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More on "Harvey’s Chocolates"

Date: May 6, 2024

Many readers wrote to me after reading the latest article on "Harvey's Chocolates". I am glad it generated such a high level of interest! Let me address some of the questions you raised.

I think I am a pretty good chemist, but a gourmet cook I am not. I would expect most of you are far better cooks than I am. Just as I used "Harvey" and the Round Headed Kid "RHK" protocol to illustrate some therapy options and the logic that may be involved in making such decisions, "Harvey's Chocolates" is a tool that I used to get across some important concepts of drug transport. A long and boring article on "first pass metabolism losses in the liver" would not have gotten as many of you interested, right? A little sugar makes the medicine go down a lot better.

Talking about sugar: some of you asked why not make the caramels with sugar substitutes. Why not indeed, if that is your preference. Use your talents, your skills and creativity, not to mention your can-do spirit, make your own version of "Harvey's Chocolates". What do you give as a Valentine's Day gift to that special some one in your life who has CLL? Something that took your energy, creativity and love, all of which are as important as the EGCG.

Why caramels, why not fudge, or hard candies like lollipops? Why not chewing gum? No reason why not. I just did not have a handle on how to make hard candy or any of the other variations. As I said, you are the boss in your own kitchen.

A few points that are important to remember, as you modify the recipe:

1. It is important that the green tea extract not be heated above 210° F. I have not seem detailed thermal stability reports of EGCG, but since tea is generally consumed by steeping in water close to its boiling point, I figured it would do fine as long as we do not exceed 212° F, the boiling point of water.
2. Drug transport in your mouth works best in the sub-lingual region (the area under your tongue). The next best option is between your gums and inner lining of your cheeks, the "buccal" region. Least effective transport of drugs into tissue happens through the hard roof of your mouth, above your tongue. In each case, the transport is more effective if the drug stays in contact with lining of your mouth, and it does not generate a huge amount of saliva which is promptly swallowed, or just plain gobbled up because it tastes too good to resist! You get my drift. Something like a cough drop or lozenge might work very well.
3. I have given the amounts of the sugar, corn syrup, condensed milk in cups as well as grams. The quantity of chocolate used is to your taste, you can use more, or you can use less. The quantity suggested in Serena's recipe is about 2+ cups. The amount of EGCG is another matter. I used grams for that because it is important to have a good idea how much EGCG you have in the finished product, therefore how much you have per piece. This goes to the heart of being prudent, not over-doing a good thing. I felt measurement in grams, on a good weigh scales, will give you a more precise read on how much EGCG there is in each piece. In the recipe Serena used 10 grams, divided into 100 pieces. That translates to 100 milligrams per piece, or one tenth of a gram per piece.

How much is too much? How much is just right?

I cannot answer that question in the sense of prescribing a dosage. As all of you know, I do not have the qualifications to do that. I strongly urge you to use caution, be prudent, and by all means check it out with your doctor. Here are some guidelines to consider:

• Several research papers describe oral consumption of 800 milligrams of EGCG (as capsules) per day by healthy volunteers, with no adverse effects. Most other studies I have seen are also in this ball-park, I have not seen any that go over 800 milligrams of EGCG per day given to human subjects. This is a lot of EGCG, and it is not something that can be sustained at this level over a long period of time, certainly not without careful medical supervision in the context of a clinical trial. Oral consumption of this amount of EGCG can put significant load on your liver, something you do not want to do. So please do be careful!
• The amount of EGCG in a cup of brewed green tea varies, depending on how it is brewed, quality of the tea etc. In general, it is about 25 milligrams of EGCG per cup.
• Oral consumption has poor efficiency of absorption of EGCG into the general blood circulation, around 5%. This too has a great deal of variability from person to person.
• Assuming 25 milligrams of EGCG per cup, and 5% efficiency of absorption, a person who drinks 10 cups per day will get 25 X 0.05 X 10, or 12.5 milligrams of EGCG.
• Mucosal absorption of EGCG through the lining of your mouth (especially if you hold it there for a good long time) is a lot more efficient than just swallowing a capsule. It too varies from person to person, but an absorption efficiency of 10-20% is not unreasonable. So, if Harvey had two of Serena's chocolate caramels, each with 100 milligrams of EGCG, then even at the lower efficiency of 10% he will get 100 X 2 X 0.10, or 20 milligrams of EGCG, a whole lot better than drinking 10 cups of green tea.

The bad news is that high purity EGCG is not commercially available to consumers right now. Hopefully Roche's "Teavigo" will get to market soon. The highest EGCG content I have seen to date (and you can check this out for yourself, may be you will find vendors I have missed) is about 50% EGCG. This is a brown powder, mix of various tea polyphenols in addition to EGCG. Quite bitter to the taste, I doubt you will be able to use 10 grams of the lower EGCG product per 1,000 grams of caramel (as in Serena's recipe) and still be able to tolerate the bitter taste. A major advantage of the high purity stuff Serena used is that it does not have a strong taste. Your option is to use less of the lower percentage EGCG green tea extract, find the level where you can live with the taste in the finished product.

Be well,

Chaya
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