What is Protandim and does it really work?

Answer:

Protandim (from LifeVantage) is promoted to reduce oxidative stress (cellular damage that can result in cellular dysfunction and death) by stimulating the body's own production of antioxidants. Oxidative stress is associated with diseases such as cardiovascular disease, Alzheimer's disease, multiple sclerosis (MS), Parkinson's disease and cancer, and is also thought to play a major role in aging, as the body becomes less efficient as repairing cellular damage.

What's in Protandim
One Protandim caplet contains 675 mg of a patented proprietary blend. Although the label does not list amounts of the ingredients in the blend, the following amounts are listed in the in the patent: milk thistle extract (225 mg - 80% silymarin), Bacopa extract (150 mg - 45% bacosides), Ashwagandha root powder (150 mg), green tea extract (75 mg - 98% polyphenols) and turmeric extract (75 mg -95% curcumin). A daily serving of one caplet provides, with the exception of milk thistle extract, amounts of each ingredient far below those used in clinical trials. According to researchers who conducted a clinical study on Protandim, each of these ingredients has been reported to increase levels of antioxidant activity in the body, but a low dose of each was chosen to avoid unwanted pharmacological effects (Nelson, Free Radic Biol Med 2006). Protandim also contains a tiny amount of caffeine (1.8 mg) per caplet, likely from its green tea extract.

Nrf2 and use in multiple sclerosis (MS)
While there are a number of studies on Protandim that have created a lot of press and "marketing buzz," the majority of these are in-vitro and animal studies. Among these preliminary studies, one found that, in cultured cells, Protandim activated Nrf2, a protein that stimulates genes that respond to free radicals and oxidative stress, and another found it to improve markers of oxidative stress in mice (Reuland, Free Radic Biol Med 2013; McClure J Diet Suppl 2010). However, it is not clear at this time whether Protandim has the same effect in people, or whether these potential effects are beneficial. Protandim is popular among people with MS, partly because it activates Nrf2, which is also an effect of Tecfidera, a prescription medication for MS. However, the exact way that Tecfidera works for MS is unknown and may not be related to its ability to activate Nrf2 (Prescribing Information for Tecfidera, Revised 1/2021). Furthermore, there are no clinical trials confirming the benefit of Protandim in people with MS.

Limited clinical studies
There are just two small studies of Protandim supplementation in humans. The first is the basis for LifeVantage's claim on its website that Protandim is "the only supplement clinically proven to reduce oxidative stress in humans by an average of 40 percent in 30 days." In the study, which was not double-blind nor placebo-controlled, 29 healthy men and women took one caplet of Protandim (675 mg of its proprietary blend) daily for 4 months (Nelson, Free Radic Biol Med 2006). After 30 days of supplementation, there was a 40% decline in TBARS (a measure of free radical breakdown of fat), and a 30% increase in levels of the antioxidant superoxidant dismutase (SOD) in red blood cells. Levels of CRP, a measure of inflammation in the body and a marker of cardiovascular health, were not reduced, nor were cholesterol levels. Whether or not the changes would result in any specific health benefit was not determined.

The second clinical study on Protandim was double-blinded, randomized and placebo-controlled, making the results more reliable, although it was quite brief — just 7 days.  The study compared the effects of a much larger dose (1,350 mg/day) of Protandim with a placebo on TBAR levels and measures of lung health in 30 otherwise healthy people with alcohol use disorders (Burnham, Am J Physiol Lung Cell Mol Physiol 2012) . Protandim was not found to significantly lower TBAR levels or improve measures of lung health compared to placebo. Interestingly, this study is not mentioned on LifeVantage's website.

Safety and side effects
There were no safety concerns raised by these two clinical studies; however, in the first study, there was a non-significant rise in uric acid levels reported. People who have gout or other conditions affected by uric acid levels may want to take this into consideration. Milk thistle and other herbs in this supplement may cause allergic reactions in some people, or may interact with certain medications (See the Cautions and Concerns section of the Milk Thistle, Green Tea and Turmeric Reviews for more information).

Be aware that there are some concerns about taking antioxidant supplements under certain conditions. For example, high doses of resveratrol, vitamin C and E may reduce some of the benefits of exercise and high doses of vitamin E may increase the risk of death from prostate cancer. Also, be aware that the American Cancer Society advises that cancer patients undergoing treatment avoid taking high doses of antioxidant supplements (American Cancer Society 2013).

In 2012, certain lots of Protandim were recalled due to the risk of containing metal fragments.

Cost
A 30-day supply of Protandim (one 675 mg caplet/day) costs about $50 and can be purchased directly through LifeVantage, or through other major retailers. (The company also makes a pet product, LifeVantage Canine Health, which includes the same ingredients as Protandim.)
 

The bottom line: Does Protandim really work?

Protandim may have antioxidant activity, but there is little evidence that it provides any therapeutic benefit in humans.