Nicotinamide adenine dinucleotide (NAD+) is a cofactor and coenzyme found in our cells that plays an essential role in cellular function, mitochondrial health, and energy production. Also, NAD+ is an important cofactor in the reactions that repair DNA damage and modify gene expression on a cellular level. As we age, our levels of NAD+ naturally decline and this decline can be associated with a higher risk of diseases, cognitive dysfunction, and dysregulated immune system responses. Recently, there has been a growing interest in NAD+ and it’s range of biological activities for mental clarity, fatigue, anti-aging, recovery, neuroprotection, and more. 

What is NAD+?

In our cells, NAD+ has a variety of functions that make it a crucial supporter of both cellular and overall health. 

NAD+ functions 

  • Energy and antioxidation: NAD+ is crucial for oxidation-reduction reactions and neutralizing free radicals. It moves electrons in cellular reactions in the mitochandrial electron transport chain, which is what makes ATP (cellular energy). 
  • Cellular and DNA repair: NAD+ acts as a cofactor for PARPs, which are a group of enzymes that repair DNA. It is also used by sirtuins, which are proteins that alter gene expression and promote longevity. 
  • Metabolic Pathways: NAD+ is an essential cofactor for the reactions that enable cells to process the carbohydrates, fats, and proteins that we eat into energy that the cells can use (mainly ATP). 

NAD+ is derived from vitamin B3 and is made and recycled naturally by our cells. But there are a variety of circumstances that can cause lower NAD+ levels: 

 

Benefits of NAD+ IV/IM Therapy

Fatigue 

NAD+ aids in the proper functioning of mitochondria to produce ATP and support optimal energy levels in the brain and body. Lower levels of NAD+ (from aging, chronic inflammation, metabolic diseases, etc.) can contribute to lower energy levels and fatigue. In myalgic encephalomyelitis/chronic fatigue syndrome, supplementing NAD+, along with CoQ10 (another antioxidant), was found to decrease both general fatigue and cognitive fatigue (aka brain fog). 

Brain Health 

Preclinical trials suggest that NAD+ could be effective for various forms of dementia. NAD+ may help protect neurons from inflammation and oxidative stress that can cause damage implicated in neurodegeneration. This neuroprotection can be linked to the NAD+ dependent sirtuins (mainly SIRT1), which has been found to be protective against acute and chronic neurological diseases. SIRT1 has anti-inflammatory actions and plays roles in DNA integrity, cognitive function and memory, brain integrity, and neuroplasticity. 

Aging 

NAD+ plays a role in many of the processes related to aging, including DNA stability, clearing damaged proteins, inflammation, mitochondrial dysfunction and more. It has been found that increasing NAD+ precursors can aid in correcting loss of physical performance, decreasing blood pressure, and helping improve fatigue in older adults. NAD+ decline is observed in various tissues, including cardiac tissue, which is found to be affected by aging, obesity, and hypertension. This is a target of NAD+ therapy and ongoing research. 

Burnout, Stress, and Mood 

Neuroinflammation has been found to be a component of both burnout/chronic stress and mood disorders like depression. Managing this inflammation can help to improve depression and other symptoms, such as fatigue and brain fog. Early studies are being done on NAD+-dependent modulator proteins (SIRT1, SIRT2) for their potential to work as anti-depressants through the targeting inflammation. 

Fertility

Sirtuins (mainly SIRT1 and SIRT3) protect against oxidative stress in the gametes and are crucial for oocyte quality and reproductive aging. Declining NAD+ levels with age contribute to ovarian aging and reduced oocyte quality, which negatively impacts fertility. Animal studies have shown that NAD+ precursors can improve oocyte quality, fertility outcomes, and slow ovarian aging, while early human research suggests similar potential. This work highlights a promising, non-invasive therapeutic approach to enhance fertility in women of advanced maternal age, either through oral supplementation or as an adjunct in IVF. As more research in this area comes out the exact roles, mechanisms, and most effective ways to raise ovarian NAD+ levels will hopefully be discovered. 

Exercise and Recovery 

During exercise, cellular metabolic processes accelerate to meet the energy demands of the muscle cells, which requires rapid cycling of NAD+ in the mitochondria. NAD+ also supports proper mitochondria functioning and antioxidant/anti-inflammatory efforts, which are both important for proper recovery from exercise. 

Addiction

Lower levels of NAD+ in the brain has been found to be a part of the neurobiology of addiction. NAD+ therapy has been found to be effective in reducing cravings and withdrawal symptoms in the treatment of substance use disorders and addiction. 

 

NAD+ IV/IM Therapy

NAD+ therapy is a safe and effective way to support a variety of health goals. There has been lots of research done on using NAD+ precursors to raise NAD+ levels; one of the most effective way is through IV/IM NAD+. Doing IV/IM therapy delivers NAD+ directly to your bloodstream, bypassing the GI system and potentially leading to higher bioavailability than oral supplements especially if there is problems with absorption in the gut. NAD+ IM injections tend to be better tolerated than the IV treatments, but can have lower absorption and IV’s are recommended for more complex chronic cases/conditons. IM injections of NAD+ are also faster (IV’s usually need to be dripped slowly over multiple hours) and can also be less costly. 

The most common side effects with NAD+ therapy are: 

  • Nausea
  • Anxiety-like effects
  • Muscle tension 
  • GI effects
  • Headaches 

The side effects are mild and tend to stop as soon as the infusion is completed. As NAD+ is a relatively new therapy, there is not much research done on long-term effects, but short-term NAD+ therapy appears to be well-tolerated. It’s important to discuss NAD+ therapy with a medical professional who can help create a personalized plan and approach based on your specific medical needs, medical conditions, and goals. 

Dr. Tia Patychuk ND