published in the Journal of Clinical Oncology.

The punchline is that women using calendula (126 women) had statistically significantly less acute dermatitis than those using (128 women) trolamine (trade name Biafine). The dermatitis that radiation therapy causes is similar to sunburn, but can be more severe, with red skin, peeling, and blisters forming. The women using calendula also had less pain and this effect was also statistically significant. What I thought exciting about the study was that the women using calendula were more likely to continue radiation therapy without interruption, which is more likely to get rid of their cancer.  Patients in the trolamine group requested 12 total suspensions of radiotherapy treatments because of dermatitis, but only 1 patient in the calendula group requested an interruption in her therapy, and that request was not related to her dermatitis.

J Clin Oncol. 2004 Apr 15;22(8):1447-53.

Title: Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer.

Pommier P, Gomez F, Sunyach MP, D'Hombres A, Carrie C, Montbarbon X.

Department of Radiation Oncology, Centre Leon Berard, 28 rue Laennec, 69373 Lyon Cedex 08, France.

You can read the article yourself if you want, if you link to http://www.jco.org/cgi/reprint/22/8/1447

The authors of the study are up front, which is nice, about a couple of limitations of their study. First, they did not compare calendula to an inactive placebo, which would be more ideal so we could see just how effective calendula is. But it perhaps it would have not been kind to give half of the women an ineffective skin treatment after their breasts were burned with radiation. Trolamine is often used on skin after it has been treated with lasers or radiation therapy. It actually is not thought to be all that effective, so in that respect it may have acted somewhat like a placebo.

Another limitation of their study was that it was single blind, not double blind. Ideally, you want neither the subjects nor the scientists to see who is getting what, so no one can subjectively form any preconceived bias for a particular treatment. But the calendula ointment is yellow, so it was impossible to disguise it from the patients. So they knew what treatment they were getting. The doctors, on the other hand, did not know who got what treatment, since the patients could were required apply their ointments many hours before their skin was examined by the doctors, and by that time their skin was not yellow.

The article mentions several times, by the way, that 30% of the women using calendula did not like applying it, (compared to 5% of the women using trolamine.) The article didn’t say why. Perhaps they did not like putting something so yellow on their skin, or perhaps the tactile sensation of the ointment was unpleasant. Trolamine did not have such a problem with compliance.

Rare and previously undiscovered carotenoids in calendula flowers: Carotenoids are a type of plant pigment that is common in plants; they are often yellow, orange, or red. They are likely anti-oxidant and free radical scavenging (that’s a good thing.) I was intrigued that three new versions of lycopene were discovered in orange, but not yellow, calendula flowers. The common form of lycopene, that we are most familiar with, is what makes tomatoes red. (These new versions have similar structure as chain-like molecules, but are “cis-trans isomers”, that is, they bend in different ways along the chain at locations of double bonds.) Orange calendula flowers also contain some carotenoids that are relatively rare in nature. We don’t know what their properties are, if any, but it is likely that they are at least similar in activity to other more common carotenoids:

Biosci Biotechnol Biochem. 2005 Nov;69(11):2122-8.

Title:Analysis of carotenoid composition in petals of calendula (Calendula officinalis L.).

Kishimoto S, Maoka T, Sumitomo K, Ohmiya A.

National Institute of Floricultural Science, Ibaraki, Japan. sanae@affrc.go.jp

Will alpha hydroxy acids work if they are pH balanced?

Dear Holly,

I have a skin question. I read recently that alpha hydroxy acids will not work if they are in a "pH balanced" formulation. Is this true? If so, how can I tell if I am spending a  lot of money for a product that won't work? Can I change their pH and make them effective?

PG.

Dear PG,

What you read is true. Alpha hydroxy acids will not be in an active (acidic) form if they are "pH balanced", or in other words, neutral, at pH 7. Some of these products are quite expensive, and I was surprised to learn that a portion of even the expensive products do have a pH which renders their effectiveness questionable.

The reason I took a while to answer your question is because I wanted to buy a number of products and test them. At work I can use a pH meter, but in my kitchen I use simple litmus paper which is readily available off the Internet to buy, and it ought to be dirt cheap. I buy mine from a local beer making supply store, and normally use it in testing wine that I make. You can get your own litmus paper and test your sample, so you can do the same. I'd get a couple of types for ranges of values below 7 if you are testing your products.

If the opacity of the formulation is a problem, try diluting the material 1:10 in water, preferably freshly opened distilled water. (Carbon dioxide from the atmosphere dissolves into standing water and normally makes water a wee bit acidic.) The alpha hydroxy acids are water soluble and will leach out into the water. Then, the pH that you measure will be higher (more basic) than the true value by one unit, (since pH is a log scale and you diluted by ten.) So if you do dilute the material tenfold, subtract 1 from the pH that you measure. This should get you a crude estimation of the pH.

But what pH do you want?

In order for half of the alpha hydroxy acid present to be in the active, acidic form, the pH of the solution must be equal to something called the pKa of the acid. Acids have different pKa values, it is a measure of how strong they are (the lower the number the stronger they are.) If any of my three readers out there (excluding my mom) are dying to know more about pKa values you can read my review of acid base chemistry. Here are some common alpha hydroxy acids and their pka values. You can see most are around 3.

glycolic acid     3.74

lactic acid        3.08

malic acid       3.40

tartaric acid (meso form)  3.22

alpha-tartaric acid     2.98

citric acid (has three acidic regions on it, and all three have different pka values: 5.19, 4.77, and 3.15.

You could always lower the pH of your formulation and make it more acidic. Acidic solutions, by definition, contain an excess of hydrogen (H+) ions. So why not buy a bottle of hydrogen ions and add them? Well, you can't! That is because a bottle of hydrogen ions doesn't exist. Ions of like charge repel each other. The next best thing to do is add something that is not charged, which can release hydrogen ions.

An acid is something that can release hydrogen ions (or split water in two and hold onto one half of water and release the rest as a hydrogen ion.) You can always make your formulation more acidic by adding some mild acid, like a few drops of vinegar, lemon juice, citric acid, or ascorbic acid (but not ascorbate, that is a base.)  This would certainly make it more powerful. But I must really caution you about that!

Maybe there is a good reason why the company wanted only a minuscule amount of the alpha hydroxy acid to be in the active form. The acids work, scientists believe in part, by breaking down junctions (desmosomes) between dead skin cells. This allows dead cells in outer skin layers to be removed, and it does seem to stimulate growth of cells below, and their manufacture of water-attracting molecules like hyaluronic acid and reinforcing ones like collagen. But the process can be irritating, and you can end up looking worse than before, with reddened, irritated skin.

You are supposed to apply sunscreen religiously if you use such products, (actually it is a good idea to do so daily, anyway.) The more powerful preparations are applied by a dermatologist, not at home. So although it is theoretically possible to make your preparations more active, I don't advocate placing a lot of active acid on your face without a dermatologist administering them.

Finally, if anyone is wondering why the pH can render an acid effective or ineffective, here are some chemical details:

Alpha hydroxy acids are quite popular in skin formulations these days. The