Increase Antioxidants to Improve Fertility – A Novel Approach via Nrf2

A lot of attention is given to taking antioxidants like CoQ10, Vitamin C, and others to improve fertility.  However, there may be a more effective way to increase antioxidant levels...by stimulating your body's own antioxidant production.

Why are antioxidants so important to preserving egg quality and fertility as you age?  Because they shield your eggs' (and sperm's) DNA from damage by oxidants.

Less known though is that a certain amount of oxidative stress is needed for the reproductive processes to work properly.

At the heart of the body’s antioxidant defense system lies the Nrf2 pathway.  Nuclear factor erythroid 2-related factor 2 (Nrf2) is your body’s master regulator of antioxidant defense.

Nrf2 controls the production of over 200 proteins that protect your cells from oxidative stress.

How does this work? Too much ROS (reactive oxygen species) in the cell prompts Nrf2 to move into the cell nucleus. There, it activates the production of your body’s antioxidant enzymes. (study)

Too little Nrf2 activity causes an imbalance in the cell, leading to oxidative stress.  Studies show that low Nrf2 can cause chronic diseases such as type 2 diabetes and heart disease. (study)(study)

What is oxidative stress?

Let’s back up a minute and dive into what is going on with ROS...

Inside your cells, a balance the transfer of electrons between molecules is essential.

An imbalance between pro-oxidants (ROS) and antioxidants in the cell leads to oxidative stress. This happens when ROS production is greater than the antioxidant system can handle.

What exactly is ROS? ROS is a general term for reactive molecules such as hydrogen peroxide and superoxide. (source)

Your mitochondria naturally produce ROS as a byproduct of energy production. Your cells can also produce ROS when breaking down toxins. Thus, too many toxins can lead to oxidative stress in the cells.

ROS, in the right amounts though, can act as a signaling molecule in the cell. So the goal is to keep it in balance, rather than to eliminate it completely.

Too much can cause damage, but some ROS is necessary. (study)

How does Nrf2 affect fertility?

As the follicle cell develops into the egg cell ready for ovulation, ROS plays an important role. While too much ROS damages the egg cell, there are periods during egg cell development when ROS acts as a signaling molecule.

Oxidative stress is tightly regulated in the ovaries. As the follicle cell begins to develop into the mature egg cell, a lot of energy is needed from the mitochondria. This, in turn, produces a high level of ROS. The ROS then causes activation of the body’s antioxidant system through the Nrf2 pathway. (study)(study)

NRF2

Studies show that too much oxidative stress plays a role in infertility in women (and men). Our modern world is full of stress and environmental toxin exposure. Thus, the balance is almost always tipped towards too much ROS instead of too much on the antioxidant side. (study)(study)

The key is to activate the Nrf2 signaling pathway so that your body naturally balances out the excess oxidative stress.

What happens without enough Nrf2? Animal studies show that stopping the Nrf2 signal will stop the development of an egg cell prior to ovulation. We definitely don’t want that! (study)

Other studies show that activating the Nrf2 pathway delays age-associated fertility problems! (study)

A number of other studies show the importance of balancing oxidative stress and activating the Nrf2 pathway. This is true for the development of the egg cell and also for the growing baby. (study)

How to increase Nrf2?

Several ways can safely increase Nrf2 when trying to conceive.

First, regular exercise increases ROS which then also increases Nrf2. The key here is ‘regular exercise’.

A sudden spurt of hard exercise will increase Nrf2 in response to the ROS produced in the mitochondria. But you don’t just want a short increase in Nrf2 in the muscles.

Instead, moderate exercise that is done regularly upregulates Nrf2 throughout the body in anticipation of more exercise tomorrow.  (study) (study)

Next, there are natural plant polyphenols that can increase Nrf2.

  • Curcumin, found in the spice turmeric, increases the Nrf2 signal and decrease oxidative stress in the egg cell. (study) You can take curcumin as a supplement (best absorbed with piperine included), or you can liberally use turmeric in your cooking.
  • Citrus fruits contain naringenin, which has also been shown to increase Nrf2 levels. An animal study showed that this is effective both in the uterus and for endometriosis. (study)
  • Broccoli is a rich source of sulforaphane, which is a potent activator of Nrf2. (study) Broccoli sprouts have the highest amounts of sulforaphane and are great to use in a smoothie or to take as a supplement.
  • A diet rich in olive oil increases Nrf2. The polyphenols in olive oil decrease oxidative stress in the cells. (study)

3 Steps you can take today to boost Nrf2:

  1. Making time to exercise regularly is important for fertility in many ways. Create a routine of getting moderate exercise every day.  This can be as simple as changing where you park so that you get in a 15-minute brisk walk to and from work. Or you could get some weights and resistance bands to use for a half hour each evening while watching Netflix.
  2. If your diet isn’t abundant in polyphenol-rich foods, you may want to consider supplementing. Try adding in curcumin, sulforaphane, or naringenin.  While you don’t want to go overboard with high doses of antioxidant supplements, most people will benefit from adding in antioxidants.
  3. Even if you choose to supplement, adding in foods such as broccoli and olive oil are easy ways to boost your Nrf2 and balance out your diet. Focus on getting fresh vegetables in your diet each day, and choose organic whenever possible.