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Whenever I evaluate the evidence for a dietary supplement, one of my first questions is “What is it?” I remember many years ago, when I first started doing this, I looked up the ingredients for a product advertised to cause weight loss. One of the ingredients was listed in the Natural Medicines Comprehensive Database as causing weight gain! Ever since, I have been very suspicious of the reasoning for including ingredients in a multi-ingredient product.

I recently wrote about SeroVital, a dietary supplement advertised to boost the body’s own production of human growth hormone (HGH). I found that Dr. Oz had recommended supplements with these four amino acids: glycine, ornithine, arginine, and lysine. SeroVital only contains two of these. And in addition, SeroVital contains the powdered herb Japanese catnip (Schizonepeta tenuifolia). Why did they pick different amino acids than Dr. Oz did? And why on earth did they add the herb? It “appears to have some selective anti-inflammatory effects”, but no other scientifically supported uses. An article on Chinese herbs says it is useful for treating colds and flu and dispelling “wind”. I found no evidence that it increases HGH or has any anti-aging effects. How do you suppose the designers of SeroVital imagine that it adds to the effectiveness of their product?

I also came across a product on PatchMD that makes anti-aging claims for vitamins A, C, D, B3, B6, B9, curcumin, clove extract, ginger root extract, Indian gooseberry extract, L-carnitine, CoQ10, resveratrol, choline, glutathione, NAC, and alpha-lipoic acid. It combines all of these in a convenient Anti-Aging Topical Skin Patch, supplying the nutrients via the skin. They claim all these ingredients are backed by science for their anti-aging effects, but that’s a real stretch, based mainly on their antioxidant and anti-inflammatory properties. At least they provided a proposed (pseudo-)scientific rationale.

Why do the makers of Lipo-Flavonoid imagine their mixture will cure tinnitus? It contains lemon bioflavonoid complex, vitamins, choline, inositol, and melatonin. There’s no scientific evidence; did they rely on unreliable testimonials from friends and family?

Then there’s Super Brain Renew, a nootropic designed to improve memory, focus, clarity, and mood. It contains the “essential 5” brain supporting nutrients (DHA Omega 3, Huperzine A, Phosphatidylserine, Bacopa Extract, and N- Acetyl L-tyrosine). But essential isn’t enough for them. They add vitamins A, C, D, E, B-1, 2,3,5, and 6, folic acid, biotin, calcium, iron, magnesium, zinc, selenomethionine, copper, manganese, chromium, molybdenum, potassium, and 692 mg of a proprietary blend of 19(!) other ingredients (herbs, minerals, green tea extract and much more). Another product, Mind Lab Pro, contains only a few of these nutrients but contains several others, including citicoline, lion’s mane mushroom, maritime pine bark extract, Vitamin B12, and others. Are they going by the principle “more is better?” Do they think the sheer number of ingredients will impress customers? How do you suppose different nootropics intended for the same purpose came up with such different lists of ingredients?

How do they decide?

I see this kind of thing everywhere. Actually, most dietary supplements contain single active ingredients; but a great many of them are a potpourri of vitamins, minerals, and herbs. I can’t understand how they choose which ingredients to put in their products. My imagination runs wild. Did they throw in some vitamin B9 just because they needed to use up an overstock they had left over from a previous product? Did they ask unqualified people to brainstorm, put all suggestions on a dartboard and throw darts at it? Did they rely on intuition or dreams? Did they use a pendulum or dowsing rod? Did they disagree and ask the janitor to arbitrate? Did they go by the cost of each ingredient (“That one’s cheap, and it wouldn’t hurt to throw some in”)? Did they consider side effects or interactions with other medicines? If they want antioxidants, why did they pick those specific ones and not others? I can imagine all kinds of bizarre scenarios, and I’m sure you can too.

I don’t for an instant imagine that these decisions are based on good scientific evidence, but people seldom do things for no reason at all. They probably have some rationale to justify their choices in their own minds. I wish I knew what that rationale is. I would dearly love to understand their thinking. Oh, to be a fly on the wall during their planning sessions! While it would be unlikely to impart any useful information about the ingredients themselves, it could be highly entertaining and could give insight into human behavior. And it might reveal which companies actually believe in their products and which are made up of crooks who deliberately sell products for the sole purpose of making money by deceiving the public.

Multiple ingredients are sometimes reasonable

That’s not to say multiple ingredients are never justified. Here are some of the reasons science-based doctors might want to combine drugs:

  • One might not be very effective, and two might have an additive effect (2 + 2 = 4).
  • There might be a synergistic effect where 2 + 2 = 5, but synergy is nowhere near as common as proponents of natural medicines seem to believe. When a mixture of ingredients or a plant extract is tested head-to-head against a single active ingredient, the single active ingredient usually works just as well. And it might even work better because of unwanted ingredients in the plants.
  • If drugs have toxic side effects, combining drugs might allow a reduction of the dose of each to avoid toxicity.
  • If a patient is deficient in a nutrient, the treatment might be more effective after correction of the deficiency. But there would be no benefit to adding more of the nutrient for patients who were not deficient.
  • Drugs can be prescribed separately, but combining them to reduce the number of pills can improve convenience and compliance.

When ingredients are combined, there is no guarantee that the combination will work better, and there is always a possibility that the combination might have unexpected effects. If there is an adverse reaction to a combination, it can be difficult to identify which ingredient is responsible.

Conclusion: Buyer beware

We should always think critically about claims for any treatment, and we should always ask for the evidence; but dietary supplements that combine multiple ingredients are particularly suspect. The only reliable way to find out if a treatment is safe and effective is to test it in controlled clinical studies. Scientific testing is expensive; but it might lead to FDA approval, so the products could be marketed as drugs rather than as dietary supplements. In the absence of adequate evidence, taking dietary supplements is a gamble, especially since some products have been found to contain contaminants like heavy metals, toxins, and even prescription drugs.

I can’t stop wondering why they chose each ingredient. I would dearly love to be that fly on the wall! But then a fly couldn’t tell anyone what it heard.

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Posted by Harriet Hall

Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. She received her BA and MD from the University of Washington, did her internship in the Air Force (the second female ever to do so),  and was the first female graduate of the Air Force family practice residency at Eglin Air Force Base. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS (Director of Base Medical Services) and did everything from delivering babies to taking the controls of a B-52. She retired with the rank of Colonel.  In 2008 she published her memoirs, Women Aren't Supposed to Fly.