When Supplements Really Work, Part I: Supplements Perform Like Drugs
HHN: You write in The Supplement Handbook: "To me, there is no difference between an effective supplement and a drug for a specific medical condition… When a supplement works like an available drug, you should have more confidence in its ability to have a tangible effect." Have supplements have been scientifically proven to perform as well as or better than conventional treatments for given conditions?
MM: There are so many examples, I could write pages upon pages and put you to sleep without using melatonin. Let’s review three that are changing or have already changed medicine for countless patients:1Alzheimer’s Disease: How many effective treatments do we have for AD patients? A recent Cleveland Clinic report states that 99.6% (244 out of 245) of Alzheimer’s clinical trials have failed over the past decade.
Compare that with one of the longest and best clinical trials ever conducted in the U. S, published in the Journal of the American Medical Association:"People with mild to moderate Alzheimer’s taking 2000 IUs of vitamin E daily in addition to standard meds had a 6+ month reduction in functional decline."Individuals with mild to moderate Alzheimer’s disease taking 2000 IUs of vitamin E per day in addition to standard medications/ acetylcholinesterase inhibitor (AChEI) drugs experienced an over six-month reduction in functional decline and reduced caregiver time by two hours daily. This is the second such major trial to show a benefit at the same dosage, the first having been published almost 20 years ago in the New England Journal of Medicine.
Vitamin E supplements have not been shown to prevent Alzheimer’s or help with mild cognitive impairment, but for people with mild to moderate Alzheimer’s, I recommend discussing supplementation as an additional therapy with your doctor ASAP.2 Macular Degeneration: A dietary supplement is now recommended as one of the primary treatments for many patients with intermediate to advanced stages of age-related macular degeneration, as it has been shown to prevent vision loss! Based on the 2013 Age-Related Eye Disease Study 2, the National Eye Institute recommends this exact formula:
- 500 mg of vitamin C (ascorbic acid)
- 400 IU of vitamin E (dl-alpha-tocopheryl acetate)
- 25−80 mg of zinc (zinc oxide)
- 2 mg (cupric oxide)
- 10 mg Lutein
- 2 mg zeaxanthin
Note: The formula has not shown an ability to prevent this disease, but specifically helps those in the intermediate to advanced stages.3 Migraines. Few individuals realize that American Academy of Neurology guidelines recommend butterbur extract as having class A evidence—one of its highest recommendations for preventing migraines."Taking 75-milligrams of butterbur extract twice a day reduced the frequency of migraine attacks by about half."Taking 75-milligrams twice a day reduced the frequency of migraine attacks by about half. Maximum response was achieved after three months with a product containing at least 15% petasins, so always look for this on the label. The Petadolex brand has the most research behind it.
In addition, there’s excellent preliminary data, published in a 2012 report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society, that taking up to 400 milligrams of vitamin B2 (riboflavin) daily can also reduce migraine frequency.
Isn’t this ironic? According to the FDA (U.S. Food and Drug Administration), a dietary supplement "is not intended to diagnose, treat, cure or prevent any disease." However, this is precisely why a neurologist or ophthalmologist would recommend these migraine and macular degeneration treatments.
Supplements & Drugs: Is There a Difference?
HHN: That brings to mind your comment in The Supplement Handbook: "The difference between a drug and an effective supplement is only perception, not reality… Aspirin is created from willow bark and the diabetes drug metformin comes from French lilac." If that’s the case, what underlies the U.S. government’s decision to label a product a "supplement" or a "drug"?
MM: Let’s compare the two according to the FDA. I’m parphrasing the drug definition:
- Dietary supplement: A product intended for ingestion that contains a dietary ingredient [a vitamin, a mineral, an herb or other botanical, an amino acid… a concentrate, metabolite, constituent, or extract] intended to add further nutritional value to supplement the diet… Some supplements can be used to help you reduce your risk of disease.
- Drug: An FDA-approved compound or compounds based on extensive basic and clinical research that ultimately is tested in a rigorous and final Phase 3 trial to prove it can treat, cure, or prevent a disease or medical condition either similar to or better than the standard of care.
Can you tell me the difference? In my opinion it’s nebulous—which is why, for example, in the U.S. you can buy fish oil or omega-3 as a dietary supplement and as a prescription drug (Epanova, Lovaza, Vascepa…).
Usually the distinction comes down to requirements: Strict clinical trials are required for FDA approval of drugs, but no trials are needed to bring supplements on the market.
HHN: Why does the FDA require strict clinical trials for drugs but none for supplements?
MM: It’s politics. The general consensus seems to be that mandating supplement testing or regulation as is done for drugs would be politically unpopular, since most Americans—and, in my experience, most politicians—take supplements.
A strong anti-big pharma movement also plays into this. Many Americans feel understandably outraged by the ridiculous expense of certain drugs. Viagra, for example, is now $40/pill for men suffering from a medical condition, such as erectile dysfunction after prostate surgery. There’s no justification for this pricing, because research and development was not that expensive to justify the current pricing schedule for this once-shelved drug.
This public perception that big pharma is "bad" and mom and pop supplement company is "good," that "mom and pop" are just trying to sell natural products to help people and big pharma is getting in the way, supports keeping the rules as they are.
That said, today supplements are an arguably $30+ billion industry, that industry has in some ways taken on a big pharma feel and profit, and money doesn’t talk but shouts!"Massive money and political movements, including supplement industry lobbying groups supporting some politicians, are behind keeping the supplement rules status quo."So, in reality massive money and political movements are also behind keeping things status quo. Among them are supplement industry lobbying groups supporting some politicians, such as Senators Orrin Hatch of Utah and Tom Harkin of Iowa, both of whom staunchly back legislation to keep dietary supplements as a standalone, unregulated FDA category.
This is doubly problematic. First, there’s considerable lack of government oversight of an industry that counts more than one half of the American public as its consumers, which has led to some perilous outcomes. Second, in those instances where excellent scientific research supports using dietary supplements to prevent or treat disease, such as the Alzheimer’s, migraine prevention, and macular degeneration examples above, the FDA does not allow the company who made the supplement to overtly advertise and promote the study results, because that would be saying the supplement acts like a drug. Both of these regulations make no sense!
Good Practices, Poor Oversight
HHN: Are U.S. government safety regulations completely lacking for dietary supplements? What kinds of perilous outcomes have ensued as a result?
MM: Over the last decade, with public pressure mounting on the quality control issue, the FDA devised a "current good manufacturing practices" or cGMP rule that supplement companies are supposed to follow. It is an excellent first step by the FDA that breaks new ground in encouraging and establishing an ongoing standard or threshold of safety and quality in the manufacturing process.
The problem or catch really is, if I told you the highway speed limit was 55 MPH but you knew few cops patrolled the highway to enforce it, what speed would you drive? In other words, the FDA doesn’t have the person power to enforce cGMP, so while companies say they are following cGMP, there’s no way for consumers to be certain until the products are inspected by the FDA or an independent third party in the field. My sense, from the FDA auditing that does occur, is that the vast majority of companies probably do follow cGMP, but the small minority of companies not abiding by the rules can endanger consumers. Every year the FDA does find issues with some companies. They’ve either had to simply and quickly resolve the issue or, if there’s something particularly egregious, which has happened, the company may no longer be able to function.
Not having enough FDA inspectors has led to hazardous consequences. Last year, for example, 20% of serious liver toxic events in the U.S. were due to supplements, most of them fly-by-night weight loss, energy-booster, colon-cleanser, and body-building types of products"Last year, 20% of serious liver toxic events in the U.S. were due to supplements."that mixed a bunch of ingredients that had never being tested together in a bottle. More than 125 serious liver toxic events—liver failure, need for a transplant, and even death—have been documented at 8 large hospital referral centers that participated in tracking such incidents, which indicates that this number is just a fraction of a much more widespread problem throughout the U.S. Once a product is linked to this kind of problem, the FDA will attempt to have it removed, but this can take time to prove cause and effect.
In short, if a product has only been on the market a few months and has been issued by a company you’ve never heard of or one without proven quality control (see Part II to help determine which companies have higher levels of quality control), don’t be one of the first to try it.
The European & Canadian Model
HHN: Do other nations regulate dietary supplements differently?
MM: Yes, Canada and many European countries, such as the U.K., France, Germany, and Italy, generally require some clinical proof of safety, efficacy, and quality, with submitted documentation, before manufacturers can make a claim, distribute and sell a product. For example, Health Canada, the FDA equivalent for supplements in Canada, required extensive testing of alpha lipoic acid for diabetic neuropathy and even different forms of vitamin C before they could be sold over the counter in health food stores throughout the country.
The real difference between these countries and the U.S., I think, is the level of normal day-to-day governmental involvement with humans. Canadians and citizens of most European countries are used to their government-run health care and indeed their government’s involvement in most public health matters. In this environment, regulating dietary supplements using a system that’s somewhat similar to drug regulation is not a political hot potato as it is here in the U.S., where there’s always tension between individual rights and societal responsibility, and dietary supplements dance on this fine line every day.
Proposed Protection Plan
HHN: What do you believe is the optimal solution to protect supplement consumers in America?
MM: I don’t believe supplements should become prescriptions. But at the same time, I think the government should compel supplement companies to be audited by one of the credible third-party quality control groups that do exist. (See Part II.) It makes no sense that tomorrow I could simply set up the "Dr. Moyad Supplement Company" and no one could require me to prove that what I am selling is at least safe, let alone contains the active ingredients touted on the bottle.
Selecting the Supplements You Need
HHN: These days, supplements are also being promoted to potential consumers left and right. What is the best evidence-based method for determining which supplements someone really needs?
MM: Here are 5 tips:1Get really comfortable with your family disease tree. What diseases did your family members have and why? What did they die from and why? This can help you figure out what you may be at high risk for. So if there is a family history of migraines and you’re starting to suffer from migraines, you might want to take something to prevent future migraines.2Get heart and mentally healthy first. With good diet and exercise habits, try on your own to achieve optimal heart health as measured by healthy cholesterol, blood pressure, blood sugar, and weight—"In the society that’s number 1 in global population longevity, Andorra, it’s unusual for residents to take supplements unless they’ve been diagnosed with or at high risk of a medical condition."the big preventive numbers that really make or break whether or not you’re predicted to live a longer, healthier life. Only then decide if you need some pill support for those major issues, and if you do, get the support you need. That’s the protocol in the society that’s number 1 in global population longevity: Andorra, in southwestern Europe. It’s unusual for residents to take any pills or supplements unless they’ve been diagnosed with or are at high risk of a medical condition.
So, for example, if you have high cholesterol that cannot be controlled by diet and exercise, red yeast rice supplements become an option. If diet and exercise cannot help male sexual dysfunction, taking L-citrulline supplements for one month may help.3Do targeted dieting first. If a physician tells you you’re low in a particular nutrient, see if you can elevate it with nutrition before taking a supplement for it. There may be food sources you haven’t thought of. Let’s say you’re low in calcium. The Recommended Dietary Allowance is 1000−1200 milligrams daily. Both almond and cashew milk are great sources of calcium. Blue Diamond, the leading brand of almond milk, has 455mg calcium in just 8 ounces, so you can get practically all the calcium you need just by drinking 2 cups daily.4Choose supplements proven to help treat conditions, diseases, or their side effects, instead of taking supplements for general prevention, except for a multivitamin, which has been proven to help a little. The beauty of most supplements is not for preventing disease but in treating them. Unfortunately public perception is just the opposite: that supplements are for promoting health and not for combatting disease like a drug. Allowed advertising plays into this, as does the lack of objective education for health care professionals and the public.5If you’re taking prescription medications, ask yourself and your doctor if a supplement might be needed to rectify any nutritional deficiencies that are "quiet" side effects of the drugs."Many of the real nutritional deficiencies I see today occur from prescription medication use."Many of the real nutritional deficiencies I see today occur from prescription medication use. For example, acid reflux drugs lower magnesium and vitamin B12 levels, and so does metformin, the largest selling type-2 diabetes medication. And high dosages of zinc supplements (80 mg or higher) can create anemia due to a copper deficiency.
HHN: Why do you recommend not consuming dietary supplements for general prevention, except for a multivitamin? Isn’t it true that just because scientific study hasn’t yet proven that other dietary supplements help prevent disease, some supplements may well do so?
MM: This could be true, false, or make no difference. The hard-core clinical evidence is not there to make that decision right now for many supplements, and the brilliant Hippocratic oath, "first do no harm," is just as relevant today. In fact, now, more than at any other time in our medical history, we know that taking a supplement for prevention without evidence can have dire consequences in the wrong group. For example, the largest dietary supplement trial in the U.S., known as SELECT, found a higher chance of prostate cancer and perhaps aggressive prostate cancer in healthy men taking high-dose vitamin E (400 IU per day) and/or selenium (200 micrograms per day), especially when they had replete levels of some of these nutrients in their blood.
HHN: You said that people should have confidence in a supplement’s ability to have a tangible effect. Is it a myth that so-called "natural" dietary supplements take longer to work than drugs because they’re operating more subtly on the body’s systems? How should consumers determine appropriate responsiveness from their supplements?
MM: Apart from a multivitamin, in my opinion this idea that supplements subtly change your life is primarily a marketing ploy.
I apply 3 rules to determine if patients or individuals need to continue taking a pill or supplement:1 Subjective Test (aka Guinea Pig Approach)
Stop the product for at least one month and see if you feel any better or worse or the same. The cessation period depends on the person, condition, and situation: it could be two weeks in the case of cholesterol, 1 month in the case of mood, and 6 months to a year in the case of bone health. This approach works very well for supplements, just as it does when people stop eating certain foods to discover if they have intolerances to those foods. Patients who go off their supplements often tell me they feel no different or actually feel better, and then they simply stop the pill, saving time and money. Other times, people say they feel worse or more fatigued or got ill more often after stopping their supplement. That is a good indication they may need the pill.2 Objective Test (aka Laboratory or Numbers Approach)
Is the supplement you’re taking changing any single laboratory-based parameter that suggests you are becoming more healthy? I like to look first at cardiovascular disease (CVD) parameters because CVD has been the number 1 cause of death in women and men over age 30 for 114 of the last 115 years. In fact, I don’t like to recommend any pill unless I know its impact on heart health. Again, "First do no harm," right?
So, what CVD numbers are changing for the bad or good with your pill? Is it dropping your cholesterol, blood pressure, blood sugar, or weight? If the answer is nothing or things actually get worse, of course I become a little skeptical.
Working with a good doctor is critical in getting the objective test answered well. A doctor, pharmacist, or other health care practitioner who applies broad strokes to supplements—e.g., all bad or all good—makes me nervous. Find one with an open and inquisitive mind.3 Practice Alternative Lifestyle Change First
Ask yourself: Is there a lifestyle change that can preclude my having to take this supplement or drug, get me off it, or at least reduce its dosage?
A great example of lifestyle trumping drugs is the landmark Diabetes Prevention Program clinical trial published in 2002 in the New England Journal of Medicine. This study showed that the drug metformin reduced the risk of type II diabetes in high-risk patients by 31% compared to placebo, propelling metformin into hundreds of other clinical trials. Now it is the number 1 type II diabetes drug and one of the popular pills worldwide.
But an amazing thing happened in this clinical trial that few people realize: A lifestyle intervention—150 minutes of exercise per week and 7% weight loss—actually worked much better than metformin!"For type 2 diabetes prevention, 150 minutes of exercise per week and 7% weight loss worked much better than the number 1 diabetes drug."It reduced type 2 diabetes risk by 58% compared to placebo, a major improvement over metformin’s reduced risk of 31%, and the lifestyle changes had significantly fewer side effects than the drug. Women and minorities were well represented in this trial—not often the case in major clinical studies—so we know that lifestyle works in diabetes prevention for almost everyone.
Here’s another excellent example of the effectiveness of a lifestyle intervention. In 2013, researchers conducted one of the most extensive analyses of exercise versus medication: a review of 305 randomized trials with 339,274 participants. They concluded: "Exercise and many drug interventions were often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes." Wow!
This is why I recommend applying moderate lifestyle changes first and foremost to determine whether a supplement or a drug is necessary. Taking better care of yourself is the ultimate truth- detector test of what your body ultimately needs.
HHN: It’s noteworthy that you, the author of The Supplement Handbook, are cautious about supplement use.
MM: A supplement, just like a drug, can absolutely make your life better if you need it—and worse if you don’t. We talked about the extreme case of supplements leading to liver toxicity. A more common problem is over-supplementation."Daily doses of 1000+ mg Vitamin C over just a few weeks increase the risk of kidney stones."Research shows that mega-doses of certain athletic supplements may hinder the benefits of exercise by not allowing oxidative stress to signal to the body that it needs more mitochondria or cellular changes to build long-term endurance. We also know that too much magnesium, sometimes resulting from a combination of supplement and diet, can result in diarrhea. Daily doses of 1000+ mg Vitamin C over just a few weeks can dramatically raise oxalate levels in the urine and increase the risk of kidney stones. There are many other examples.
And if this isn’t reason enough to get healthy first, consider this: Researchers have come to realize that countless drugs work better in someone who’s fit or healthy. We know this is true for some supplements as well.
Fitter People, Finer Outcomes
HHN: Which drugs and supplements work better in healthier people?
MM: A large 10-year study of men and women on a cholesterol-lowering drug or statins of all types showed that the drug worked far better in the participants who were highly fit,"In 13 out of 16 clinical studies, exercise demonstrated a 5-point improvement in depression on average, compared to an average of 2−3 points improvement for prescription medication over placebo."and this group had an incredibly significant 70% reduction in death from all causes compared to the least fit group. A Duke University study, among others, found that prescription anti-depressants work better in individuals who also exercise. Exercise, by the way, has often been portrayed as influencing mild or moderate changes in those with depression, but a more recent Duke study of the literature found that in 13 out of 16 clinical studies, exercise demonstrated a 5-point improvement in depression on average, compared to an average of 2−3 points improvement for prescription medication over placebo. The ultimate synergistic treatment of depression includes both interventions.
It is possible that the threshold for supplement impact works the same way. Vitamin D is one example we know where this is true. When you lose weight or your cholesterol drops, the amount of vitamin D in the blood naturally increases, which lowers the amount of additional vitamin D your body needs to prevent bone loss. And, emerging research indicates that obesity or weight gain reduces the absorption of iron; losing weight allows iron levels to "naturally" increase.
The Mythic "Perfect Patient"
HHN: If someone is already practicing "perfect" lifestyle habits, is it necessary to consume any supplements?
MM: That’s a great question to which no one has a great answer, but there are some hints out there about what we should be doing, since perfect appears to be more perception than reality.
When the largest multivitamin trial ever conducted, "Physicians Health Study 2" with Centrum Silver, began, I thought Centrum was doomed to fail, because the average doctor participating in the 14,600-participant study was extremely healthy. I was wrong: Taking the multivitamin showed a modest benefit in preventing cancer in men and reducing the risk of cataracts in both men and women (in another Centrum trial)—and not only in the average participants, but also when researchers segmented out the healthiest folks in the trial, the ones eating 7 or more daily servings of fruits and vegetables. Centrum also corrected some nutritional deficiencies in the subjects in my opinion. So, some evidence exists that a multivitamin—specifically this multivitamin—could help healthy individuals.
But how many people are truly practicing "perfect" lifestyle habits? Research in America on this question has been very consistent over the past decade:"Alcohol consumption increases the risk of B-vitamin nutrient losses."Only 1−2% of the population is really doing everything possible in moderation and achieving those right health numbers that entitle them to be labeled the "perfect patient." Instead, people tend to grossly underestimate their health issues. Patients and audience members tell me all the time that they don’t need any pills, but they’re clearly overweight, drink too much, don’t get enough sleep, and/or have a poor diet. All these things impact nutrient levels.
Alcohol consumption, for one, increases the risk of B-vitamin (including folic acid) nutrient losses and is toxic in excess. I often hear, "I just have a drink a day," which would be fine, except when I ask patients to show me their serving of wine, it turns out to be equivalent to 2−3 servings.
On the other side of this you have the small percentage of people who are taking great care of their bodies and minds. Many of them consume large numbers of supplements, and they tend to give credit where credit is not due, attributing a host of benefits to the supplements.
Sometimes the real answer is the simple answer: Their diet and exercise habits are simply making them feel and be healthier.
To learn more about healthier living with supplements—how to select the right brands, the best times to take pills, what forms to use, and more—read "When Supplements Really Work, Part II: The Right Fit for Your Fitness."When Supplements Change Lives. Determining what you need. Click To Tweetby