Not only is it important to know what a dietary supplement contains and how it might affect your body, it is critical to be aware of how it might interact with other supplements or conventional foods that are being taken at the same time. Below are some examples of how “stacking” supplements may not lead to the desired effects.

Antagonism: 1+1=0
In some cases, the effects of one supplement may actually negate the effects of another when the two are taken together. Theoretically, the net result would be that neither supplement is effective. However, the net result often sees the effects of one supplement diminishing, while the effect(s) of the other supplement remain unknown.

Here are some examples of Antagonism:

1. Soy protein inhibits the absorption of iron. Therefore, the effects of taking both supplements simultaneously may negate the effects of taking the iron supplement in the first place.

2. Normal levels of calcium supplements that are taken concurrently with an iron-rich meal or an iron supplement can inhibit iron absorption. Therefore, the use of calcium supplements may hinder iron absorption/status if the two are taken together.

3. Increasing the intake of magnesium may also reduce phosphate absorption. Magnesium intake exceeding 500 mg/day can negatively affect the balance of phosphate. Therefore, taking a magnesium supplement may interfere with the desired effect(s) of a phosphate supplement.

4. Excess chromium has been suggested as a factor in impairing iron transport ability. Therefore, taking a chromium supplement may interfere with the desired effect(s) of an iron supplement. This may carry over to a decline in aerobic capacity or fitness. Avoid taking chromium and iron supplements together.

5. Excessive iron intake may interfere with the absorption of zinc. Therefore, taking an iron supplement may counteract the desired effect(s) of taking a zinc supplement at the same time.

6. Zinc can inhibit the absorption of other minerals, especially copper. Chronic (>6 weeks) consumption of zinc supplements, in excess of 50 mg/ day, has been linked to copper deficiency in humans. If feasible, ingest zinc at night, on an empty stomach to prevent it from interfering. Copper intake should be increased if elevated zinc consumption lasts for a number of days.

7. Fiber can interfere with zinc absorption. Although nuts, legumes and whole grains are good sources, the high level of fiber in these foods can decrease zinc absorption. Therefore, avoid taking fiber and zinc supplements together.

Synergism: 1+1=3
Synergism is the joint action of two parts so that their combined effect is greater than the algebraic sum of their individual effects. Most consumers would view this as a positive effect. More bang for the buck. However, the fact that something is good does not guarantee that more is better. In fact, when the supplement is more eccentric, such as one that proposes to boost the body’s natural production of testosterone, the effects may be unwanted, and in some cases, detrimental.

Here are some examples of Synergism:

1. Vitamin C enhances the absorption of iron by preventing the oxidation of ferrous iron to the less absorbable ferric form. Therefore, taking a vitamin C supplement together with an iron supplement may enhance the function of iron. Ingest iron between meals with good sources of Vitamin C (orange juice, strawberries, tomatoes) to increase its absorption.

2. Co Q10 is fat-soluble, so it is best utilized when dietary fat is available. Combining them with sources of fat may enhance the utilization of Co Q10.

3. Phosphate is absorbed best when calcium and phosphorus are ingested in approximately equal amounts. Since Vitamin D must be present for efficient calcium absorption, a combination of Calcium, Phosphorus and Vitamin D appears to be synergistic.

Potentiation: 1+1=10
Potentiation is similar to synergism, but to a much larger degree. The combined effect of two products far exceeds the sum of their individual effects. This type of chemical reaction could be dangerous when there are toxicity effects of a particular ingredient.

Some examples of Potentiation include:

1. Consuming ginseng with caffeine may cause over-stimulation and an upset stomach. This stacking effect is also identified as an advanced level of Synergism because the extent of the adverse effect(s) have not been quantified.

2. It has been suggested that to get the most out of ZMA, it should be used in combination with (i.e. “stacking”) Terrestris and Androstenediol. Androstenediol is a prohibited substance. This stacking effect is also identified as an advanced level of Synergism because the extent of the effect(s) have not been quantified.

3. In addition, if ZMA does, in fact, enhance testosterone levels like the Western Washington study suggests, athletes must be aware of the consequences related to drug testing. This stacking effect is also identified as an advanced level of Synergism because the extent of the effect(s) have not been quantified.

4. It has been suggested that supplementing with ribose enhances the effects of creatine.

5. Phosphate supplements in conjunction with creatine supplements may create a synergistic environment.

Effects Involving Foods and Supplements
In addition to combining supplements, there are other factors involving food, exercise and/or medications that can impact the desired effect(s) of a supplement. In some cases, multiple vitamins and/or minerals are necessary for proper digestion and absorption. For example, in order for calcium to be absorbed, vitamin D must be present. So calcium-containing products, including foods, often contain vitamin D. Likewise, Vitamin B6 is involved in the absorption of Vitamin B12. So Vitamins B6 and B12 often occur together in multi-vitamins as well as foods. But most of the scenarios below would be considered antagonistic in the sense that the results can be just plain detrimental to performance and/or health.

· Too much magnesium (ie. 500 mg/day) can cause gastrointestinal disturbances, such as diarrhea.

· Zinc supplements (160 mg/day) can decrease HDL-cholesterol, also known as “good” cholesterol. Taken in amounts as small as 17-50 mg/day can prevent the increase in HDL-cholesterol that exercise is supposed to cause.

· Copper intake of 10-15 mg/day can cause nausea, vomiting and diarrhea. Intakes exceeding 20 mg/day can lead to toxicity.

· High protein diets and high phosphate foods (meat, dairy products and soft drinks) stimulate the body to rid itself of calcium via urine and stool. Therefore, using a soft drink to wash down a calcium supplement may be counter-productive. Likewise, the effects of the calcium supplement may be hindered by eating too much meat or dairy. Note-This does not mean that low protein diets are better. Each day, athletes should eat 1.4-1.8 grams of protein for every kilogram they weigh.

· There are certain disadvantages to increasing dietary Branched Chain Amino Acid (BCAA) intake without making the relative adjustments to the other energy-yielding nutrients (carbohydrate and fat). An increase in BCAA metabolism increases the production of TCA-cycle intermediates. This increases the cycle’s interaction with pyruvate, which in turn promotes an increase in the rate of glycolysis. As the rate of glycolysis increases, the body is exposed to a greater risk of glycogen depletion. An increase in carbohydrate intake may help prevent this glycogen depletion, but be sure to keep the other nutrients (protein and zinc) in the diet as well. They are critical in maintaining immune response, and substituting them for carbohydrate may negate the desired effect.

· In order for calcium to be absorbed, vitamin D must be present. So calcium supplementation is usually in conjunction with vitamin D supplementation (400 IU/day). If dietary vitamin D intake is inadequate, the calcium supplement may not work at all.

· Diets high in fat and too low in carbohydrate tend to increase carnitine excretion. In addition, too much protein increases the glomerular filtration rate, which in turn increases carnitine excretion. This also negates the desired effect(s) of a carnitine supplement.

· Stress seems to promote chromium loss. Increasing simple sugar intake, strenuous exercise, and physical trauma can promote chromium depletion.

· Creatine supplementation appears to be ineffective when a person’s initial total creatine concentration is high (>130 mmol/kg DM-dry muscle).

· Creatine appears to be ineffective when the short-term (<7 days) dose is low (<20 g/day).

· Creatine appears to be ineffective when the term of a high dose (20-25 g/day) exceeds 7 days.

· Creatine appears to be ineffective when the term of a low dose (3-5 g/day) is less than 14 days.

· Creatine appears to be ineffective when the maintenance dose (2-3 g/day) is discontinued for more than 4 weeks.

· Creatine appears to be ineffective when it is not accompanied by carbohydrate (ex. 370 g in solution for a 20 g/day dose).

· Creatine appears to be ineffective when it is not accompanied by exercise (i.e. training).

· Creatine appears to be ineffective when the quality and quantity of the training performed during supplementation is not maximized.

· Creatine appears to be ineffective when the performance exercise tested is a single bout versus a set of repeats.

· Creatine appears to be ineffective when the duration of the recovery period between repeats is less than 30s or greater than 5 minutes.

· It has been suggested that vegetarians would display the greatest creatine supplementation effects. This would be due to the presumably low initial levels of total creatine as a result of not eating meat, fish or poultry (natural sources).

· Sprint training also increases the creatine phosphate content of muscle. So, sprinters tend to have higher muscle creatine levels than distance athletes.

· Long-term use of ginseng may cause menstrual abnormalities and breast tenderness/soreness in some women.

· For athletes whose plasma glutamine levels are below normal (i.e. below 0.5 mmol/L), adding approximately 20 g/day of protein in the form of food, such as meat and cheese, can increase plasma glutamine levels. However, one must be cautious, as research also suggests that diets high in protein and low in carbohydrate can actually lower plasma glutamine levels by as much as 25%! Unnecessary large increases in dietary protein intake can be just as harmful as consuming too little. The recommended intake for protein is 1.2-1.4 g/kg of body weight per day.

· Avoid iron supplementation when an iron deficiency is not present. Excessive ferritin can stimulate increased oxygen free radical reactions possibly leading to tissue damage.

· Coffee and tea consumption impair iron absorption.

· Coffee contains caffeine, but the other ingredients in coffee may actually blunt the body’s physiological response to that caffeine. Therefore, getting caffeine from coffee may actually negate the intended effect(s) of the caffeine.

· The consumption of carbonated beverages may adversely affect the calcium-to-phosphorus ratio.

· Vitamin B12 helps in the formation and regeneration of red blood cells, ultimately helping to prevent anemia.

· Mixing taurine (a supplement added to many energy drinks) with alcohol can lower blood sugar, increase blood pressure and/or cause heart attack.

Conclusion
The stacking scenarios described in this article are the ones we actually know about. Given the astronomical number of dietary supplements on the market today and the variability among products, the number of potential stacking combinations becomes extremely high. Without knowing the effects of these combinations of supplements, it is impossible to advise and make clear and valid recommendations about them. For this reason, athletes are advised to obtain as many of the required nutrients as possible from a diet that consists primarily of conventional foods in quantities that have been recommended for their individual training scenario.

Recommended Reading:

Risky Dietary Supplements - A roundtable discussion with Priscilla Clarkson, PhD, Ellen Coleman, MPH, MA, RD and Christine Rosenbloom, PhD, RD, LD. Ref: Sports Science Exchange Roundtable 48, Volume 13, Number 2 (2002).

Nutritional Supplements and Doping – An overview of by Andrew Pipe, MD (member of the FINA Doping Control Review Board) and Christiane Ayotte, PhD (from the Laboratiore de Controle de Dopage in Quebec, Canada). Ref: Clinical Journal of Sport Medicine, Volume 12, Pages 245-249 (2002).