Coenzyme Q10 (CoQ10) has been available in supplemental form for more than 40 years. The availability of supplemental NAD+ (nicotinamide adenine dinucleotide) boosters is a more recent development. NAD+ is derived from the B vitamin niacin. In this article, we explain the interaction between CoQ10 and NAD+. You may want to take both CoQ10 and NAD+ booster supplements to reduce feelings of fatigue.
What Are Coenzyme Q10 and NAD+?
Middle-aged and elderly individuals may lack energy. Combined supplementation with CoQ10 and NAD+ boosters may reduce fatigue levels.
Both CoQ10 and NAD+ are substances that have a vital role in the biochemical processes within mitochondria. These processes help the mitochondria supply all cells with the energy they require to maintain normal functioning. They may help enhance energy levels and reduce fatigue levels.
CoQ10 and NAD+ also function (although by different mechanisms) as antioxidants, protecting cells from free radical induced oxidative stress. CoQ10 exists in two molecular forms, oxidized (ubiquinone) and reduced (ubiquinol). The normal function of CoQ10 involves the continual interconversion (approximately 5000 times per hour) of these two CoQ10 forms.
Just as CoQ10 exists in two molecular forms, there are two forms of NAD, oxidized (NAD+) and reduced (NADH). As with CoQ10, the normal functioning of NAD involves the continual interconversion of these two forms.
How Do CoQ10 and NAD+/NADH Work Together?
CoQ10 and NAD+ are critical components of the electron transport chain (ETC) within mitochondria. The ETC makes possible the generation of cellular energy in the form of ATP. Ubiquinone/ubiquinol and NAD+/NADH act together as a redox couple within Complex 1 of the ETC.
In the processes involved in breaking down food to energy, NAD⁺ accepts electrons, and is reduced to NADH. NADH then provides electrons at the start of the transport chain. CoQ10 is responsible for the transfer of those electrons farther within the chain. Together, in adequate supply, NAD+ and CoQ10 can enhance the efficiency of ATP energy synthesis. In so doing, they can also lower the extent of harmful free radical generation – a by-product of ATP production [Mantle 2024].
Why Do Middle-aged and Older Adults Need CoQ10 and NAD+?
Supplementation with CoQ10 and NAD+ seems to be especially important for middle-aged and older adults. Often, they experience age-related declines in the synthesis of both substances. Furthermore, they are at an age in which the extent of mitochondrial dysfunction, oxidative stress, and chronic low-grade inflammation increases.
Age-related low NAD+ status limits the supply of electrons to the electron transfer chain. NAD+ booster supplementation is often needed to restore the flow of electrons that results in the generation of ATP energy. Age-related decline in the body’s synthesis of CoQ10 can result in less-than-optimal ATP energy generation.
How Does One Boost NAD+ Synthesis?
Generally, the uptake of NAD+ and NADH from oral supplements into the blood does not benefit the cells and tissues very much [Rajman 2018]. It is better for the cells themselves to synthesize the NAD+ (and the NADH via redox reactions).
Consequently, it is more effective to take a niacin supplement as an NAD+ booster [Pirinen 2020]. Rather than acquire NAD+ and/or NADH directly from supplements, the body should produce NAD+ (and NADH) using the vitamin B3 precursors as building blocks [Rajman 2018].
Is NAD+ a Substrate of the Sirtuins?
In addition to its role in bio-energetics, NAD+ is important as a co-substrate of the sirtuins. The sirtuins are a family of signaling proteins involved in metabolic regulation [Houtkooper 2012].
Low levels of sirtuins are associated with impaired mitochondrial function, decreased ATP production efficiency, and increased oxidative stress [Wu 2014].
In the KiSel-10 randomized controlled trial enrolling elderly Swedish adults, Alehagen et al reported that combined CoQ10 and selenium supplementation was associated with significantly increased serum concentrations of SIRT1. In the placebo group, the SIRT1 levels decreased over the same period [Opstad 2023].
What Do Clinical Studies of CoQ10 and NADH Supplementation Show?
In Spain, the research team around Jesus Castro-Marrero has conducted three randomized controlled trials of combined CoQ10 and NAD+ booster supplementation in patients with chronic fatigue syndrome. In all three trials, the researchers administered CoQ10 200 mg/day and NADH 20 mg/day. In all of the studies, the researchers observed less fatigue and better quality of life in the active treatment group [Castro-Marrero 2015, 2016, 2021]:
- 2021: 207 patients for 12 weeks
- 2016: 80 patients for 8 weeks
- 2015: 73 patients for 8 weeks
Combined CoQ10 and NADH Study Findings
For example, in 2015, Castro-Marrero et al reported the following significant outcomes of the active treatment compared with the placebo treatment:
- higher levels of CoQ10 and NADH
- lower levels of NAD+/NADH ratio
- lower levels of fatigue
- lower levels of lipoperoxides
- higher levels of ATP
Note that the researchers measured CoQ10, NADH, and ATP levels in peripheral blood mononuclear cells (PBMCs). The reason the researchers chose to do the measurements in PBMCs and not in plasma is simple. PBMCs are living immune cells (lymphocytes, monocytes) that contain mitochondria and show active mitochondrial function, e.g., ATP synthesis. Plasma does not contain mitochondria and cannot show changes in cellular energy metabolism.
Combined CoQ10 and NADH Supplementation and ATP Levels
This 2015 Castro-Marrero study is especially important because it shows combined CoQ10 and NADH supplementation associated with increased ATP levels.
Unfortunately, the above-summarized Castro-Marrero studies are the only reported clinical trials of combined CoQ10 and NADH supplementation. More clinical trials are warranted, not only in chronic fatigue syndrome patients but also in healthy elderly adults, in cardiovascular disease patients, and in study participants engaging in strenuous exercise.
Need for More Studies of Combined CoQ10 and NAD+ Booster Supplementation
Note: It is somewhat unusual to supplement directly with NADH rather than with a NAD+ booster such as niacin or nicotinamide riboside. Castro-Marrero et al used a compound that was the reduced form of nicotinamide adenine dinucleotide. Being the reduced form of the NAD⁺ molecule, the NADH carried electrons that it could later donate. The NADH preparation was enteric-coated to protect the NADH from acid degradation in the stomach and to improve its delivery to the small intestine.
NADH is chemically unstable in acidic environments. Taken orally without the enteric coating, the NADH would not have been bioavailable.
There are, to date, no studies comparing combined CoQ10 and NADH supplementation with combined CoQ10 and NAD+ booster supplementation, e.g., CoQ10 plus niacin or CoQ10 plus nicotinamide riboside.
Conclusion: Combined CoQ10 and NAD+ Booster Supplementation?
Logically, there should be health benefits from combined CoQ10 and NAD+ Booster supplementation in middle-aged and elderly adults.
- improved mitochondrial energy production
- reduced oxidative stress
For the potential consumer of combined CoQ10 and NAD+ Booster supplements, the following questions are germane:
- Is there solid documentation for the absorption and bioavailability of the CoQ10 supplement?
- Is it more efficient to take an NAD+ booster supplement, e.g., niacin or nicotinamide riboside, or to take NADH directly?
Sources
Castro-Marrero J et al. Effect of dietary Coenzyme Q10 plus NADH supplementation on fatigue perception and health-related quality of life in individuals with myalgic encephalomyelitis/chronic fatigue syndrome: a prospective, randomized, double-blind, placebo-controlled trial. Nutrients. 2021 Jul 30;13(8):2658.
Castro-Marrero J et al. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome. Clin Nutr. 2016;35:826-34.
Castro-Marrero J et al. Does oral Coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?
J Antioxidants & Redox Signaling. 2015;679-685.
Houtkooper RH et al. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012 Mar 7;13(4):225-238.
Mantle D, Dewsbury M, Hargreaves IP. The Ubiquinone-ubiquinol redox cycle and its clinical consequences: an overview. Int J Mol Sci. 2024 Jun 20;25(12):6765.
Opstad TB et al. Increased SIRT1 concentration following four years of selenium and Q10 intervention associated with reduced cardiovascular mortality at 10 year follow up—sub study of a previous prospective double blind placebo controlled randomized clinical trial. Antioxidants (Basel). 2023;12(3):759.
Pirinen E et al. Niacin cures systemic NAD+ deficiency and improves muscle performance in adult-onset mitochondrial myopathy. Cell Metabolism. 2020;31:1078-1090.
Rajman et al. Therapeutic potential of NAD-boosting molecules: the in-vivo evidence. Cell Metab. 2018;27(3):529–547.
Wu YT et al. Roles of sirtuins in the regulation of antioxidant defense and bioenergetic function of mitochondria under oxidative stress. Free Radic Res. 2014 Sep;48(9):1070-84.
The information presented in this review article is not intended as medical advice. It should not be used as such.
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