This post was written by one of our AMAZING members, Dr Cristina Plemmons, PharmD, BCPS.  Cristina is a pharmacist at the Ralph H. Johnson VA medical center here in Charleston.  That happens to be where I get my healthcare, and I sure am glad there are people like Tina on staff!  You ready?  Lets get NERDY!

Have you ever gone to one of those chain supplement stores and felt the shelves were caving you in? How about the vitamin and supplement aisle of a grocery store or pharmacy? You could easily spend a small fortune stocking up on enough “boosters, energizers, muscle builders and stimulants” to fuel a small army, but will any of them even work for what you’re looking for? In the supplement world, it’s important to remember the simple concept that less is more. I’m even overwhelmed at the listing of supplements claiming to improve performance and I have a doctorate degree in medications and their use. I’ve tried to summarize the available evidence for you to consider when you look at what supplements to take regularly.

One important fact to highlight is that over-the-counter supplements are not regulated by the Food and Drug Administration (FDA) for safety and efficacy, like medications.¹ Basically, for a supplement to be on the market, there is no one ensuring that what the company says is in the supplement is actually in there, that it’s effective or that it’s being made in a clean or sterile environment. Also, there are not as many randomized, controlled clinical trials (the hallmark for evidence-based medicine, aka are the findings from a large group of people not explained by chance) for supplements. In order for medications to be approved for use, there are usually several stages of clinical trials to ensure the drug and dose is safe and effective for what the company claims. Anytime you take a medication prescribed by a physician, you can rest assured that it has been studied in thousands of people; but with supplements, there is not always that degree of reassurance. Of course, before you take any supplement or medication, you should consult with your primary care doctor (you know, the doctor everyone is supposed to have for their basic medical care).

1. Multivitamin

Did your mom ever make you stay at the dinner table until you ate your veggies? Turns out she was on to something with eating your veggies because many nutrients you need for general health and wellness can be obtained through diet. But when you have concerns about meeting those Recommended Daily Allowances (RDAs) as outlined by the National Institute of Health², a multivitamin comes in handy. Individual components of multivitamins vary by intended consumer (based on age, gender) and brand. My general recommendation is to utilize a brand that is certified by the United States Pharmacopeia (USP), which is an independent organization that verifies quality and purity standards for supplements³. This is considered a “gold standard” because supplements are not tested or regulated by the FDA.

Multivitamins are recommended for special groups of people to ensure they received enough vitamins and minerals. These groups of interest include pregnant women (or women of child bearing age), elderly (considered to be 65 years or older) or those with intestinal absorption issues (ulcerative colitis, Crohn’s disease, short gut, etc) or at risk for nutrient deficiencies (mainly those with a poor diet)⁴. Multivitamins are generally well-tolerated, but be careful of those that contain iron. Iron often causes abdominal pain, stomach upset and constipation. It can also turn your stool dark, which may look like you are having a stomach bleed. Also, if you have young kids or pets in your home, iron can be very harmful if consumed in large quantities. Chances are if you really need an iron supplement, your doctor will tell you and I would recommend taking it separately from a multivitamin because there are various kinds of iron and some are easier on your stomach than others!

There are four vitamins that I caution taking too much of: vitamins A, D, E and K. These are considered fat-soluble in your body and can build up in your fat (because most people have a lot of it) and cause toxic effects, as opposed to water soluble vitamins (like B and C) that your body will just get rid of (aka pee out) if you don’t need it. Ever take a B complex vitamin and see your pee turn neon yellow? You can overdose on vitamins A, D, E and K so do not exceed the RDAs listed on the bottle.

Overall for most people, the potential benefit of a daily multivitamin exceeds the potential risk (as long as you pick a good one) so it’s considered generally safe to include this in your list of daily supplements.

2. Fish oil

In more recent years, fish oil has turned in to a “trendy” supplement for anyone that is health-conscious to take, and for good reason. It’s probably one of the most studied supplements on the market. Fish oil contains two types of omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3’s are essential to help balance the omega-3 to omega-6 ratio we take in, especially because our diets are typically higher in omega-6, which is believed to be proinflammatory (or cause more inflammation throughout). Fish oil helps work in the stress signaling pathway of your body (aka how your body communicates with all the organ, blood, and hormone systems) by generating anti-inflammatory signals, which is the basis for its use in inflammatory states (such as pain or cardiovascular disease)⁵.

Fish oil has been at the center of many studies about cardiovascular disease, obesity and brain function. However, for our purposes, we will focus in on its role on inflammatory markers and muscle soreness. A common theme with studies for these reasons shows that cellular markers (helloooooo biochemistry class) of inflammation are improved in those that took fish oil, but patient centered outcomes (like subjective scoring of inflammation/soreness and markers of exercise performance) and biological markers of inflammation are not statistically significant compared to people that did not take fish oil^6,7. The scientific community generally believes that fish oil has a beneficial impact at the cellular level based on what we know about chemical structure and the body, but this may or may not be seen in the “big picture ocean” level (get it?) to make a difference or not for how people feel.

Fish oil is typically dosed based on the DHA component. Dosing ranges vary, but the American Heart Association recommends 1 gram daily total of fish oil (combined EPA + DHA). The general dose recommended for muscle soreness is 6 grams per day (typically split up to be 2 grams three times daily for ease of administration)⁷. Some people complain of “fishy burps” and this is usually lessened by taking fish oil with food. If you have a hard time swallowing the large capsules because of taste, you can put the bottle in the freezer to make it easier to stomach. Some people prefer the liquid form of fish oil, just make sure the container seals completely or else the oil could get a nasty smelling funk. Potency and purity are a huge area of debate in fish oil (wild caught vs farm-raised, what body of water the fish were caught in, etc) so stick to USP certified brands. Because of where fish oil works in your body, it can cause you to bleed or bruise more easily and potentially interact with some medications you are taking.

For most people, the potential benefit often outweighs the potential risk of taking fish oil. The group of people that may get the most benefit are those that also have a significant cardiovascular risk (heart history, strong family history of heart problems, high cholesterol despite a healthy diet) or those with chronic pain.

Honorable Mention: Krill Oil

Krill oil is also a fishy omega-3 source associated with the crustacean family of krill, but is considered more potent than fish oil because it’s in the phospholipid form (again with the biochemistry, instead of the triglyceride form in fish oil). For example, if you would normally take 6 grams/day of fish oil, the equivalent dose of krill oil would be about 4 grams/day. It’s also better absorbed in the body than fish oil (fancy word: bioavailable). The doses used in clinical trials range from 1-3 grams/day. This may sound like the better option but many people have a hard time taking krill oil because of the price and taste (it loses some potency if it’s frozen to make it easier to swallow, unlike fish oil).

3. Magnesium

One specific mineral that is typically only in very low doses in a multivitamin is magnesium. Unfortunately, this mineral is typically low in the Western diet, so often requires supplementation to meet recommended daily consumption values. Some people have medical conditions that need to have their magnesium closely monitored (if they’re on a medication that impacts magnesium in their blood, anyone with a heart arrhythmia or have had bowel surgery). It’s important to talk to your doctor about taking magnesium because if the magnesium level in your blood is too high, it can cause serious health issues.

The most desirable effects of magnesium are for potential benefits on sleep and blood pressure^8,9. There are only a few studies that investigate its effect on muscle oxygenation and aerobic exercise, but their results are promising for a beneficial effect. Magnesium is sedating (makes you sleepy), so many people use that side effect to their advantage to take the magnesium before they go to sleep. Magnesium has been shown to help lower blood pressure when the person’s baseline magnesium level is low or their blood pressure if elevated (over 140/90, which is considered high blood pressure). Magnesium has not been associated with reducing muscle cramps, which is what it’s commonly believed to be used for.

There are different forms of magnesium supplements. One of the most common side effects is diarrhea. Magnesium citrate is a liquid laxative that is sometimes used for bowel preparations before procedures because of its fast-acting induction of diarrhea. Fun fact: if you are ever constipated and need to go ASAP, drink a bottle of magnesium citrate when you are in the bathroom, ready for showtime – it won’t disappoint. Magnesium hydroxide (milk of magnesia) is a laxative as well. These laxative forms should not be used on a regular basis and are not the right forms to take for regular supplementation.

Magnesium oxide (commonly known as “Slow-Mag”) is more of a gentle, slow release magnesium supplement and is what is recommended for daily use. Magnesium gluconate is also a daily supplement that is generally a little easier on your stomach. Some people prefer to mix magnesium powder in to water and drink it. There is no benefit to taking it dissolved in water or taking it in pill form. Typical dosing when taken as a daily supplement is 200-400mg/day at bedtime.

Those that will likely benefit the most from magnesium include those that have a hard time sleeping or those with slightly elevated blood pressure or low serum magnesium levels from bloodwork. There is more risk of potential harm this with supplement if use inappropriately or without monitoring so definitely discuss with your doctor first.

Another common form of magnesium is Epsom salts, which is magnesium sulfate. Your mom may have had it all wrong when she told you to take an Epsom salt bath (after you ate your veggies at dinner of course), because the science behind this being beneficial for pain or muscle soreness, is mostly nonexistent. Adding magnesium to your bath may make it slightly easier for you to float (because it changes the specific gravity of the water) but scientifically, the salt can’t cross in to your body to make much of a difference. The beneficial effects from an Epsom salt bath is probably more associated with the warmth of the bath, than the salts.

4. Protein

Whey protein has gained a lot of attention in the past decades as a source of convenient and quickly absorbed dietary protein to help people achieve their daily protein intake goals. Whey itself has no magic ingredients, but rather helps you get in the appropriate weight-based protein quantity each day. The two proteins that come from cow’s milk are whey (absorbed quickly as it’s the water-soluble form) and casein (the curds). Whey protein itself is composed of many different peptides; think about the protein being a Lego structure and the peptides being different colors of Legos to help build the structure. For simplicity sake, I won’t dive in to casein protein or plant-based proteins, but just know that it there are other options that some people can take.

There have been a lot of studies that have utilized whey protein, but the effects seen are likely more related to total protein intake, as opposed to the whey protein itself. It’s widely accepted and established that whey protein can help increase muscle protein generation (synthesis)¹⁰. Most studies have a hard time confirming the effect of the supplement itself, even if ‘double blinded’ compared to a sugar pill (placebo).

There are a lot of important factors to consider when looking at what kind of protein to purchase. The first includes which variant of protein the buy. The two most common are whey concentrate and whey isolate, which differ based on how much of the product is actual whey protein. Isolate is 90% protein by weight, whereas concentrate has a wide range (35-80% protein by weight) and is considered less ‘potent’.

Another major factor to consider is when to take your whey protein. It has been found that ingesting protein around the time of exercise stimulates protein synthesis to a greater extent than if you ingest the protein over a longer period during the day (we’re talking 2-3x increase in generation)¹¹.

Overall, whey protein is a good supplement to use with minimal side effects. Protein is an essential macronutritent that is needed in your diet, and whey protein is an easy, well-tolerated form that can help you achieve that goal. The main take home point is just make sure you get a quality protein and take it at the right time!

5. Creatine

I’ve saved the best for last: creatine. I’ll admit I’ve had a personal bias against creatine for a long time, and my feelings are shared by many health care providers. This fear likely stemmed from really a theoretical claim for potential harms. Back to biology class: creatine is made naturally in the body (stored mostly in the muscle, but smaller amounts in kidneys, liver and brain). Creatine is stored in your body as phosphocreatine which helps make ATP (remember the Krebs Cycle?), which adds to your body’s gas tank of easily accessible energy to do work. One of its’ byproducts (creatinine) is a surrogate marker that is measured in the blood and urine as a marker of kidney function. To a pharmacist, the kidneys are the gate keepers to any medication as the kidneys get rid of all waste products (and most medicines), so—pretty important and you want to protect this little guys at all costs. Stay with me now: by taking in more creatine, this can artificially increase your excretion of the waste product, which can essentially make it look like your kidneys aren’t functioning well in lab work. Also, there is a myth that creatine causes dehydration because it drives more of your body’s water in to the cells (as opposed to being “free” in your body) which can also hit the kidneys, especially if you’re working out and sweating.

So I’ve swallowed my pride and dug in to the literature and realized that the myths about creatine are really untrue. Creatine is probably the most studied over-the-counter supplement on the market so rest assured – this stuff has a low likelihood for harming you. The International Society of Sports Nutrition (ISSN) also noted in their position statement: “Creatine monohydrate supplementation is not only safe, but possibly beneficial in regard to preventing injury and/or management of select medical conditions when taken within recommended guidelines.”¹² It also goes on to state there’s no evidence of harm from this supplement when taken by otherwise healthy individuals.

One side effect that does occur is weight gain and some people can have stomach upset. Though the reports of kidney and liver dysfunction are mainly from case reports (some of the lowest levels of evidence in the scientific world and considered ‘rare’), I would caution those with underlying kidney dysfunction as well as those sensitive to fluid changes (people with liver failure or heart failure) to definitely check with your doctor about using creatine. Regardless, if you are going to take creatine, it’s just important you pay attention to how much water you’re drinking and drink a little bit more while you’re using it.

Now we know it’s relatively safe, but does it work? The highest level of scientific evidence we have includes meta-analyses. One large meta-analysis looked at 22 randomized controlled trials that studied the effect of creatine (compared to sugar pill) on muscle strength and performance weightlifting through resistance training. This analysis found that on average, those that took creatine had an 8% higher increase in muscle strength (1, 3 or 10 rep max) than those that took the sugar pill. Also, in terms of weightlifting performance (max reps at a particular percentage of weight), those that took creatine had a 14% higher improvement than those that just took the sugar pill. This review also found that the exact improvement in each outcome was highly variable.

Bust out your calculators to determine what dose of the creatine you should use (I’ve seen some of you try to do barbell math). It’s been studied using a “loading protocol” which means you just have to take a higher amount of it at first to “saturate” your body until it achieves what us science nerds call steady state (essentially where equal amounts of it are in your body at any given time). For the first three days, ISSN recommends ingesting 0.3mg per kilogram of body weight per day. For example, for a 75kg person (165lb), the initial dose would be 75×0.3=22.5grams per day. Then, the standard maintenance dose is 3-5grams per day. You can take in a lower quantity per day (mainly if you have stomach upset), it will just take longer for your body to increase the muscle stores of creatine. Another commonly studied dose is 0.3grams per kilogram body weight per day for 5-7 days (loading dose), followed by 0.03grams per kilogram per day (maintenance dose). It’s really a tasteless powder that can be mixed with any liquid and just drank quickly.

In summary, creatine is one of the most widely studied, cheapest, most well tolerated supplements out there for those that want to improve their muscle mass and power output.

These five supplements are just a drop in the bucket compared to all of the supplements available on the market. No matter which supplement you choose to take or not to take, I recommend you make that decision intentionally with your goals in mind and never be afraid to ask your doctor (or trusted pharmacist) if it’s safe or effective.

References:

1. US Food and Drug Administration: Information for consumers on using dietary supplements. Accessed web 22 May 2018. https://www.fda.gov/Food/DietarySupplements/UsingDietarySupplements/default.htm
2. National Institutes of Health, Office of Dietary Supplements. Nutrient recommendations: dietary reference intake. Accessed web 22 May 2018. https://ods.od.nih.gov/Health_Information/Dietary_Reference_Intakes.aspx
3. United States Pharmacopeia. Dietary supplement reference standards. Accessed web 22 May 2018. http://www.usp.org/dietary-supplements/reference-standards
4. National Institutes of Health, Office of Dietary Supplements. Multivitamin/mineral supplements. Accessed web 22 May 2018. https://ods.od.nih.gov/factsheets/MVMS-HealthProfessional/#h6
5. National Institutes of Health, Office of Dietary Supplements. Omega-3 fatty acids. Accessed web 22 May 2018. https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/
6. Pot GK, et al. No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-aged individuals. Eur J Clin Nutr. 2009 Nov; 63(11): 1353-9.
7. Bloomer RJ, et al. Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced inflammatory and oxidative stress biomarkers: a randomized, placebo controlled, cross-over study. Lipids Health Dis. 2009 Aug 19; 8: 36.
8. Hatzistavri LS, et al. Oral magnesium supplementation reduces ambulatory blood pressure in patients with mild hypertension. Am J Hypertens. 2009 Oct;22(10):1070.5.
9. Nielsen FH, Johnson LK, Zeng H. Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnes Res. 2010 Dec;23(4):158-68.
10. Pennings B, et al. Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am J Physiol Endorinol Metab. 2012 April 15;302(8)E992-9.
11. Moore DR, et al.Resistance exercise enhances mTOR and MAPK signalling in human muscle over that seen at rest after bolus protein ingestion. Acta Physiol (Oxf). (2011)
12. Buford TW, et al. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr. 2007 Aug 30;4:6.