Longevity Bundle A

Resveratrol

What is Resveratrol?

Resveratrol is a polyphenol produced by plants to act as a natural defence mechanism against environmental stressors. In humans, resveratrol has raised attention for being an effective antioxidant and for positively affecting the cells in the body, leading to a number of health benefits. Since its discovery, researchers have published more than 12,000 scientific papers about resveratrol, and over 200 human clinical trials involving this polyphenol have been conducted to date.

Where can it be found in nature?

Resveratrol can be found in Japanese knotweed and in a variety of foods, including peanuts, blueberries, and raspberries. It is also (somewhat famously) present in red wine as it gets concentrated from the skin of red grapes. It is produced in large quantities through microbial fermentation or extraction from Japanese knotweed for supplement use.

What are its primary functions and benefits?

In plants, resveratrol acts as a barrier against harsh environments. Scientific evidence suggests that it does the same for humans by working to protect the body’s cells and support healthy ageing. Published research and clinical data indicate that resveratrol supports bone health, cardiovascular health, blood glucose levels, healthy cognitive function, skin youthfulness, and oral health.

Resveratrol has also been shown to penetrate cells and help rejuvenate the mitochondria, again, helping to support healthy ageing. Mitochondria are the powerhouses that create energy inside every cell in our bodies. However, as we age, the mitochondrial function slowly impairs. This leads to the decline of many systems in our body as we get older, including cardiovascular, cognitive, skin, and bone systems. Resveratrol helps reverse or slow this process.

Part of the healthy ageing benefits of resveratrol can be explained by the activation of sirtuins, a family of enzymes that play a critical role in DNA repair. Resveratrol activates a specific sirtuin-coding gene called SIRT1 which results in gene expression and metabolic pathway activation, both of which are excellent for your energy levels and overall health.

Why do we use resveratrol in our supplements?

We have included resveratrol in our Booster for its ability to activate SIRT1. Ideally, this is taken in combination with our NMN product. NMN and resveratrol work synergistically to improve metabolic health and slow down the ageing process. NMN increases NAD+ levels and provides NAD+ to all seven sirtuins, while resveratrol provides additional SIRT1 activation to further mediate DNA repair. In addition, the activation of sirtuins by NAD+ regulates essential physiological processes, such as the circadian rhythm, glucose and fat metabolism, and normal ageing.

Another reason we’ve chosen resveratrol is that it is an apigenin bioenhancer, which is also present in our Booster. This lets the ingredients complement one another. Co-administration of apigenin and resveratrol allows more apigenin to survive liver metabolism, which results in more than twice the plasma apigenin levels (compared to using apigenin alone).

As an enzyme that breaks down our NAD+ levels, CD38 can accelerate ageing. Thankfully, apigenin can help prevent this NAD+ breakdown, so getting more apigenin into the body is invaluable in reducing the effects of CD38.

Sources

1. Ramírez-Garza, S. L., Laveriano-Santos, E. P., Marhuenda-Muñoz, M., Storniolo, C. E., Tresserra-Rimbau, A., Vallverdú-Queralt, A., & Lamuela-Raventós, R. M. (2018). Health Effects of Resveratrol: Results from Human Intervention Trials. Nutrients, 10(12), 1892. https://doi.org/10.3390/nu10121892
2. Thaung Zaw, J. J., Howe, P. R., & Wong, R. H. (2021). Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study. Clinical nutrition (Edinburgh, Scotland), 40(3), 820–829. https://doi.org/10.1016/j.clnu.2020.08.025
3. Moraes, D. S., Moreira, D. C., Andrade, J., & Santos, S. (2020). Sirtuins, brain and cognition: A review of resveratrol effects. IBRO reports, 9, 46–51. https://doi.org/10.1016/j.ibror.2020.06.004
4. Lee, J. A., Ha, S. K., Cho, E., & Choi, I. (2015). Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin. Nutrients, 7(11), 9650–9661. https://doi.org/10.3390/nu7115485

Ubiquinol (CoQ10)

What is Ubiquinol (CoQ10)?

Ubiquinol is the active, bioavailable form of Coenzyme Q10 (CoQ10). CoQ10 is naturally present in the body (about 95% as Ubiquinol and 5% as Ubiquinone) and acts similarly to a vitamin in its biological functions. But, by definition, ubiquinol is not a vitamin since it can be synthesised by human cells. 

It is a powerful antioxidant and plays a major role in producing energy in cells. Research has revealed CoQ10’s wide range of health benefits. Unfortunately, concentrations decline as you age as well as through fatigue, strenuous exercise, smoking, illness, and even some medications. Thankfully, you can restore your CoQ10 levels with the help of dietary supplements.

Where can it be found in nature?

You can find CoQ10 in meats including, pork, beef, chicken, fatty fish, and organ meat, vegetables such as broccoli, cauliflower and spinach, fruits such as oranges and strawberries, as well as in legumes, sesame seeds, pistachios and peanuts. The CoQ10 you find in supplements is manufactured via a natural yeast fermentation process and is highly-effective.

What are its primary functions and benefits?

CoQ10 has an essential role in supplying all your cells with energy. It’s involved in making adenosine triphosphate (ATP), whose production happens within the mitochondria. To put it simply, CoQ10 acts as a fuel additive that optimizes mitochondrial performance, extracting the most energy with the least damage. Your mitochondria need to burn fuel cleanly and efficiently to assure their own integrity and your own longevity. Studies have shown that animals, from primitive worms to laboratory mice, enjoy dramatic extension of their life spans when supplemented with mitochondrial-protecting CoQ10, which suggests that it has important longevity benefits for humans, too.

Additional benefits from CoQ10's mitochondrial energy-boosting effects include protection from neurodegenerative diseases and mental health disorders, heart and vascular health support, enhanced lung function, healthy blood cholesterol levels and protection from the effects of elevated glucose in diabetes and metabolic syndrome. CoQ10 also has an important role as an antioxidant, protecting cell membranes from oxidative damage caused by free radicals.

Why do we use ubiquinol in our supplements?

We’ve included ubiquinol in our Booster supplement as it is the active, more bioavailable, antioxidant form of CoQ10—it’s ready for immediate use by the body. Ubiquinol is an ideal complement to our NMN product  (a potent NAD+ precursor) since ubiquinol works in synergy with NAD+ to support energy-production and mitochondrial health in every cell of your body. It’s important to note that your body doesn’t store CoQ10. Therefore, to see continued benefits, it's essential to keep up a supplement routine.

Sources

1. Yamamoto, Y., & Yamashita, S. (1997). Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Molecular aspects of medicine, 18 Suppl, S79–S84. https://doi.org/10.1016/s0098-2997(97)00007-1
2. Hernández-Camacho, Juan D et al. Coenzyme Q10 Supplementation in Aging and Disease. Frontiers in Physiology. 2018; 9(44) https://doi.org/10.3389/fphys.2018.00044
3. Castro-Marrero, J., Sáez-Francàs, N., Segundo, M. J., Calvo, N., Faro, M., Aliste, L., Fernández de Sevilla, T., & Alegre, J. (2016). Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial. Clinical nutrition (Edinburgh, Scotland), 35(4), 826–834. https://doi.org/10.1016/j.clnu.2015.07.010
4. Skarlovnik, A., Janić, M., Lunder, M., Turk, M., & Šabovič, M. (2014). Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. Medical science monitor : international medical journal of experimental and clinical research, 20, 2183–2188. https://doi.org/10.12659/MSM.890777

Pterostilbene

What is Pterostilbene?

Pterostilbene is a polyphenol. "Phenol" refers to a particular chemical structure (in this case, a hydroxyl group linked to a benzene ring), while "poly" means that the molecules can have more than one structure. It is a resveratrol analogue but is approximately 4x easier for the gut to absorb, making it even more effective than resveratrol.  

Where can it be found in nature?

Pterostilbene is found naturally in several plants, fruits, and nuts, including blueberries, almonds, and grape leaves. It is also found in grapes but, unlike resveratrol, doesn't survive the wine-making process.

What are its primary functions and benefits?

In plants, pterostilbene functions by combating pathogens, including microbes and parasites. When consumed by humans, it serves as a powerful antioxidant. Moreover, recent studies have shown that it has a number of additional benefits, including boosting cognitive function, preventing cell death in the brain, reducing blood sugar, lowering blood pressure, reducing inflammation, and protecting the liver, heart, and eyes.

Recently, scientists have discovered that pterostilbene can increase dopamine in the brain by blocking monoamine oxidase B (MAO-B). Increased dopamine can enhance mood and lower anxiety. It could also help to improve cognition and memory. 

In one study, rodents given pterostilbene observed an increase in new cell growth in the brain's memory centre. Next to providing a brain boost, studies have also uncovered pterostilbene's very promising anti-ageing potential. Pterostilbene activates SIRT1, also known as one of the "longevity genes" encoding sirtuins, a family of enzymes involved in cell damage protection and DNA repair.

Why do we use pterostilbene in our supplements?

We have included pterostilbene in our Booster (link to Booster) for its ability to activate SIRT1. Taken in combination with our NMN product, it can help to improve metabolic health and slow down the ageing process. NMN increases NAD+ levels and provides NAD+ to all seven sirtuins, while pterostilbene provides additional SIRT1 activation to further mediate DNA repair. In addition, sirtuins activation by NAD+ regulates critical physiological processes such as the circadian rhythm, glucose and fat metabolism, and healthy ageing.

Sources

1. McCormack, D., & McFadden, D. (2013). A review of pterostilbene antioxidant activity and disease modification. Oxidative medicine and cellular longevity, 2013, 575482. https://doi.org/10.1155/2013/575482
2. Grabowska, W., Sikora, E. & Bielak-Zmijewska, A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology 18, 447–476 (2017). https://doi.org/10.1007/s10522-017-9685-9

Apigenin

What is Apigenin?

Apigenin is a common and widely distributed flavonoid found in a variety of plants. Flavonoids are a class of naturally occurring phytochemicals that are found in plant tissues. Plants use flavonoids to protect themselves from environmental stress, including stress from pathogens and radiation from the sun.

Where can it be found in nature?

Apigenin can be found in chamomile, yarrow, thyme, cherries, tea, olives, broccoli and parsley (especially dried parsley). However, it’s much easier to get a worthwhile amount when taking it in supplement form.

What are its primary functions and benefits?

Apigenin supports healthy ageing. It isn’t just good at protecting plants from external aggressions; it can protect humans as well. Apigenin is an antioxidant, anti-inflammatory, neuroprotective, and cognition-enhancing substance. It has exciting potential in the treatment and prevention of Alzheimer's disease. And, a number of scientific studies have shown apigenin inhibits CD38, one of the main NAD+ degrading enzymes in human tissues.

During ageing, CD38 levels increase in several tissues (including the liver, brain, heart, and kidney), which leads to age-related NAD+ decline. Moreover, increased levels of CD38 during ageing correlate with the development of mitochondrial dysfunction, mediated by reduction of Sirtuin3 and NAD+ activity. Apigenin inhibits CD38 and increases intracellular NAD+ levels, improving the overall healthy functioning of the cellular body.

Why do we use apigenin in our supplements?

We include apigenin in our Booster supplement as it prevents NAD+ decline in the body, thanks to its CD38 inhibiting properties. It's a perfect complement to our NMN product since NMN acts as a direct precursor (a building block) of NAD+, while apigenin slows down and inhibits the breakdown of your NAD+ storage supply. In other words, NAD+ levels can rise when you take apigenin and NMN together. They work as a powerful, healthy ageing combination. If that's not enough, activating sirtuins by NAD+ regulates essential physiological processes, including the circadian rhythm, glucose and fat metabolism, and the healthy ageing process.

Sources

1. Barbosa MT, Soares SM, Novak CM, Sinclair D, Levine JA, Aksoy P, Chini EN. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. FASEB J. 2007; 21:3629–39. https://doi.org/10.1096/fj.07-8290com
2. Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, O'Neil L, White TA, Sinclair DA, Chini EN. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2013; 62:1084–93. https://doi.org/10.2337/db12-1139
3. Ogura Y, Kitada M, Xu J, Monno I, Koya D,. CD38 inhibition by apigenin ameliorates mitochondrial oxidative stress through restoration of the intracellular NAD+/NADH ratio and Sirt3 activity in renal tubular cells in diabetic rats. Aging (Albany NY). 2020; 12:11325-11336. https://doi.org/10.18632/aging.103410

Betaine

What is Betaine?

Betaine, also called Trimethylglycine (TMG), is a substance created in the body. It's a derivative of the amino acid glycine and has vitamin-like effects and properties. Betaine is involved in liver function and cellular reproduction. It also supports the production of carnitine and helps your body metabolise the amino acid homocysteine.

Where can it be found in nature?

You can find betaine in a variety of food sources, including sugar beets, wheat bran, rye, bulgur, spinach, quinoa, brown rice, sweet potato, turkey breast, beef, veal, and some seafood. Its name is derived from the word beets, as this is where it was initially discovered.

What are its primary functions and benefits?

Betaine has two primary functions in the human body. First, betaine acts as a "methyl donor," distributing methyl groups around your body. A methyl group is a special kind of hydrogen and carbon molecule that induces a process called methylation. Methylation is a critical component of various physiological processes, including protein function, RNA processing, and the regulation of genes.

Second, betaine is an osmolyte. As an osmolyte, betaine regulates osmosis by creating a fluid level balance inside and outside your body's cells. Imbalanced fluid levels can result in cellular rupture or cellular shrinkage. A major imbalance can cause the cell to die, so betaine's positive effects on the body's fluid levels is crucial in helping keep cells healthy and living.

On the whole, betaine has a number of health benefits. Evidence shows that betaine is a critical nutrient for protecting and enhancing the function of internal organs and improving vascular health. It may also support digestive function, heart health, liver function and detoxification, fat loss, and muscle mass improvement.

Why do we use betaine in our supplements?

We included betaine in our Booster (link to Booster) to support the body's natural NAD+ production (link to NAD+ page) and to complement the NMN supplement (link to NMN). NAD+ is consumed and broken down into nicotinamide (NAM) and converted into methyl nicotinamide (MeNAM) in the energy production cycle. Supplementation of NMN (or other NAD+ precursors) produces a high amount of methyl nicotinamide. Betaine is an excellent methyl donor and is ideal for supplementation while taking NAD+ precursors to enhance the body's internal methylation pool.

Sources

1. Zhao G, He F, Wu C, et al. Betaine in Inflammation: Mechanistic Aspects and Applications. Front Immunol. 2018;9:1070. Published 2018 May 24. doi:10.3389/fimmu.2018.01070
2. Sun W, Zhai M, Li D, et al. Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels. Clin Nutr 2017;36:1136-1142.

NMN

What is NMN?

NMN, short for nicotinamide mononucleotide, is a naturally occurring vitamin B3 derivative. NMN is a precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme present in all human cells. NAD+ is essential for life and is linked closely to metabolism and ageing. 

Where can it be found in nature?

NMN is naturally present in our food, including milk, meat, avocado, broccoli, cabbage, cucumber, and edamame. However, it would be nearly impossible to get an efficient dose from food alone. You’d need to consume almost 100kg of broccoli or 416kg of beef just to get 250mg of NMN, the dose provided in our daily supplement.

What are its primary functions?

NMN becomes NAD+ in our bodies, and NAD+ is involved in hundreds of metabolic processes throughout the body. Its most crucial roles include helping turn nutrients into energy and working as a fuel for the enzymes involved in DNA protection and repair. Accumulating evidence suggests that NAD+ systemically declines with age and contributes to the development of age-related diseases. A 50-year-old, for example, has roughly half the levels of NAD+ as a 20-year-old. Of course, you can live with low levels of NAD+, but it will accelerate the ageing process and reduce your healthspan. Fortunately, increasing NAD+ levels has many health benefits for various organs, including the brain, cardiovascular system, and skin elasticity.

What are the benefits of taking NMN?

NMN targets the natural decline of NAD+ in our bodies as we age. By restoring NAD+ levels, NMN supplements help you regain, sustain, and maintain vibrant health and energy through the years. A number of studies have shown the beneficial effects of NMN on energy levels, memory, blood vessel health, metabolism, stem cell health, epigenome maintenance, and DNA damage repair. In a clinical study in 2014, for instance, a team of researchers led by Dr. David Sinclair, professor of genetics at Harvard Medical School and expert on biological ageing, demonstrated that NMN can extend lifespan, and a later study showed that NMN increases NAD+ levels and reverses DNA damage.

Why do we use NMN in our supplements?

NMN is one of the most promising supplements for slowing ageing. Since NMN gets converted into NAD+ in our cells, it can effectively replenish NAD+, helping you regain your health and energy to youthful levels. NMN is proven to be safe, stable, and effective. Continuous clinical trials demonstrate and unveil more of its benefits.

Sources

1. Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell metabolism, 27(3), 529–547. https://doi.org/10.1016/j.cmet.2018.02.011 
2. North, B. J., Rosenberg, M. A., Jeganathan, K. B., Hafner, A. V., Michan, S., Dai, J., Baker, D. J., Cen, Y., Wu, L. E., Sauve, A. A., van Deursen, J. M., Rosenzweig, A., & Sinclair, D. A. (2014). SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. The EMBO journal, 33(13), 1438–1453. https://doi.org/10.15252/embj.201386907 
3. Li, J., Bonkowski, M. S., Moniot, S., Zhang, D., Hubbard, B. P., Ling, A. J., Rajman, L. A., Qin, B., Lou, Z., Gorbunova, V., Aravind, L., Steegborn, C., & Sinclair, D. A. (2017). A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science (New York, N.Y.), 355(6331), 1312–1317. https://doi.org/10.1126/science.aad8242 
4. Kiss, T., Nyúl-Tóth, Á., Balasubramanian, P., Tarantini, S., Ahire, C., Yabluchanskiy, A., Csipo, T., Farkas, E., Wren, J. D., Garman, L., Csiszar, A., & Ungvari, Z. (2020). Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects. GeroScience, 42(2), 527–546. https://doi.org/10.1007/s11357-020-00165-5
5. Yoshino, M., Yoshino, J., Kayser, B. D., Patti, G. J., Franczyk, M. P., Mills, K. F., Sindelar, M., Pietka, T., Patterson, B. W., Imai, S. I., & Klein, S. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science (New York, N.Y.), 372(6547), 1224–1229. https://doi.org/10.1126/science.abe9985