When considering a daily multivitamin, it is important to choose one that is well balanced, bioavailable, and contains high-quality ingredients.  When considering Hardy Nutritionals® micronutrient formulations Daily Essential Nutrients or Optimal Balance, you might be surprised at first to see such a wide variety of percent daily values (%DV) on the label, and some of the percentages are pretty high!  If you have ever wondered about the safety implications of these quantities of nutrients, this article is for you.

The %DV (percent daily value) on the supplement facts label displays the percent of the recommended daily intake that the product delivers in each serving.  The %DV is based on the RDA (Recommended Dietary Allowance, now called the Reference Daily Intake or RDI) or the AI (Adequate Intake - for nutrients without an established RDI).  The RDA/RDI is defined as the “average daily intake level that is sufficient to meet the nutrient requirement of nearly all (97 to 98 percent) individuals.” This means that 2-3 percent of individuals may have higher minimum nutrient requirements.  It is important to note that “intake at the level of the RDA or AI would not necessarily be expected to replete individuals previously undernourished, nor would it be adequate for disease states marked by increased requirements.”  

In short, the RDI (reflected in the %DV) is an estimate of minimum intake required to prevent outright deficiency for most people, and does not at all inform an evaluation of toxicity.  In estimating the higher end of intake, the Institute of Medicine also publishes a Tolerable Upper Level (UL) which is defined as:

• “the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects for almost all individuals in the specified life stage group.”
• “applies to chronic daily use.”
• “professionals should avoid very rigid application of ULs and first assess the characteristics of the individual…”
• “It is beyond the scope of this report to address the possible therapeutic benefits of higher nutrient intakes that may offset the potential risk of adverse effects.”
• “The UL is not meant to apply to individuals who are treated with the nutrient under medical supervision or to individuals with predisposing conditions that modify their sensitivity to the nutrient.”
  
  

The doses of vitamins and minerals in Optimal Balance and Daily Essential Nutrients are nearly all well within the safe range of intake for adults (i.e. well above the RDA and well below the UL). The only ingredients found in Hardy's broad-spectrum micronutrient formulations which exceed the Tolerable Upper Level are niacin, zinc, and magnesium, and below we address why this is still incredibly safe.

Niacin: The UL for niacin in the United States is 35 mg/day.[1]  The "adverse event" which is cited as the reason for this UL is the flushing effect of nicotinic acid.  However, our formulations use niacinamide, which is a non-flushing form of niacin.  In other jurisdictions (e.g. EU & Australia) the ULs for niacinamide and nicotinic acid are appropriately separate.  The European Union sets a tolerable upper limit of 900mg/day of niacinamide - fully ten times the dose in 12 capsules of our clinical strength micronutrient formulation, Daily Essential Nutrients. [2]  As the form of niacin we use is, in fact, the non-flushing form, we are confident that the levels of niacinamide offered in both our general health and clinical strength products are safe.

Magnesium: The UL for magnesium is 350 mg/day, based on the adverse event of potential diarrhea in some sensitive individuals[1]. However, this value is clearly not intended to limit dietary intake as the recommended intake for adult males is 420 mg/day!

For a variety of reasons we are able to deliver 600 mg of magnesium in 12 capsules without causing diarrhea in almost any case among tens of thousands of supplement users; there is a slight loosening of the stool for some users, but we almost never see diarrhea attributable to DEN alone.  One reason for this is that we recommend divided doses throughout the day - each only 200mg - which is well below the UL.  Another reason is that the ULs are set very conservatively so as to apply to the most sensitive of individuals, but many people can ingest well above the established UL without experiencing any adverse events. 

Finally, our broad-spectrum micronutrient formulations also contain a large quantity of calcium, which tends to be constipating when taken in isolation.  Taken together, the competing bowel tolerance effects of calcium and magnesium sort of "cancel each other out" neither overly firming nor overly loosening the stool.

Zinc: The UL for zinc is 40 mg in adults, and 12 capsules of DEN delivers 48 mg. This dose of zinc is safe due to the balancing presence of copper in our micronutrient formulations.

In the Dietary Reference Intake publication on zinc, the Institute of Medicine expert panel concludes that "The adverse effect of excess zinc on copper metabolism (i.e., reduced copper status) was chosen as the critical effect on which to base a UL..." [3]   While there are many other known nutrient-nutrient interactions, this is one of the few that is specifically referenced as a critical determinant for setting intake recommendations.  This is because a large body of very consistent data confirms that chronic intake of high levels of zinc, when taken alone, can depress copper status, even leading to indicators of outright copper deficiency over time. 

Because all the Hardy Nutritionals® products that contain zinc also contain a balancing amount of copper, the likelihood of causing copper deficiency is next to none, and the reason for which the UL was set becomes nearly irrelevant.  Further reassurance for the safety of the level of zinc in Daily Essential Nutrients, is the fact that the Lowest Observed Adverse Event Level (LOAEL) from which the UL was extrapolated was determined to be 60 mg/day.  In other words, the UL of 40 mg/day was conservatively set to be a full 20 mg/day lower than the amount known to induce any hint of toxicity. It is worth noting that most of the Tolerable Upper Levels have similarly conservative "uncertainty factors" built into the recommendation, resulting in ULs which are generally well below the levels known to be toxic from peer-reviewed scientific studies. 

So is there any scientific evidence that the particular copper to zinc ratio in our clinical strength formula, Daily Essential Nutrients, is safe and effective in practice as well as in theory?  Yes.  There is a large body of data now supporting the observation that high levels of copper, especially relative to zinc, correlate with symptoms of many mood, behavioral, and developmental disorders, including ADHD. [4]  Consistent with this emerging understanding, low baseline serum copper correlated with positive outcomes in an RCT using a formula substantially similar to Daily Essential Nutrients in an ADHD population. [5]  As a result of this finding, copper status was evaluated more rigorously in the recently published double-blind study using Daily Essential Nutrients in children with ADHD.  No significant difference in serum copper status resulted from the children taking 12 capsules per day of Daily Essential Nutrients over the 10-week trial, and there was also no difference in overall copper status between the placebo group and the treatment group. [6]

While not everyone tolerates our supplements at therapeutic doses and outcomes vary based on a myriad of factors beyond the scope of any one single product, our experience is that many individuals have safely taken Daily Essential Nutrients and Optimal Balance for many years.  Stepping back from the scrutiny of individual nutrients and considering the broader landscape of essential nutrient supplementation, it is abundantly clear to most of those who have intensely studied micronutrient therapy that the safest and most effective way to supplement is to give a balanced complement of a broad spectrum of nutrients.

Hardy Nutritionals® micronutrient formulations, Daily Essential Nutrients, and Optimal Balance are considered safe for children and adults.  For more information, please visit our Frequently Asked Questions.

Sources:

[1] https://www.nap.edu/read/6015/chapter/8#142

[2]  Section 2.1.2.2. European Union Scientific Opinion on Dietary Reference Values for niacin

[3] https://www.nap.edu/read/10026/chapter/14#483

[4]  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661234/ & https://link.springer.com/article/10.1007/s12011-015-0395-3

[5]  https://www.sciencedirect.com/science/article/pii/S0278584613002935

[6] https://www.ncbi.nlm.nih.gov/pubmed/28967099

About Hardy Nutritionals®

Hardy Nutritionals® multivitamin-mineral products are powered by our proprietary NutraTek™ mineral delivery technology, which combines each mineral with specialized organic molecules—just like nature—to optimize absorption and distribution to body cells. Our flagship supplement, Daily Essential Nutrients, is widely considered to be the most research-backed micronutrient treatment.