What is NAD? Do NAD supplements work?

Driven by emerging research, the interest in NAD supplements and their potential benefits in enhancing cellular health and combating ageing is growing rapidly. Let’s take a look at what the hype is all about.

What is NAD?

Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells. It plays a crucial role in cellular metabolism and energy production.

As NAD+ levels naturally decline with age,1 scientists and people looking to improve their health and wellbeing are exploring supplements like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) to boost NAD+ levels in the body.

• Electron Acceptor: NAD+ functions as an oxidising agent in metabolic reactions, accepting electrons from other molecules. This role is crucial in catabolic reactions, which break down molecules to release energy.
• Redox Reactions: In cellular respiration, NAD+ is reduced to NADH in glycolysis and the citric acid cycle (Krebs cycle).
• Sirtuins and DNA Repair: NAD+ is a substrate for sirtuins, a family of proteins involved in regulating cellular processes such as ageing, transcription, and apoptosis. It is also used by enzymes involved in DNA repair.
• Cell Signalling: NAD+ is involved in cell signalling and can influence various biological processes, including ageing and stress responses.

NADH is the reduced form of NAD+, with the addition of a pair of electrons and a hydrogen ion (H+). NADH functions as a reducing agent, donating electrons to other molecules. This role is crucial in anabolic reactions, which build up molecules and store

NAD’s Impact on Aging and Longevity

NAD plays a crucial role in ageing and longevity due to its involvement in various cellular processes that maintain cellular health and function 6. Let’s take a look at its impacts.

1. Mitochondrial Function and Energy Production

NAD+ is essential for mitochondrial function and energy production through its role in the electron transport chain (ETC) and oxidative phosphorylation. As we age, NAD+ levels decline, leading to reduced mitochondrial function and energy production. This decline contributes to cellular fatigue, decreased metabolism, and the development of age-related diseases.

Maintaining NAD+ levels helps sustain mitochondrial function, improving cellular energy and potentially extending lifespan.

2. DNA Repair and Genomic Stability

NAD+ is a substrate for poly(ADP-ribose) polymerases (PARPs) and sirtuins, enzymes involved in DNA repair and maintenance. Reduced NAD+ levels impair the activity of these enzymes, leading to accumulation of DNA damage, genomic instability, and increased risk of age-related diseases.

Enhancing NAD+ levels supports efficient DNA repair, preserving genomic stability and promoting healthy ageing.

4. Cellular Senescence

NAD+ influences cellular senescence, a state of irreversible cell cycle arrest associated with ageing. Lower NAD+ levels contribute to the accumulation of senescent cells, which secrete pro-inflammatory factors and damage surrounding tissues.

Maintaining NAD+ levels can reduce the burden of senescent cells, promoting tissue health and longevity 7.

5. Metabolic Regulation

NAD+ is involved in various metabolic pathways, including glycolysis, the citric acid cycle, and fatty acid oxidation. Metabolic dysfunction is a hallmark of ageing. Declining NAD+ levels disrupt these metabolic processes, leading to metabolic disorders such as obesity, diabetes, and cardiovascular diseases.

Supporting NAD+ levels can improve metabolic health, reduce the risk of metabolic diseases, and promote a longer, healthier life 8.

6. Inflammation and Immune Function

NAD+ modulates immune responses and inflammation through its role in cellular signalling and metabolism. Chronic inflammation, often termed "inflammaging," is associated with ageing and age-related diseases. Lower NAD+ levels can exacerbate inflammatory responses.

Increasing NAD+ levels can modulate inflammation and improve immune function, potentially reducing the risk of age-related inflammatory diseases 8. 

NAD+ is integral to various cellular processes that are crucial for maintaining health and function as we age. By supporting mitochondrial function, DNA repair, sirtuin activation, metabolic regulation, and inflammation control, NAD+ plays a significant role in promoting longevity and reducing the impact of age-related diseases.

How NAD Functions in the Body: An In-Depth Overview

NAD functions as a crucial coenzyme in the body, facilitating a wide range of biochemical reactions essential for cellular metabolism and overall health. This includes cellular metabolism, energy production, DNA repair, and ageing.

Role in Cellular Metabolism and Energy Production

(NAD) plays a critical role in cellular metabolism,2 particularly in redox reactions that are essential for energy production and various metabolic processes.3

Here’s an overview of its key functions:

Glycolysis

In glycolysis, NAD+ accepts electrons during the conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, forming NADH. This step is crucial for the continuation of glycolysis, allowing the cell to produce ATP anaerobically.

Citric Acid Cycle (Krebs Cycle)

NAD+ is reduced to NADH in several steps, including the conversion of isocitrate to alpha-ketoglutarate, alpha-ketoglutarate to succinyl-CoA, and malate to oxaloacetate. These reactions are vital for the complete oxidation of acetyl-CoA, generating electron carriers for the electron transport chain.

Electron Transport Chain (ETC)

NADH donates electrons to Complex I of the electron transport chain, initiating a series of redox reactions that ultimately lead to the production of ATP. The transfer of electrons through the ETC creates a proton gradient across the inner mitochondrial membrane, driving the synthesis of ATP via oxidative phosphorylation.

Fermentation

In the absence of oxygen, cells regenerate NAD+ from NADH to allow glycolysis to continue. For example, in lactic acid fermentation, pyruvate is reduced to lactate by NADH, regenerating NAD+. This regeneration is essential for anaerobic energy production, enabling cells to survive in low-oxygen conditions.

Fatty Acid Oxidation

NAD+ is involved in the beta-oxidation of fatty acids, where it is reduced to NADH during the dehydrogenation steps. This process is crucial for converting fatty acids into acetyl-CoA, which enters the citric acid cycle for further ATP production.

Amino Acid Metabolism

NAD+ participates in the deamination of amino acids and other catabolic pathways, assisting in the breakdown and utilisation of amino acids. These reactions are vital for the maintenance of nitrogen balance and energy production from amino acid catabolism.

In summary, NAD is indispensable in cellular metabolism, acting as a key electron carrier in various metabolic pathways. Its roles in glycolysis, the citric acid cycle, the electron transport chain, and other metabolic processes are fundamental for energy production and overall cellular function.

Importance in DNA Repair and Maintenance

NAD plays a significant role in DNA repair and maintenance, which is critical for preserving genomic stability and preventing disease.

Here’s how it works:

1. Substrate for Poly(ADP-ribose) Polymerases (PARPs)

PARPs are a family of enzymes that detect and signal DNA damage.When DNA strand breaks occur, PARP enzymes use NAD+ as a substrate to add ADP-ribose polymers to target proteins, including themselves. This process is called poly(ADP-ribosyl)ation.

Poly(ADP-ribosyl)ation modifies chromatin structure and recruits DNA repair proteins to the site of damage, facilitating the repair process.

2. Involvement in Base Excision Repair (BER)

BER is a cellular mechanism that repairs damaged DNA bases. PARP1, a key enzyme in BER, binds to single-strand breaks and uses NAD+ to add ADP-ribose units, signalling the presence of damage and attracting repair enzymes such as DNA ligase III and DNA polymerase β.

This pathway is essential for fixing small, non-helix-distorting base lesions, maintaining the integrity of the DNA.

3. Role in Sirtuins Activity

Sirtuins are a family of NAD+-dependent deacetylase enzymes involved in DNA repair, gene expression, and metabolism. Sirtuins, particularly SIRT1 and SIRT6, use NAD+ to deacetylate proteins, including histones and other proteins involved in DNA repair 4.

Deacetylation by sirtuins influences chromatin remodelling and the activation of DNA repair pathways, such as non-homologous end joining (NHEJ) and homologous recombination (HR).

4. Regulation of Cellular Stress Responses

NAD+ levels modulate cellular responses to stress and damage. High levels of NAD+ enhance the activity of PARPs and sirtuins, promoting efficient DNA repair and stress resistance 5. Conversely, low NAD+ levels can impair these processes, leading to accumulation of DNA damage.

Efficient DNA repair and stress response mechanisms are crucial for preventing the onset of age-related diseases and maintaining cellular health.

NAD+ is vital for DNA repair and maintenance through its role as a substrate for key enzymes like PARPs and sirtuins. These enzymes are crucial for detecting DNA damage, signalling repair mechanisms, and modulating the chromatin environment to facilitate repair.

Understanding NAD Supplements

NAD supplements on the market primarily include precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which are designed to boost NAD+ levels, and are available in various forms such as capsules, powders, and tablets.

Common Forms of NAD Supplements

Nicotinamide Riboside (NR)

Nicotinamide Riboside (NR) is a form of vitamin B3 and a precursor to NAD+, which is essential for various cellular processes. NR is naturally found in trace amounts in some foods, such as milk, and is used in supplements to boost NAD+ levels in the body.

Nicotinamide Mononucleotide (NMN)

Nicotinamide Mononucleotide (NMN) is a nucleotide derived from vitamin B3 (niacin) and serves as a direct precursor to NAD+. NMN is found naturally in small amounts in foods like broccoli, avocado, and cabbage, and is used in supplements to increase NAD+ levels in the body.

How NAD Supplements Aim to Boost NAD Levels

NAD supplements aim to boost NAD levels by providing the body with precursors that are readily converted into NAD+. Once ingested, NR and NMN are metabolised into NAD+ through a series of enzymatic reactions within the cells.

By increasing the availability of these precursors, NAD supplements can enhance the body's ability to produce NAD+ – supporting various cellular processes that rely on this crucial coenzyme.

Potential Side Effects of NAD Supplements

Common side effects of NAD supplementation might include:

• Nausea: Some individuals may experience stomach discomfort or nausea, particularly when starting supplementation.
• Fatigue: Some users report feeling tired or fatigued initially.
• Headaches: Mild to moderate headaches can occur as the body adjusts to increased NAD+ levels.
• Digestive Issues: Diarrhoea, bloating, or other gastrointestinal issues might be experienced.
• Flushing: Similar to other vitamin B3 derivatives, NAD+ precursors can cause skin flushing in some individuals.

It is important to speak with a doctor before starting NAD supplements, especially if you have any pre-existing conditions or are taking other medications.

Who Should Avoid NAD Supplements?

• Pregnant or Breastfeeding Women: There is limited research on the safety of NAD supplements during pregnancy and lactation.
• People with Certain Medical Conditions: Those with liver disorders, kidney issues, or cancer should avoid NAD supplements unless advised otherwise
• Individuals on Specific Medications: NAD supplements may interact with medications, particularly those affecting the liver or those with known interactions with vitamin B3 derivatives.

Recommendations for Safe Usage

• Speak with a doctor before starting NAD supplements, especially if you have pre-existing medical conditions, are pregnant, breastfeeding, or are taking other medications.
• Start with low doses to assess your body's response and gradually increase if needed.
• Follow manufacturer instructions – adhering to dosage and usage guidelines provided on the product you’re using.
• Monitor for side effects and discontinue use if severe adverse reactions occur.
• Schedule regular check-ups with your doctor to monitor your health and adjust the dosage if necessary.
• Avoid long-term use without supervision to avoid potential risks associated with prolonged supplementation.

Do NAD+ levels supplement work?

The effectiveness of NAD+ level supplements, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), has been a subject of considerable research and interest. Studies in animals have shown promising results, indicating that these supplements can enhance mitochondrial function, improve metabolic health, and potentially extend lifespan. Some human studies also suggest benefits, including improved muscle function, better cognitive performance, and increased markers of cellular repair and metabolism.

However, the research is still in its early stages, and long-term effects and safety in humans are not fully understood. While initial findings are encouraging, more extensive clinical trials are needed to confirm the efficacy and safety of NAD+ supplements. Additionally, individual responses can vary, and the optimal dosage has yet to be established.

Looking to increase your health and longevity? We’ve created a longevity range packed with supplements aimed at reducing the risk of age-related diseases, promoting vitality, and enhancing overall well-being for a prolonged, healthier life.

6 Natural Methods to Increase NAD

There are several natural methods to increase NAD+ levels in the body:

• Dietary Sources: Eat foods rich in NAD+ precursors like tryptophan and niacin (vitamin B3). Foods include:
  
  - Fish
  - poultry
  - lean meats
  - Whole grains
  - Green vegetables, such as broccoli and kale
  - Dairy products
• Exercise: Regular physical activity, particularly aerobic exercises like running, cycling, and swimming, can boost NAD+ levels by stimulating NAD+ biosynthesis and enhancing mitochondrial function.
• Intermittent Fasting and Caloric Restriction: These practices can increase NAD+ levels by promoting mitochondrial biogenesis and activating sirtuins, which are NAD+-dependent enzymes.
• Healthy Sleep Patterns: Ensure adequate and quality sleep, as NAD+ levels are linked to circadian rhythms and proper sleep can support its production.
• Sunlight Exposure: Moderate exposure to sunlight can help increase NAD+ levels, as vitamin D synthesis and circadian rhythm regulation are influenced by sunlight.
• Avoid Excessive Alcohol Consumption: Limiting alcohol intake helps maintain liver health and supports NAD+ production, as excessive alcohol can deplete NAD+ levels.

NAD supplements recap

• Purpose: NAD supplements aim to boost NAD+ levels in the body, which supports cellular energy production, DNA repair, and various metabolic processes.
• Common Forms: The most common NAD supplements include nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), both of which are precursors to NAD+.
• Potential Benefits: NAD supplementation may enhance energy levels, improve cognitive function, support mitochondrial health, aid in DNA repair, and promote healthy ageing.
• Effectiveness: While initial studies suggest benefits, more research is needed to fully understand the long-term effects and efficacy of NAD supplements.
• Natural Alternatives: NAD+ levels can also be supported through diet, regular exercise, intermittent fasting, healthy sleep, and reducing alcohol consumption.

Remember, it’s recommended you speak with your doctor for personalised advice before starting NAD supplementation.

Symptoms of High Blood Sugar

Signs of high blood sugar include extreme thirst, frequent urination, fatigue, weakness, blurred vision, and unintended weight loss.

High blood sugar often results from illness, stress, excessive consumption of sugary or starchy foods, and missed doses of diabetes medication.

Causes of High Blood Sugar

Common causes of elevated blood sugar include:

• Illness: Infections and illnesses can cause blood sugar levels to rise.
• Stress: Physical or emotional stress can increase blood sugar.
• Diet: Consuming large amounts of sugary or starchy foods can lead to spikes.
• Sedentary Lifestyle: Lack of physical activity can contribute to higher blood sugar levels.
• Medication: Missing doses or not taking diabetes medication as prescribed can impact blood sugar control.

NAD FAQs

References:

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