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Last week, I posted an article on N-acetylcysteine (NAC) that mentioned a number of health conditions for which it is believed to be helpful. I also discussed my experience with the supplement and how and why I’ve used it. As is usual with articles, some of the feedback I got was along the lines of “so does it work?” That’s a good question.

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Does A Supplement Work For You? It’s An Educated Guess!

This feedback got me to thinking about the same question about the many nutritional supplements I take. Some of them I know work because I know that I can sleep better when stressed out far more often than used to be the case, my cholesterol and triglyceride levels have dropped, and my liver function tests have improved. Some of them, I truly don’t have a clue as I can’t find any obvious effects for myself.

In my experience, supplements can usually be grouped into about four categories:

1. Supplements that have such an obvious effect that you can be sure they did something helpful or harmful.

   Some supplements have very drastic effects that make it obvious they work. For instance, a friend told me about his experience with glycine, a simple amino acid, and how it helps him sleep. I’ve found that taking about 3 to 4 grams of glycine on an empty stomach on nights when it is hard to sleep usually puts me to sleep very quickly about 80% of the time, even if I was restlessly rolling around in bed for an hour having worried thoughts.

2. Other supplements have a less obvious effect, but still seem to be doing something noticeable.

   For instance, theanine, GABA, and ashwagandha do not have such a drastic effect on sleep for me as glycine does. But I believe they have helped with managing stress and improving sleep during stressful circumstances, too. Taken without much else in the way of food or supplements, glycine might put me to sleep when I don’t want to sleep. Theanine, GABA, and ashwagandha don’t do that.

3. Supplements which seem to be doing something together, but you’re not sure which ones are responsible.

   I’ve tried fish oil, niacin, artichoke extract, red yeast rice, and many other supplements to reduce LDL cholesterol and triglycerides. Something definitely worked, but I’m not sure of the precise cause. Some of these supplements take months to start showing effects, others may have zero effect for certain people and significant effect for others. I have taken many supplements that are supposed to help in this area after trying unsuccessfully for years to improve these areas via improved diet and exercise. Somewhere along the way of varying supplements and dosages, I started getting positive results. But I’m not really sure what it was. Along the way, my liver function tests, improved, too. I’m reasonably sure it has to do with supplement changes, but as I changed several at once I’m not really sure which ones are responsible other than strongly suspecting the large doses of fish oil (usually about 4200 mg of Omega-3 fish oils per day, meaning about 7 “high concentration” Life Extension Mega EPA/DHA softgels!) and the increase from 1000 mg of niacin to 2000 mg of niacin per day are what did the trick for the triglycerides. I think it is possible the red yeast rice wasn’t doing much for me and that reducing its dosage to one 600mg capsule per day (I used to take four 600mg capsules per day) may have helped on the liver function tests. But I’d guess my use of NAC and silymarin is more likely to have helped on the liver function tests. Still, that’s just a guess.

4. Finally, there is a whole long list of daily supplements that don’t seem to have any obvious effect.

   Multivitamins, calcium, vitamin C, vitamin D, vitamin E, etc. are among these. How do you detect whether a vitamin is having a helpful effect if there’s no test for it or the tests are direct measurements of the vitamin level?

For most of the supplements I take, I can’t say with any certainty whether they work or not for me. For instance, how can you know whether taking vitamins is really helping? Most of them do not have effects that show up clearly in the usual blood tests you have done by a doctor or lab except for measurements of the vitamin itself.

The bottom line for most supplements is that it’s an educated guess as to whether they work for a particular person. You can improve the guess by getting more testing data and carefully monitoring your diet and supplements and health conditions, but even then it is still going to be an educated guess.

Vitamin D Example: You Can Measure It Easily, But What Does It Do?

While I have been keeping my vitamin D levels up via what others may consider fairly extreme D3 supplements and have the test results to demonstrate more moderate supplementation wasn’t enough for me, I don’t have any conclusive personal evidence that higher vitamin D levels has helped me. I never had osteoporosis, multiple sclerosis, diabetes, colon cancer, or any of the other host of illnesses that vitamin D helps prevent and/or resolve. So even with test data that shows my vitamin D blood levels, how am I to know it is “really working” or not?

Dr. John Cannell of vitamin D fame has stories about his work at Atascadero State Prison during which he observed his patients who were supplemented with vitamin D go through a flu season and nobody got sick, but the other wards of patients with no vitamin D supplements weren’t so lucky:

(from Epidemic Influenza And Vitamin D)

I guess our hospital was under luckier stars as only about 12% of our patients were infected and no one died. However, as the epidemic progressed, I noticed something unusual. First, the ward below mine was infected, and then the ward on my right, left, and across the hall – but no patients on my ward became ill. My patients had intermingled with patients from infected wards before the quarantines. The nurses on my unit cross-covered on infected wards. Surely, my patients were exposed to the influenza A virus. How did my patients escape infection from what some think is the most infectious of all the respiratory viruses?

My patients were no younger, no healthier, and in no obvious way different from patients on other wards. Like other wards, my patients are mostly African Americans who came from the same prisons and jails as patients on the infected wards. They were prescribed a similar assortment of powerful psychotropic medications we use throughout the hospital to reduce the symptoms of psychosis, depression, and violent mood swings and to try to prevent patients from killing themselves or attacking other patients and the nursing staff. If my patients were similar to the patients on all the adjoining wards, why didn’t even one of my patients catch the flu?

A short while later, a group of scientists from UCLA published a remarkable paper in the prestigious journal, Nature. The UCLA group confirmed two other recent studies, showing that a naturally occurring steroid hormone – a hormone most of us take for granted – was, in effect, a potent antibiotic. Instead of directly killing bacteria and viruses, the steroid hormone under question increases the body’s production of a remarkable class of proteins, called antimicrobial peptides. The 200 known antimicrobial peptides directly and rapidly destroy the cell walls of bacteria, fungi, and viruses, including the influenza virus, and play a key role in keeping the lungs free of infection. The steroid hormone that showed these remarkable antibiotic properties was plain old vitamin D.

All of the patients on my ward had been taking 2,000 units of vitamin D every day for several months or longer. Could that be the reason none of my patients caught the flu? I then contacted Professors Reinhold Vieth and Ed Giovannucci and told them of my observations. They immediately advised me to collect data from all the patients in the hospital on 2,000 units of vitamin D, not just the ones on my ward, to see if the results were statistically significant. It turns out that the observations on my ward alone were of borderline statistical significance and could have been due to chance alone. Administrators at our hospital agreed, and are still attempting to collect data from all the patients in the hospital on 2,000 or more units of vitamin D at the time of the epidemic.

Cannell and his hospital have a staff and money for blood draws, tests, and supplements, and they still aren’t sure what is going on themselves. In the meantime, pending more research, he and his colleagues are pretty sure he’s on to something and many of them are taking much larger doses of vitamin D, even up to 200,000 IU or so per day for three days at the outset of colds and flus.

(from Epidemic Influenza And Vitamin D)

I subsequently did what physicians have done for centuries. I experimented, first on myself and then on my family, trying different doses of vitamin D to see if it has any effects on viral respiratory infections. After that, as the word spread, several of my medical colleagues experimented on themselves by taking three-day courses of pharmacological doses (2,000 units per kilogram per day) of vitamin D at the first sign of the flu. I also asked numerous colleagues and friends who were taking physiological doses of vitamin D (5,000 units per day in the winter and less, or none, in the summer) if they ever got colds or the flu, and, if so, how severe the infections were. I became convinced that physiological doses of vitamin D reduce the incidence of viral respiratory infections and that pharmacological doses significantly ameliorate the symptoms of some viral respiratory infections if taken early in the course of the illness. However, such observations are so personal, so likely to be biased, that they are worthless science.

In other words, he’s a doctor who is researching this and has a lot of data on it, but he still isn’t sure about whether it works or not. So he’ll take his best educated guess until better data is available.

While I believe that vitamin D probably is effective at boosting immune system function and have been taking more than 3000 IU of vitamin D daily for more than a year, recently I got a cold or flu that lasted an unusually long time, almost three weeks. It was the first in perhaps over a year.

Does this mean the vitamin D didn’t work? Or does it mean I wasn’t taking enough? There’s no way to know from my one personal experience. When I was first tested for vitamin D months ago after seeing the increasing evidence of widespread deficiency, I was very surprised to find that my vitamin D blood levels were only a little over 40 ng/mL. This is a far cry from th 50 to 80 ng/mL for optimal levels, even though I had been taking 5000 to 6000 IU of vitamin D3 per day for several months prior to the test and about 2000 to 3000 IU daily for a few months before that. By my estimates, I’d need around 8000 to 9000 IU per day to get around 65 ng/mL which is around the middle of the optimal range. That’s a lot of vitamin D by most people’s opinions, but still well within safe limits based upon many studies. I have had my CBC (Complete Blood Chemistry) tested periodically and nothing appears to have changed with my calcium levels, but haven’t retested my vitamin D just yet. I’ll wait until early 2009 after the period of least sunshine of the year versus my previous test which was not long after the annual peak sunshine levels in June.

I’ve also decided that on balance, I’d rather end up shooting for the high end of the optimal range as it doesn’t appear there is much danger of adverse health effects until vitamin D blood concentrations go well beyond 100 ng/mL and it’s not like I’m letting this go completely unmonitored. So between the various supplements containing vitamin D that I’m taking each day (two 5000 IU softgels from Puritan’s Pride, a Costco multivitamin with 400 IU, and a Life Extension Vitamin D/Iodine capsule with 1000 IU), I now get about 11,400 IU per day and as usual don’t spend much time in the sun. In theory, that should put me right about at 80 ng/mL or perhaps a bit lower because of the reduced sun exposure during winter. We’ll see.

We’ll also see if I drop dead from the H1N1 flu season this year. But even if I don’t, I still can’t truly claim that vitamin D “worked”, can I? Still, I’m going to keep taking it because it appears to me the “educated guess” is that it is a beneficial and inexpensive supplement.

NAC May Have Helped My Liver Function, But I’m Not Sure

For NAC in particular as I mentioned in the article linked above, I’ve been taking it for almost two years. I don’t have any acute or chronic medical condition which could improve or worsen that would obviously and easily be tied to NAC. Anecdotally, it does appear that since I started taking NAC and silymarin (milk thistle) that my liver function tests such as AST and ALT have improved markedly. While it makes sense that NAC and silymarin could do this, it could be due to other factors entirely. Maybe I had some undetected liver infection that cleared up. Maybe improving cholesterol levels that I attribute to other supplements such as fish oil and niacin (vitamin B3 in nicotinic acid form) got rid of some of the fat in my liver and now it is working better. Maybe my reduction in red yeast rice capsules helped improve liver function tests, although I somewhat doubt that’s it because it didn’t seem to raise them when I first started taking it. Maybe it is a combination of all of these. I really don’t know, but wish I did because I could save a lot of money on supplements if I knew exactly which ones work and which ones don’t.

Nutritional Supplements Often Have Subtle and/or Long-Term Effects

This realization that it is so hard to know what supplements work is a bit disturbing considering how expensive they can be. But I look at it as a bit of a high-stakes gambling experience in which my “educated guesses” improve the odds. Even though I’m not a gambler by nature, every day I’m gambling with my life that the things I do will keep me living longer and enable me to have a more or less happy life, help other people starting with my family and friends, and not go broke in the process. Nutritional supplements are my way of stacking the deck that makes my desired outcome more likely even though I can’t be sure of exactly which ones are helping the most and which ones the least.

My perspective on nutritional supplements is that most have subtle effects that take weeks, months, and even years to be evident for a single person. Even then, these effects are often apparent only via the results of blood tests if you happen to have before and after test data.

While it may be that I waste $2000 per year on supplements that don’t do much compared to the $1000 per year that do a lot, I can’t be sure which ones work and which ones don’t. And even if I knew that for the moment, it could be that this changes entirely due to illness, diet changes, stress levels, or some chance situation. So the bottom line is that I really don’t know for sure one way or another about more than half of the supplements I’m personally using.

Medical Studies Help Provide Insight

Whether you’re a doctor like John Cannell or a “vitamin nut” who studies all she can about healthcare and nutritional supplements, there’s really no way to know from small groups of people whether anything works unless it perhaps falls into that first category of supplements that have very immediate and obvious effects. Even then, as I mentioned, there can be factors the blunt those effects. If I take 4 grams of glycine after a big meal with a couple of classes of diet cola (not that I get a caffeine rush, but it might do something), the glycine doesn’t do much of anything. If I take it four hours after dinner, I might have trouble getting to bed before I fall asleep.

This inability to figure out what works from personal anecdotes and small experiments is why well-designed medical research studies are so valuable. They can do double-blind studies with placebo control groups and dozens, hundreds, or even thousands of people in the studies and follow them for months or years. They provide and document blood tests and other medical tests before, during, and after the experimental treatment to detect what happens. The sheer number of people and the control groups help erase the “noise” of illnesses, medications, stress, etc. that would often drown out the “signal” of health improvements many of the individuals in the study.

For instance, if one of the study participants gets hit by a car and hospitalized then catches pneumonia in the hospital and takes two months to recover in the middle of a six month study, that person’s abnormal results can be discounted without ruining the study or might have so little influence if there are hundreds of study participants that they don’t matter. But if you are trying to evaluate the results on yourself, even something minor like a cold or a sprained ankle could seriously interfere with your ability to determine results. And do you really have the money to pay for repeated blood tests before, during, and after “test periods” of a supplement? Many of these tests cost far more than a year or more usage of the supplements do.

Medical Social Networking Sites

Quality clinical studies are expensive and can take years to get results. Then there’s the problem of who will fund them. It’s often very, very difficult to get anybody to pay for a study for a supplement or a drug that is off-patent. It could literally be the case that there are inexpensive supplements and drugs that could save millions of lives per year, but since no big pharma company can make much money on them, the “business decision” is to not fund studies on such substances as there is no “big money” to be made on them.

There’s a great deal of long-term promise for helping speed up the determination of supplements and off-patent drugs that work and why in web sites such as PatientsLikeMe. These sites help to collect data from many people and turn them into graphical presentations that can show common side effects, efficacy estimates, dosages, and other helpful information. But it’s going to take a lot more people using them and some way to keep the data relatively “clean” so that noise and bias doesn’t dilute the results.

For instance, take a look at their web page on vitamin D reporting for patients suffering from multiple sclerosis. There are a lot of people reporting data. But many of them can’t tell if it is working or not. Some of them can’t even agree on what to call it. If you looks through the “treatments” they list, you’ll see that vitamin D and vitamin D3 and cholecalciferol are all listed.

I’m going to keep my eye on these kinds of sites, but suspect it may be several more years before they truly start to become widely useful for many people. At the moment, PatientsLikeMe has about 45,000 people participating by entering their medical information. You may find that even if this site doesn’t have information useful for your situation yet, the site could still be helpful for you to track your own health. Take a look at this example “patient view” that shows a person who is reporting taking various supplements along with weight, stress, and mood changes. If you could keep up with entering the data, you might discover some interesting correlations between aspects of your life, diet, supplements, and health.

“Experiment” To Evaluate Supplements for High Homocysteine

If you’re truly interested in seeing how individual nutritional supplements work on you and have the time, money, and obsessive determination to investigate, probably your best best is to find problem areas in your health that can be verified by obvious symptoms and/or blood tests and then to repeatedly attempt to tune your supplements to resolve the problems while periodically retesting to see the progress.

For instance, say you find that you have high homocysteine levels, a common risk factor for cardiovascular disease that is relatively inexpensive to test, and want to do something about i. You might make a list of supplements that could help. Those might include folic acid, L-MTHF (L-methyltetrahydrofolate, the active form of folic acid), vitamin B12 variants including cyanocobalamin and methylcobalamin, choline, lecithin, TMG (trimethylglycine), and NAC. All of them have been found to help lower homocysteine levels in medical studies, but not every one works for every person. So to be really objective, you would have to try each of these and have before, during, and after tests plus have a “wash-out” period between supplements. In three or four years, you might have found out that for you here is how various supplements affect your homocysteine level:

• Folic acid and cyanocobalamin don’t help much, cutting your homocysteine level by about 5%. It’s because you don’t absorb and metabolize them well, common problems, yet most people don’t know they have such problems until some clearly evident health problems like worsening neuropathic pain cause a doctor to order tests to check for folate and B12 deficiencies.
• Lecithin helps a little, dropping homocysteine by 8%.
• Choline, TMG (trimethylglycine), and NAC help more, each dropping homocysteine by about 30% to 50%.
• L-MTHF (L-methyltetrahydrofolate) and methylcobalamin (the active form of vitamin B12) help the most, dropping homocysteine by 60%.

To get this data, you may have spent $3000 on tests and $500 on supplements. In the meantime, your cardiovascular health declined some because your homocysteine and other blood parameters were vacillating up and down as you jerked around your supplement package. But now you know the answer. Was it worth it? Maybe you’ll now save $500 per year on supplements but will have a heart attack three years from now that you wouldn’t have had if you had just used all of them.

My Strategy: Moderate Doses of Many Supplements Looking for Good Values

As for me, I’d just take all of them, looking for good prices on every one and taking medium to moderately high dosages of each. Every one of those supplements I listed for improving homocysteine levels also has other beneficial effects. Choline and lecithin help boost the bodies’ ability to produce acetylcholine, a critical neurotransmitter. TMG and choline provide methyl donors for converting homocysteine into SAMe (S-adenosylmethioninine). SAMe is a supplement that is very expensive at typically recommended dosages but which studies show can help with mood, depression, joint pains, and even liver function. A month of plentiful TMG and choline supplements might cost less than half of what a month of moderate SAMe supplements would and do your body a lot more good, too. While I don’t truly know whether or not my body metabolizes folic acid and cyanocobalamin well, these nutrients are very common ingredients in multivitamins and B complex vitamins. It’s unlikely you could get too much of them unless you went really bonkers with them, but it is possible to get too little or enough folic acid that it hides a vitamin B12 deficiency. So it is better to take some of each.

As for “good values”, here’s an example of what I mean beyond the comments about SAMe. I take the bioactive L-methyltetrahydrofolate and methylcobalamin forms of folic acid and vitamin B12 as part of a B-complex capsule I found that was much less expensive than the prescription Metanx tablets my doctor used to prescribe. If you have good health insurance, however, you might ask your doctor about taking one or two tablets per day of Metanx, especially if you have any conditions such as depression, anemia, low energy levels, sleep problems, neurological problems, or neuropathic pain. Without insurance, it could cost $60 (or even $120 per month for what amounts to two vitamin tablets!) for just that one supplement, whereas my non-prescription approximation of it costs closer to $20 per month.

One of the keys for me to select supplements is reviewing the latest medical research news to watch as new studies show up and see if there are trends. If I see several studies showing that a supplement is promising, I’ll take note, see how expensive the supplement is, and then investigate it further if it doesn’t look too obnoxiously priced.

Obviously Internet tools are very helpful to all of this. I’m also really impressed with the work of Life Extension on educating the public and funding studies. Even if you don’t plan to buy anything from them, I’d urge you to click on over to the brief write-up from a few months back about how to get a free year subscription to their monthly magazine. It’s definitely worth an hour or two of reading time per month if you are at all interested in health and nutrition.

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Further Reading

Review: 1FAST400 N-Acetylcysteine (NAC) Bulk Powder

Adjusting Your Vitamin D Intake to Optimal Levels

Cost-Effective Medications and Supplements

Meaning and Interpretation of Medical Tests

Free One-Year Subscription to Life Extension Magazine

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These statements have not been evaluated by the Food and Drug Administration. The products mentioned in this post are not intended to diagnose, treat, cure or prevent any disease.

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