At one time, drugs and therapies were highly unregulated. All you had was the good word of your doctor. Active ingredients varied from batch to batch, and side effects weren’t discovered until after you received your treatment. 

But starting from the 1930s, medical researchers began evaluating the claims behind different kinds of drugs and therapies. Researchers created a system known as a clinical trial to help standardize medicine, herbs, and supplements.

Clinical trials are research studies performed in people to determine whether a test or treatment is safe and effective. 

Two types of clinical trials.

1. Observational studies.

Observational studies involve monitoring people over time, investigating how their behaviors or actions possibly lead to some health outcomes.

2. Intervention studies.

Intervention studies involve exposing subjects to an intervention, like the ingestion of a supplement. Uncontrolled studies include only the intervention without a juxtaposed control or placebo group. On the other hand, controlled studies do involve either a control group or a placebo group for comparison.

A randomized, controlled trial (or RCT) is considered the “gold standard” of human research since it involves a control group, and subjects are randomly assigned to either the placebo or the studied intervention. Both researchers and subjects are blinded to the intervention's administration, meaning neither is aware of the group assignments. A blind study minimizes the risk of bias, securing the observed results as objective data.

Supplements vs. drugs.

Typically, clinical trials for drugs advance through four phases of testing, undergoing exorbitant cost. According to Nature Reviews Drug Discovery, the median expense for a single Phase Three drug trial is $19 million.

However, most studies for nutritional supplements don’t go past more than two phases of testing because they do not assess the prevention, treatment, or cure of an ailment.

How to arrange a clinical trial? 

Clinical trials require careful planning and review. To begin a clinical trial, you need a principal investigator, the person who oversees the research. The principal investigator is usually a scientist considered an expert in the field pertaining to the trial. They design the experiment and select a research team for the experiment.

Clinical trials also need sponsors who fund the experiment. Sponsors can range from government agencies to companies and non-profit organizations. Sponsors review the research plan that outlines the subjects to be studied in the trial, the measurements to be taken, and the schedule of procedures.

The IRB (Institutional Review Board) also needs to approve of the clinical trial before it begins. An IRB consists of people chosen by the health care center that provides the participants for the trial. Each IRB usually includes five members and must consist of one of the following: 

• one scientist, 

• someone who’s not a scientist, and

• someone who’s not from the health care center.

Each IRB reviews the available data to assess the safety and potential risks of testing the substance in humans. Most new substances must pass substantial preclinical safety testing in an IRB review before they are approved for use in humans. 

Key questions to consider when reviewing the clinical trials for supplements.

Clinical trials can be hard to decipher. Here are some criteria you can review a supplement’s merit behind its advertised clinical trials:

1. Did the clinical study conduct a randomized, controlled trial (RCT)? 

Was there a control or placebo group in the trial? Were both the subjects and researchers blinded, meaning were they aware of which subjects received a placebo and which ones received the supplement? These parameters are essential to determine the objectivity of the clinical results. 

2. Did the results of the clinical trial show statistical significance?

Statistical significance helps quantify whether a trial result is likely due to chance or due to the real effect of the studied supplement. Usually, the larger the sample size, or power of the study, the less variability you have to contend. The greater the variability with subjects or between subjects to a given intervention, the more difficult it is to show a statistical difference. 

3. What was the size or duration of the study?

Speaking of sample size, the best way to maximize your statistical significance is with a longer duration of time and a larger sample size in your test. Checking the number of subjects involved and the length of a study is an excellent way to find if the clinical trial was more or less prone to sampling error. Typically, longer duration studies allow more time for effects to be observed.

4. Was the study published in a peer-reviewed journal?

The peer-review process places a clinical study under the scrutiny of statisticians and scientists with expertise in the subject matter.

While the peer-review process is not perfect, it is a fairly robust and reliable way to ensure that published studies are generally well-designed and not over-interpreted. 

Typically, clinical studies without a mention of a publication denote a red flag, being absent of a critiquing process that assesses the merit of an investigation.

5. Did the clinical trial test the branded product sold to consumers?

Perhaps one of the most overlooked details of a clinical study on a supplement is whether the actual marketed product was used. Some supplements tout clinical studies conducted on similar versions of the product and not on the real ingredient or product consumers are using. The best practice is to check if the study cites the product or ingredient by brand or company name.

6. Does the use of the ingredient or product in the clinical trial match the supplement label directions?

Check to see if the dose of the product studied differs from the recommended use on your supplement label. Does it match? What about the administration of the supplement? Does the study show that the supplement was taken orally or intravenously? 

Sometimes, researchers test for a range of conditions to better understand the scope of the effects on a supplement. However, the absence of testing the recommended use leaves much to be desired within the clinical data.

7. Does the company provide access to the published study?

Copyright laws prevent companies from providing actual copies of studies to consumers. However, a link to the published journal’s website is fair-game. Many published studies are open-access, at no cost to the consumer. 

If a company does not provide any links to their published studies, it might indicate that the company is not familiar with the research, or the study was not done on the same ingredient or product you’re using. 

Explore the clinical trials behind Tru Niagen®.

Eight clinical trials fortify the ingredient, Niagen®, all of which have proven the safety and/or efficacy of Niagen®. Ten peer-reviewed manuscripts have been published with more than 30 additional ongoing clinical studies registered on www.clinicaltrials.gov. Below are the studies behind Niagen®.

1. A study published in Nature Communications in 2016 by Trammell et al.

2. A study published in PLOS One in 2017 by Airhart et al.

3. A study published in Nature Communications in 2018 by Martens et al.

4. A study published in the American Journal of Clinical Nutrition in 2018 by Dollerup et al.

5. A clinical trial published in Scientific Reports in 2019 by Conze et al.

6. A study published in the Journal of Clinical Endocrinology & Metabolism in 2019 by Dollerup et al.

7. A study published in the Journal of Physiology in 2019 by Dollerup et al.

8. A study published in Cell Reports in 2019 by Elhassan et al.

9. A study published in the American Journal of Nutrition in 2020 by Remie et al.

10. A study published in Molecular Systems Biology in 2020 by Zhang et al.

Many supplements on the market may have been tested in one or two clinical studies, but often these studies do not have the scientific rigor to meet the standards for a peer-reviewed publication.

Tru Niagen® has a global network of independent scientists eager to study its potential benefits in a wide variety of areas. 

Thus far, the clinical background shows that there is already a keen interest within the scientific community behind the ingredient, Niagen®, atypical of others. It demonstrates a level of excitement that can only further propel the research of its applicable properties. 

According to the Council of Responsible Nutrition, 77% of American adults took dietary supplements in 2019.

Dietary supplements have become a part of our daily life, filling in the gaps in our daily nutrition that our normal diet may lack. They’ve become a staple of the American kitchen counter. Grand View Research reports that the global dietary supplements market is projected to reach $230 billion by 2027. But what is a supplement? 

According to the FDA, a dietary supplement is a product that includes such ingredients as vitamins, minerals, herbs, amino acids, and enzymes. They come in forms such as tablets, capsules, soft gels, gelcaps, powders, and liquids.

Supplements are not meant to replace complete meals. As their name suggests, supplements are meant to “supplement” a healthy diet. They provide nutrients and other ingredients extracted from food sources or synthetically made.

The safety of dietary supplements.

As per FDA guidelines, supplements are not permitted to be marketed for the purpose of treating, diagnosing, preventing, or curing diseases. On the other hand, drugs are permitted for these uses if reviewed appropriately and approved by the FDA.

Ensuring the safety and efficacy of a supplement product is left to the discretion of the manufacturer. Companies like ChromaDex hold quality to high standards, ensuring their facilities meet cGMP (Current Good Manufacturing Practice) regulations.

Although the FDA does not approve dietary supplement products, any supplement that contains a new dietary ingredient (an active ingredient introduced to the market after October, 1994) must be notified to the FDA prior to market launch. 

At any time, the FDA has the power to remove a product from the market if the product is found to be unsafe.

Types of dietary supplements:

Vitamins

Vitamins are organic compounds your body needs in small quantities. 

Vitamins are essential because the human body cannot produce an adequate amount needed for sustainable function. Certain vitamins are not produced by the body at all and are solely dependent on the intake of your diet. 

For example, while your body is able to create vitamin D through the exposure of sunlight, it is unable to create vitamin C and relies solely on your food intake. 

However, the deficiencies of either vitamin can lead to serious ailments like loss of bone density or scurvy. 

There are currently 13 recognized vitamins and they are classified as either fat-soluble or water-soluble. 

Fat-soluble vitamins, like vitamins A, D, E, and K, are easily stored in the body because of their ability to be stored in the fatty tissues of the body. Your body can hold these vitamin reserves for days or weeks at a time, making good use of your food when ingested.

Water-soluble vitamins, like vitamin C and all the B vitamins, require constant intake due to their inability to be stored in the body for long periods of time. Your body quite inefficiently excretes these vitamins in urine, if not readily used. Therefore, the maintenance of these vitamins of the body requires a little more attention when considering your food choices.

For example, the vitamin B3 family, niacin, nicotinamide, and nicotinamide riboside, are all water-soluble, meaning they need daily consistent replenishment to meet your body’s required vitamin B3 intake. 

Minerals

Minerals are inorganic substances that your body requires for daily function. Minerals in your diet are essential to the body for things like bone health, muscle contraction, nerve function and controlling body fluids.

Unlike some vitamins, minerals cannot be created in the body at all. Minerals rely solely on your diet to obtain adequate amounts. The five major minerals your body requires for good health are calcium, phosphorus, potassium, sodium, and magnesium.

All other minerals are considered “trace minerals”, meaning that your body only requires a small amount of them. “Trace minerals” include iron, manganese, copper, iodine, zinc, cobalt, fluoride, and selenium.

Herbs

Herbs, also known as botanicals, have a long history for their medicinal use in ancient civilizations as far back as 5000 BCE. Traditional Chinese medicine still uses herbs as part of its practice today.

In the Western market, herbs fall within the dietary supplement category instead of standard medicine. 

As with any other supplement, herbal dietary supplements cannot claim to be a treatment for a disease or illness under the eyes of the FDA.

By definition, the term herb refers to a herbaceous plant, characterized by the lack of a woody stem and often grown low to the ground. However, there have been several exceptions to this categorization when it comes to the expansive use of herbal supplements.

Some examples of how herbal dietary supplements are used:

• Ginseng to help manage stress, support the immune system, reduce fatigue.

• Chamomile to help improve sleep quality and support relaxation.

• Cinnamon to help with appetite and blood sugar maintenance.

• Ginkgo Biloba to help support blood circulation.

Amino Acids

Amino acids are organic compounds that are vital building blocks of proteins. Your body needs 20 different kinds of amino acids for proper functioning. 

Nine of these 20 are essential amino acids because they cannot be made in the body and can only be obtained through diet. These nine essential amino acids are as follows: histidine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. 

The best sources of essential amino acids come from complete proteins like meat, dairy products, soy, and other plant-based sources, such as quinoa, buckwheat, beans, and nuts.

Amino acids are largely recognized for their role in muscle development and repair but they have several other important functions such as building antibodies, hormones and enzymes.

Enzymes

Enzymes are proteins that function as a biological catalyst, meaning that they are responsible for chemically mobilizing or accelerating chemical reactions in the body. 

Supplemental enzymes largely fall into one of two categories: digestive or systemic. 

Most people are familiar with digestive enzymes supplements that help with food digestion like lactase (used to break down milk sugar), often found in Lactaid® products. 

Systemic enzymes work in the body to help support the immune system and support inflammatory processes. One of the functions of systemic enzymes is breaking down excess fibrin, a protein involved in the clotting of blood.

Supplement categorizations are not a perfect system.

There are plenty of dietary supplement products available that don’t fit neatly into these categories, namely fatty acids or probiotics. 

Some products lie within a subsect that overlaps these categories, like metabolites. Metabolites are usually used to describe small molecules that lie within the intermediate or end product of cellular metabolism. They function as fuel, structure, signaling, or stimulatory and inhibitory effects on enzymes. 

Nicotinamide riboside is an example of a metabolite.

Supplements range in quality and proof.

The wide-range of dietary supplements on the market is overwhelming but it’s important to stay vigilant of ingredient claims, safety, and efficacy. 

Some ingredients like vitamin C have decades of scientific research to bolster their claims. However, the mass number of supplements also creates a muddled climate of varying degrees of quality and claim strength.  

Before taking in everything you read as absolute truth, it’s important to exercise an extra level of scrutiny to check for irregularities behind a supplement and the company behind it. A good place to start is reviewing the merit behind a supplement’s clinical trials.

Clinical trials are important for determining whether a supplement is safe and effective. But from where did Tru Niagen® draw its conclusions? 

Let’s take a more in-depth look into one of the key clinical studies behind Niagen® (nicotinamide riboside), the active ingredient in Tru Niagen®, to better understand its findings. 

For our examination, we’ll investigate the clinical trial published in Scientific Reports in 2019 by Conze et al.

The study design.

This particular study was conducted at KGK Science, a global contract research organization (CRO) specializing in human clinical trials for the health and nutrition industry for over 22 years. 

One hundred forty healthy and overweight adults were chosen randomly to take either one of three different daily doses (100mg, 300mg, or 1000mg) of Niagen® or a placebo for eight weeks.

The study was double-blind, meaning neither the participants nor scientists knew who received Niagen® and who received the placebo until the study was done. These parameters are essential to assure the objectivity of the clinical results.

The safety and effects of Niagen® were measured by monitoring NAD+ metabolite concentrations in urine and blood. Subjects were instructed to avoid foods that contained high amounts of tryptophan and vitamin B3, both nutrients that can elevate NAD+ levels.

Subjects consumed their assigned study product for 56 days, attending the clinic for blood and urine tests on Day 7, 14, 28, and 56.

The study results.

Subjects who consumed 100, 300, and 1000mg of Niagen® showed a dose-dependent increase in whole-blood NAD+ and other NAD+ metabolites within two weeks. The results are as follows:

The increases remained elevated throughout the remainder of the study, and no reports of flushing of the skin (a common side effect of Niacin, another vitamin B3) were observed. 

Although participants in all groups, including the placebo, reported some unwanted side effects, none of these were serious or attributable to Niagen®. It’s common and even expected for people in a clinical trial to report some adverse events. This is one of the reasons the placebo group is so important.

Why do we recommend 300mg?

Our recommendation of 300mg per day is rooted in this study. Results show those particular subjects who took 300mg a day experienced an average increase of 40-50% in whole-blood NAD+ in as little as two weeks. The graph below shows the level of whole-blood NAD+ for 300mg at different intervals (the day the subjects checked in at the clinic). Importantly, NAD+ levels remained elevated throughout the rest of the study compared to the placebo group.

The importance of daily supplementation.

Niagen® is a novel form of vitamin B3, but still holds the water-soluble properties of other vitamin B3s. Water-soluble vitamins require constant intake due to their inability to be stored in the body for long periods. Your body excretes these vitamins in urine, if not readily used. 

Our recommendations are based on science.

Taking the right serving size of Tru Niagen® every day is not just a frivolous suggestion. As careful advisors to your cellular health, we continuously strive to make our recommendations rooted in research and scientific expertise. With ten clinical trials and counting, we continue to build upon our research, shaping Tru Niagen® to be an important staple for your supplement routine.