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Excerpted from multiple issues of Smart Drug News and Smart Drugs II.
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Questions and Answers

Note: Initials of the subscriber/author follow each question (OTP refers to an over-the-phone question, and Anon refers to a question asked by a reader requesting anonymity). If you want us to use your full name, or if you want us to omit your initials, please state so in your correspondence. Initials following answers refer to the individual editors. WD is Ward Dean, M.D., and SWF is Steven Wm. Fowkes.

This is a very long file. You can either scroll through the file manually, or you can click on the highlighted or underlined section of the question-summaries below and jump to the exact location of that question. Hint: After jumping to a question, clicking on the “back” button of your web browser will return you to the top of this file. Our Questions and Answers page is organized as a hub with spokes to a bunch of small files. This is faster, and there are more questions answered.

Table of Questions

1. Do smart drugs interact with thyroid, premarin or anti-inflammatory medications?
2. What smart drug should I take for depression?
3. Which smart drugs are best to start with?
4.A report on smart drugs and dementia.
5. What should I do? My doctor is threatening to quit if I keep taking smart drugs.
6. Thanks for all the great advice.
7. My GHB gets sticky. Does this affect its quality or potency?
8. What are the advantages/disadvantages of generic vs name-brand Hydergine?
9. What do you think about the recent announcement that vitamin C increases DNA damage?
10. Yesterday, “large segments” of the public should take vitamin supplements.
—Today, 500 mg vitamin C causes genetic damage. Is this science or politics?

Question: How will Hydergine, piracetam and other smart drugs mix with anti-inflammatory medications, premarin and thyroid? I am 68 years old and my memory and alertness are failing rapidly.

Answer: Most smart drugs, especially the ones that you mention, will have no adverse drug interactions with the medications you are taking. However, if your memory and alertness are failing rapidly, it is possible that you have an as-yet undiagnosed illness that may be causing these changes. Too often, older people experiencing rapid mental changes are written off by their family, friends and physicians as just getting older when, in fact, it is a treatable illness which is causing these changes. Hypothyroidism is one of the most common causes of memory impairment. See the section on thyroid hormone in Smart Drugs & Nutrients. ——WD

Question: What do you suggest I take for depression. Is there anything more potent than Ginko/Cola, etc.? I would appreciate an answer. ——OB

Answer: If you are clinically depressed, you certainly should be under the care of a knowledgeble physician. There are a number of causes, and a number of potential treatments. As with smart drugs, there is no “magic bullet,” and the theraputic approach is often empirical (i.e., guesswork). First, there are the obvious causes: either environmental (i.e., situational), or medical (e.g., hypothyroidism). Often, depression is caused by a neurotransmitter deficiency lack or imbalance which can be corrected by nutritional or pharmacological manipulation. For example, if there is a deficit of the stimulatory neurotransmitter dopamine, this may be corrected by supplementation with amino acids like tyrosine or phenylalanine (up to 2,000 mg per day). On the other hand, a mild reversible monamine oxidase (MAO) inhibitor like Gerovital (see chapter in Smart Drugs & Nutrients), or a MAO type-B inhibitor like deprenyl (see SDN v1n1, v1n6) may help. Improving your sleep patterns using a chrono-regulator like melatonin may improve your sleep and increase your mental and physical energy common symptoms of depression. Finally, drug therapy with anti-depressants like prozac is sometimes required. Again, we strongly advise medical supervision of all anti-depressant therapies. ——WD

Question: Which of the smart drugs is best to start with? ——MH

Answer: This is a question we’re frequently asked. The answer is, “it depends.” Unfortunately, there is no magic bullet smart drug that works well for everyone. Nor is there any known way to test in advance who will respond best to which smart drug. Therefore, the use of smart drugs remains empirical, and the choice of which drug/substance to start with is a very individualized one. For example, many users of cognitive enhancing substances prefer to use natural (non-drug) substances. For them, the best substances to start with are 1) over-the-counter nutrients from health food stores, like dimethylaminoethanol (DMAE), Gingko biloba, or phenylalanine, or 2) preprepared combination products containing neurotransmitter precursors like choline, tyrosine, phenylalanine, pyroglutamate, etc. For those that have a cooperating knowledgeable physician, Hydergine and vasopressin may be tried initially. For those who live close to the Mexican border, or who can order from overseas pharmacies, well-tested drugs that can be highly recommended for first-time include piracetam and deprenyl. ——WD

Question: I have been giving my mother piracetam, centrophenoxine (Lucidryl), and choline for a number of years. She is 84 years old with senile dementia. Before the introduction of these smart drugs, she has suffered strokes which left her terribly agitated. She would scream and holler uncontrollably. After smart drugs, she was a totally different person. Her agitation vanished, she stopped screaming and hollering, and her IQ went up tremendously. She can now hold intelligent conversations. Don’t let anyone tell you that smart drugs don’t work. I have living proof with my dear mother. I myself use some of the smart drugs. It’s too bad the American public doesn’t realize that without the FDA’s restrictions, these wonderful medicines would be available for their benefit. Very sad. ——RO

Answer: We think it’s tragic. Thank you for sharing your experience with your mother. Your observations, while anecdotal, are encouraging and serve to illustrate that smart drugs shouldn’t be easily dismissed as useless. You may find it interesting that the pharmaceutical company Warner-Lambert is conducting studies of piracetam for the treatment of Alzheimer’s disease. Hopefully, this research will confirm your observations regarding your mother and help make piracetam available for the millions of Americans who might benefit from its use. ——TMH

Question: My family doctor is threatening to quit being my physician if I don’t quit taking smart drugs. What should I do? He’s been my doctor for most of my life.

Answer: If your doctor refuses to treat you if you are taking various nutrients and smart drugs, fire him or her and find another doctor. Whatever medical advice your doctor offers you, it is advice and subject to your considerations as a patient. Whether or not it is a violation of medical ethics for a doctor to attempt to blackmail a patient (we have heard of numerous instances with much more serious medical implications to the threatened patient), we do not think that it is a good idea to have to keep your doctor in the dark about your health program. We strongly recommend that you find a doctor you can be honest with. ——SWF

Question: Thanks for all the great nutritional and medical advice. ——OTP

Answer: You’re welcome. However, our answers are not intended to be advice but rather information. We provide this information to assist you and your physician in evaluating as many possible approaches that we think may be useful given what you tell us in your letters. Although the distinction between advice and information may seem subtle, it is fundamentally important. Advice is a professional recommendation towards a specific treatment option, and as such, it takes away some of your responsibility. Information is merely providing knowledge of a treatment option, of historical practices, of somebody else’s experiences, etc. You (and your doctor) still have the responsibility to evaluate that information within the narrow context of your health situation and your personal values (of which we are basically ignorant). As information, we stand behind what we say. But people are different. As we often say, biochemical individuality reigns supreme. It is up to you to decide whether the suggestions we make are appropriate courses of action for you. ——SWF

Question: I live in a very humid part of the country and my GHB gets clumpy and gooey. Does this affect the potency of the GHB? What is the best way to keep it dry, or at least more manageable? ——OTP

Answer: GHB is an extremely hydrophilic (water loving) substance which will absorb large amounts of water from the air if given the opportunity. Although water does not effect GHB’s potency, it will encourage molds and other microorganisms to grow. If you have a large amount of GHB, try dividing it into multiple smaller airtight containers, each of which you can use up more quickly. You can also dissolve a few-days supply of GHB in a small amount of water which can be stored in the refrigerator for several days. For instance, if you dissolve 25 grams of GHB in 25 tablespoons of water, one tablespoon of the liquid will give you approximately 1 gram of GHB. Since this liquid can mold, make only as much as you will use in a few days to a week. If you need to store it longer, try adding more water and freezing it in ice-cube trays. If you freeze 25 grams of GHB into 25 ice cubes, each will contain approximately 1 gram of GHB. Put the frozen ice cubes into a heavy duty plastic freezer bag for storage. If the GHB solution will not freeze, either turn down the temperature of your freezer or dilute the liquid with more water (250 mg per ice cube?). Salt solutions are more difficult to freeze that pure water; most GHB is actually sodium GHB (NaGHB). You can even add fruit juice instead of water to make your GHBsicles taste better! ——JRR

Question: I really enjoy your newsletter. My question concerns Hydergine. What are the advantages/disadvantages between generic and non-generic forms? The price premium for the Sandoz Hydergine is more than two times the price for generic ergoloid mesylates. I’d like to know your opinion before I make a purchase. ——TWB

Answer: In the 80s, there were a number of non-standardized formulations of ergoloid mesylates which used various proportions of the three drugs which compromise Hydergine. Since that time, however, the formulations have been standardized, and now all forms of Hydergine have the same ratio of active ingredients. The bioavailability of the generics may be slightly less (10-20%?), however, taking a bit more of the generic is still much more economical considering the substantial cost differential. I use generic Hydergine. For those for whom price is no object, I recommend Hydergine Liquid Capsules (liquid Hydergine). The liquid capsules have even higher bioavailability than the sublingual tablets (which are themselves better than the oral tablets). ——WD

Question: What do you think about this enclosed newspaper clipping of a recent announcement in the London Times that researchers have found that 500 mg dosages of vitamin C damages genes?

Answer: The study is real, but the conclusion that vitamin C is dangerous is unwarranted by the evidence presented. Of about 20 types of DNA damage that have been documented so far by scientists, only two types of DNA damage were measured. One increased while the other decreased. What does this mean? We don't know, for several reasons.

First, the increase in 8-oxoadenine levels (a marker of damage to adenine “A” nucleotides) was offset by a decrease in damage to 8-oxoguanine levels (which is a much better-researched marker of DNA damage to guanine “G” nucleotides). With offsetting trends, the net effect is not clear.

Second, DNA damage is an incredibly complicated process that is balanced by DNA repair mechanisms. According to estimates [Ames and Gold, 1991], each cell in the body can be expected to suffer approximately 10exp5 DNA-damaging events per day. For those “exponentially challenged” readers out there, that’s between 10,000 (10exp4) and 1,000,000 (10exp6) oxidative “hits” per cell per day. This suggests that DNA repair is an extremely robust and vitally important process to consider. Yet these researchers ignored it.

DNA repair enzymes slide along the DNA strand scanning for signs of damage. DNA is composed of A-T and C-G base pairs which are strung together in a double-stranded spiral called a helix. When these repair enzymes find an oxidized adenine (A) or guanine (G) nucleotide, they snip it out (the C and T bases remain intact to maintain the structural integrity of the DNA during repair) and an unoxidized (normal) adenine or guanine is put back in its place. The “snipped out” oxidized adenine and guanine are therefore markers of both DNA damage and DNA that has been repaired. Fundamentally, we are only interested in DNA damage that is not repaired. It is the unrepaired damage that is going to interfere with protein and enzyme function.

Third, we need to know the sites of damage because there are parts of DNA that do not get transcribed into proteins. These DNA sequences are either introns (which are snipped out during transcription) or initiation (control) sites which serve to activate and deactivate the transcription of “downstream” DNA. Some of these initiation sites are now known to contain iron, which provides a clear and well known mechanism by which vitamin C can damage DNA.

Vitamin C reacts with ferric iron (Fe+3, “oxidized” iron) to form ferrous iron (Fe+2, “reduced” iron). Ferrous iron reacts with hydrogen peroxide to form a hydroxyl radical, a potent oxidant and free radical. Hydroxyl radicals are not only powerful, they are extremely unselective. In other words, they tend to react with the first thing they bump into.

Scientists have known for many decades that extracted DNA has iron associated with it, but they didn’t know whether it was naturally present in native DNA or if it was an artifact of the chemical extraction process used to isolate the DNA. Now we know that the iron in DNA is there by design. It is actually imbedded in the center of the DNA double helix at certain loci (DNA sites) where it serves as an oxidation sensor to activate DNA in response to oxidative stress.

Because the iron is bulky, it distorts the outer shape of the DNA helix. This distortion depends on the oxidation state of the iron. Under reducing (non-oxidized) conditions, the iron is present in the ferrous state and the DNA helix is fairly tightly wound around the iron atom (it only bulges slightly from the iron “nugget” imbedded inside). But when the iron is oxidized to the ferric state, it opens up the DNA so that it is more easily expressed (i.e., transcribed into RNA and then into proteins). What proteins are expressed? Antioxidants! Heat shock proteins! These may include enzymes like SOD, catalase and glutathione peroxidase, plus other proteins that help mobilize and regulate the antioxidant defense system.

The ability of DNA to “sense” free radicals and oxidizing conditions in this manner is an essential aspect of our ability to maintain homeostasis (biological stability) and adapt to stress (environmental change). The fact that there may be temporary damage to DNA is a trivial price to pay for enhanced adaptability and increased survival.

Although much of the research into iron-DNA mechanisms is very recent, we do have some idea how DNA interacts with iron. In its activated state, the ferrous iron-DNA complex can react with vitamin C and hydrogen peroxide to produce a hydroxyl radical which can (and apparently often does) attack the DNA at the iron-binding site. Remember, hydroxyl radicals are highly unselective and tend to react with the first thing they hit. Since the iron-binding site is especially rich in A-T base pairs, it makes perfect sense that more damage would occur to A and T residues than C and G residues. In fact, I would be quite surprised if the researchers at the University of Leicester did not know about the iron sites and the increased proximity of adenine nucleotides before they conducted the study.

Quality scientific research is characterized by findings which: 1) are clinically significant, and/or 2) advance our basic knowledge. Although this study may trivially advance our basic knowledge, the clinical utility of this study is minimal. It would be a serious scientific mistake to presume that an increase in adenine oxidation will have any long-term adverse implications for cells, organisms or people. Until we know what oxidative damage is or is not being repaired, we cannot even begin to predict whether this specific effect of vitamin C on DNA would be expected to be positive or negative. DNA repair enzymes, like antioxidant enzymes, are readily inducible (i.e., producible on demand). I wouldn’t be surprised to discover that DNA repair enzymes are downstream of iron sites and thereby upregulated along with antioxidants. There are plenty of studies which show vitamin C to have a significant genome-stabilizing effect overall [see Fraga et al.]. I am certainly not reducing my intake of vitamin C based on this study. ——SWF

Ames B N and Gold L S. Endogenous mutagens and the causes of aging and cancer. Mutation Research 250(1-2): 3-16, Sep-Oct 1991. “A very large oxidative damage rate to DNA occurs as part of normal metabolism. In each rat cell the steady-state level is estimated to be about 10exp6 oxidative adducts and about 10exp5 new adducts are formed daily.”

Fraga C G et al. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA 88(24): 11003-6, 15 Dec 1991. “The very high endogenous rate of oxidative DNA damage and the importance of dietary ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA. ...When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%. These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers.”

Podmore I D et al. Vitamin C exhibits pro-oxidant properties. Nature 392: 559, 9 April 1998. 30 healthy subjects were given 500 mg daily of vitamin C for six weeks.

Question: Yesterday, there was a story about a recommendation by the National Academy of Sciences that “large segments” of the American public should take vitamin supplements. Today, there’s a story that 500 mg vitamin C can cause genetic damage. Is this science or politics? ——PJ

Answer: In this US version of the story, the helpful voice of Victor Herbert, M.D., was added to those of the British researchers who did the study. For those unfamiliar with Dr. Herbert, he is a notorious “quackbuster” fostering vehement anti-vitamin rhetoric in the United States about any danger — real or perceived — from dietary supplements. The eminent Dr. Herbert’s involvement hints that there may be an overt political agenda behind the publicity. In other words, why would a relatively obscure indeterminant finding generate such massive world-wide publicity? The answer may be found in the article in the London Times which stated, “The government has moved to limit the use of vitamin B-6 because of safety concerns. Jeff Rooker, the Food Minister, had already announced that vitamin C was his next target.” Aha! The Food Minister needs a perception of danger to justify his policies. If danger is not an issue in real life, extrapolate from a superficial and inadequate scientific finding to create some perceived danger. As long as the public is scared, they will let politicians and bureaucrats do anything.

The political alignment between Jeff Rooker, the vitamin-prohibiting British Food Minister, and Victor Herbert, the quintessential US quackbuster and anti-vitamin ideologue, provides a clear rationale about how this minor study was transformed into worldwide news.

Years ago, Victor Herbert hit the news with warnings about the dangers of vitamin C towards vitamin B-12 absorption. Extrapolating from test-tube experiments, Herbert postulated that high-dose vitamin C supplements would interfere with B-12 assimilation and function. He was wrong. People taking high-dose vitamin C, even for multiple years, did not show any signs of B-12 deficiency. Such is Herbert’s track record crying “Wolf, wolf!”

Test-tube experiments and unassociated metabolic measurements are a far cry from real life. Extrapolate such results at your own peril. ——SWF