There are two main ways to provide the nutrients and myriad of compounds that can help your body operate at its best and improve both lifespan and healthspan. One is to include foods and adjust your diet, however, we don’t always have that option to due various constraints such as taste and lifestyle. This is where supplements step in to provide the essential components of those foods as extracts or via chemical synthesis.

Here we explore the supplements you can incorporate into your lifestyle to get those identified goodies that keep us healthy for longer. This is the second of three articles on increasing health and life span. Our article on foods will have some overlap with this article as in many cases supplements are a derivative of food.
As always, we do our best to validate any information presented however, we cannot guarantee the accuracy of statements made here and does not constitute medical advice. Please check with your healthcare professional before making changes to your diet and lifestyle.
We have included as many references as possible to back our claims and for you to click into to investigate further for yourself. We encourage anyone seeking to improve their health via supplementation to take some time to research it’s effects, side effects and dosage.

Mitochondrial support

Mitochondria are organelles, basically, little functional units within cells, much like an organ is to our body. They provide power to our cells by delivering ATP to the cells and are thought to once be free-ranging bacteria. It is thought that the break down of mitochondrial function is one of, if not the main contributor to ageing. We’ve used SelfHacked and SelfDecode in many of our references as they often provide useful information such as dosage and side effects. Please ensure you click through and take some time to understand each one before you add anything to your routine and, as always, speak to your doctor or health care professional before making any diet or lifestyle changes.

So, what can we do to support mitochondria? Supplements that show to be beneficial for mitochondria include:

• Oxaloacetate is part of the body’s energy system and some research indicates longevity properties. In animal studies, it was found to significantly increase lifespan. ((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988682/))((https://febs.onlinelibrary.wiley.com/doi/abs/10.1016/0014-5793(80)80446-7))((https://pdfs.semanticscholar.org/312d/d1265a0a54312b44e44d615e3fe14ee29666.pdf))
• Carnatine or L-Carnatine or Acetyle-L-Carnatine or ALCAR, is an amino acid found naturally in the body. It is believed to play a critical role in the body’s energy systems. It’s also purported to support liver and brain function.((https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.490230414)) It can also help improving cognitive decline((https://europepmc.org/abstract/med/3781687)), ageing((http://www.academia.edu/download/44345547/Ames_20Delaying_20Aging_20with_20ALCAR.pdf)) and cardiovascular health.((https://europepmc.org/abstract/med/7808246))((https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2007-1024754))
• Malic Acid is found in many fruits and first found in apple juice. It’s also generated by our body naturally. It’s shown to help with skin conditions and improve fatigue and pain associated with fibromyalgia.¹((https://www.ncbi.nlm.nih.gov/pubmed/25674699))
• Resveratrol was also mentioned in our food article as being found in grapes and the driver behind reports of red wine being “healthy”. It activates AMPK and SIRT1 which also qualifies it for our autophagy section. This would be one of the key anti-ageing supplements in any longevity stack.²((http://www.mdpi.com/2076-3921/8/3/74))((http://www.e-crt.org/journal/view.php?number=328))((https://www.nature.com/articles/nature05354))((https://www.sciencedirect.com/science/article/pii/S1550413108001824))((https://www.sciencedirect.com/science/article/pii/S155041311200143X))
• Apigenin is found in fruits and vegetables and has been shown to help calm nerves and provide antioxidant effects. It has been shown to lower fatty acids and cholesterol in animal models and increase NAD+ levels.((http://www.ncbi.nlm.nih.gov/pubmed/23172919))((https://www.ncbi.nlm.nih.gov/pubmed/25106896))
• Leucine is an amino acid often used and sold as a body building supplement. It has shown promise in brain function related to liver disease and recovery from exercise.((https://www.ncbi.nlm.nih.gov/pubmed/23172919)) It’s also been linked with SIRT1 activation.((https://www.ncbi.nlm.nih.gov/pubmed/22185590)) Leucine also inproves mitochondrial function.((https://www.ncbi.nlm.nih.gov/pubmed/23812674))
• Nicotinamide or Niacin has evidence that it can decrease LDL and increase HDL.³((http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804877/))((http://www.ncbi.nlm.nih.gov/pubmed/22085343)) It can also lower triglycerides and total cholesterol.⁴((http://www.ncbi.nlm.nih.gov/pubmed/24768191))
• PQQ or Pyrroloquinoline has been identified as a co-factor for enzyme reactions.((http://neoraingredients.com/wp-content/uploads/2017/04/Pyrroloquinoline-Quinone-PQQ-Combined.pdf)) Among it’s benefits, it’s been shown to activate genes related to mitochondrial growth.((https://www.ncbi.nlm.nih.gov/pubmed/20491655)) We do generate it in our body naturally also.⁵
• Lipoic Acid is an antioxidant⁶ and is synthesised by mitochondria.⁷
• Berberine is often seen as a more natural alternative to Metformin with less side effects. It helps with glucose regulation and activates SIRT3 and AMPK.⁸ It has also shown promise in reducing total cholesterol and LDL.⁹
• Bitter Melon contains charantin, polypeptide-p and vicine which, have been shown to lower blood sugar.
• Nicotinamide Mononucleotide (NMN) is the best known precursor of NAD+ right now and also reduces levels of inflammatory cytokines.((https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.14878)) NAD+ decreases as we age so supporting it should help minimise the effects of ageing.((https://www.sciencedirect.com/science/article/pii/S1550413116302443)) It increases mitochondrial NAD+ levels which supports cell health and repair.((https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.24397?af=R))¹⁰((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027280/))
• Nicotinamide Riboside (NR) is a derivative of Nicotinamide or B3 and is another precursor of NAD+¹¹
• Gotu Kola((https://www.sciencedirect.com/science/article/pii/S104345261500056X)) is used in Tai-Chi as a longevity herb. It enhances CREB¹² and may help improve blood flow.¹³.
• Gynostemma is another Chinese herbal medicine with similar effects as panax ginseng. Benefits include anti-inflammatory, antioxidative((https://www.sciencedirect.com/science/article/pii/S0144861706003559)), and even antitumor.¹⁴
• Inosine may improve cognitive function and decrease ageing induced oxidative stress.((https://link.springer.com/article/10.1007/s10787-018-0476-y)) It may also protect against memory impairment induced by Alzheimer disease.((http://link.springer.com/article/10.1007/s00213-019-05419-5))
• C60 aka Buckminsterfullerene((https://link.springer.com/content/pdf/10.1038/318162a0.pdf)) is a man made carbon compound with 60 carbon atoms. It’s a very new molecule and there’s not much research on it but it has been shown to act as an antioxidant((https://www.sciencedirect.com/science/article/pii/S0041008X08000057)) and possible anticancer effects.((https://www.sciencedirect.com/science/article/abs/pii/S0009279711003243)). Early reports showed toxicity but this is beleived to be due to impurities and pure c60 seems to have little to no side effects.((http://www.mdpi.com/1996-1944/12/16/2571)).
• CoQ10 is present in living cells naturally. It acts as a co-factor for ATP production.((https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1002/biof.5520320124)) It’s commonly available as a health food supplement and has been for more than 20 years. It also acts as an anti-inflammatory.((https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1473-2165.2006.00220.x))
• Butyrate was mentioned in our foods article. It helps reduce inflammation, supports glucose regulation and also supports cognitive function. It may also improve insulin sensitivity and increase energy expenditure.((https://diabetes.diabetesjournals.org/content/58/7/1509.short))
• Hydroxytyrosol acts as an antioxidant((https://www.sciencedirect.com/science/article/pii/0278691584900334)) and may increase mitochoindrial generation via SIRT1, AMPK and PPAR-alpha increase.((https://www.ncbi.nlm.nih.gov/pubmed/25885653))
• N-acetyl cystine (NAC) is a powerful antioxidant, supports glutathione, and helps liver damage repair. It may even help prevent some cancers((https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.240531040)) and HIV.((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC54223/)) It has also shown beneficial for bi-polar((https://www.sciencedirect.com/science/article/pii/S0006322308005003)) and schizophrenia.((https://www.nature.com/articles/1301624))
• Succinc Acid or Succinate may boost mitochondrial energy and act as an antioxidant.((https://www.nature.com/articles/nature11986)) It is part of the citric acid cycle and may also help recovery from injury.((https://www.nature.com/articles/nature13909/))
• Chinese Skullcap antioxidant that also contains amino acids, fatty acids and minerals as well as plant sterols.((http://feeds.rsc.org/~r/rss/ra/~3/LUpEUol44Lc/C9RA03229K)) There are reports of liver toxicity from this supplement so beware and monitor your ALT levels.((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409358/))((https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1592/phco.30.7.750))
• Creatine can increase strength((https://www.sciencedirect.com/science/article/pii/S0899900718303617?dgcid=rss_sd_all)), muscle mass((https://www.physiology.org/doi/abs/10.1152/jappl.1996.81.1.232)) and post-exercise recovery when used with workouts. It supports ATP and may also support cognitive function.((https://journals.lww.com/acsm-msse/Fulltext/1998/07000/Creatine_supplementation_in_endurance__sports.16.aspx))
• HMB or Beta-hydroxy beta-methybutyrate, supports exercise performance((https://stars.library.ucf.edu/etd/4819/)) and muscle growth as well as preventing muscle loss due to ageing and may help lower cholesterol.((https://repositories.lib.utexas.edu/handle/2152/75182))
• Danshen is the root of Salvia militiorrhiza and is a popular Chinese cardio herbal drug((http://www.onlinejacc.org/content/47/7/1498.1.abstract)). It improves microcirculation which causes vasodilation of coronary arteries. It also shows potential in activation of SIRT3((http://www.jbc.org/content/280/14/13560.short)), PGC-1alpha((https://www.ncbi.nlm.nih.gov/pubmed/17108241))((https://www.physiology.org/doi/full/10.1152/advan.00052.2006)) and AMPK.((https://www.ncbi.nlm.nih.gov/pubmed/22996345))((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627054/))
• Caffeic Acid acts as an antioxidant((https://pubs.acs.org/doi/abs/10.1021/jf970055t)) and is found in plants.
• EGCG is found in green tea and is believed to be responsible for the touted health benefits of green tea.((https://www.sciencedirect.com/science/article/abs/pii/S0031942206003530)) It has antioxidant effects as well as cardiovascular support, cancer prevention and weight loss. It also impacts mitochondrial biogenesis, ATP production and apoptosis.((https://www.ncbi.nlm.nih.gov/pubmed/26731017)) It’s even been shown to help with control of cholesterol levels.((http://www.sciencedirect.com/science/article/pii/S0304416518301673))
• Curcumin is the active compund in tumeric. Curcumin as a supplement is more bioavailable than tumeric. It’s an antioxidant and anti-inflammatory((https://pubs.acs.org/doi/abs/10.1021/mp700113r#))¹⁵ It can also help protect against food pathogens and cancer cells.((https://journals.sagepub.com/doi/abs/10.1177/0883911519863074?ai=2b4&mi=ehikzz&af=R))
• Methylene Blue may help reverse cognitive impairment((http://link.springer.com/article/10.1186/s40478-019-0856-6)) and inhibits nitric oxide((https://europepmc.org/article/MED/7679577)) which may help in treatment of anaphylactic hypotension((https://europepmc.org/article/MED/17941276)). As a longevity drug it shows promise in improving cellular and mitochondrial function.((https://www.ncbi.nlm.nih.gov/pubmed/28840449)) It also acts as an MAOI so should be avoided or used under supervision with SSRI‘s.((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265679/))
• Biotin also known as B7 is involved with metabolisation of fatty acids, amino acids and carbohydrates.((https://www.ncbi.nlm.nih.gov/pubmed/22869039)) It also plays a role in gene expression of enzymes involved with biotin utilisation in human cells.((https://www.ncbi.nlm.nih.gov/pubmed/15992685))((https://www.sciencedirect.com/science/article/abs/pii/S095528630300130X))((https://academic.oup.com/jn/article/133/3/716/4688036))
• Forskolin has been used in Indian ayurvedic medicine since ancient times. It has been used to treat hypertension, heart failure, eczema, colic, respiratory disorders, insomnia and convulsions. Clinical studies have confirmed this use for treating asthma, angina, psoriasis and cancer metastases.((https://www.ajol.info/index.php/ecajps/article/view/107098))((https://www.sciencedirect.com/science/article/abs/pii/S0165614789800082)) It has also been shown to assist with fat derived stem cell therapy((https://bmcmolcellbiol.biomedcentral.com/articles/10.1186/1471-2121-11-25)) and to assist with fat burning.((https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X.2011.00908.x))((https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2005.162)) On top of that it may also increase DNA repair.((https://www.sciencedirect.com/science/article/pii/S0022202X15340665))
• Potassium may, among other things, assist with glucose metabolism((https://europepmc.org/abstract/med/1619503))((http://www.metabolismjournal.com/article/0026-0495(80)90074-8/abstract)) and blood pressure.((https://www.physiology.org/doi/full/10.1152/ajprenal.1999.276.3.F476))¹⁶
• He Shou Woo (Pronounced her shou woo) aka Fo-ti is a popular Chinese herbal medicine touted as the longevity herb((https://www.sciencedirect.com/science/article/pii/S0378874114007922)). It is an antioxidant((https://www.sciencedirect.com/science/article/pii/S030881460700249X)), can prevent hair loss((http://doi.org/10.1155/2018/1380146)) and improve cognitive performance((https://www.worldscientific.com/doi/abs/10.1142/s0192415x03000862)). Beware to always find prepared He Shou Woo as the raw root has been shown to be toxic to the liver.((https://www.sciencedirect.com/science/article/pii/S0367326X11003261))((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240794/))
• MSM or Methylsulfonylmethane is a natural compound found in some green veggies and in the human body as well as animals and milk((https://patents.google.com/patent/US4616039A/en)).((https://draxe.com/nutrition/msm-supplement/)) It’s often taken to help with reduction of chronic pain((https://www.sciencedirect.com/science/article/pii/S0965229919306417?dgcid=rss_sd_all)) and osteoarthritis.((https://www.sciencedirect.com/science/article/pii/S1063458405002852))((https://link.springer.com/article/10.2165/00044011-200424060-00005)) It’s also been shown to induce apoptosis in some cancers((https://www.sciencedirect.com/science/article/pii/S1382668918304812?dgcid=rss_sd_all))
• AKG or Alpha-ketoglutarate is an amino acid that regulates amino acid synthesis and helps with energy production.¹⁷
• Alpha-GPC supports choline in the body which is essential for the brain and, as a result is a popular nootropic supplement. Choline in this form also builds acetylcholine which is a neurotransmitter supporting cognitive function.((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782876/))((https://www.ncbi.nlm.nih.gov/pubmed/24156263))
• D3 is known as the sunshine vitamin. Humans, as well as many animals, make D3 from sunlight via the skin. You may think you get enough, especially here in Australia but, you may be wrong((https://www.deakin.edu.au/research/research-news/articles/vitamin-d-deficiency-strikes-one-third-of-australians)). Between hours spent indoors, under shade and using sunscreen((https://academic.oup.com/jcem/article-abstract/64/6/1165/2653261)) it’s been shown that many people are deficient in vitamin D((https://osteoporosis.org.au/vitamin-d))((https://www.health.gov.au/resources/pregnancy-care-guidelines/part-g-targeted-maternal-health-tests/vitamin-d-status)). It supports bone health and affects insulin((https://europepmc.org/article/med/12800453)). Your skin also looses its ability to produce vitamin D as we age((https://www.jci.org/articles/view/112134)) and may help improve ageing skin((http://www.mdpi.com/1999-4923/11/7/311)).
• K2 Mk7/mk4 can improve insulin sensitivity((https://care.diabetesjournals.org/content/34/9/e147.short)) and prevent bone loss((https://onlinelibrary.wiley.com/doi/abs/10.1359/jbmr.2000.15.3.515))((https://link.springer.com/article/10.1007/s00198-013-2325-6)).
• Maca((https://www.sciencedirect.com/science/article/pii/S0308814619303942?dgcid=rss_sd_all)) is a root vegetable native to the Andes in Peru. It’s used there as a medicine for various benefits and was used by Inca warriors.((https://www.sciencedirect.com/science/article/pii/S0378874117323516)) It may improve male fertility((https://www.tandfonline.com/doi/full/10.1080/14786419.2019.1698572))((http://www.asiaandro.com/archive/1008-682x/3/301.htm?wsixufbzrsrgdnrp?dxuoarpvhvqgklwz)) and acts as an antioxidant((https://www.sciencedirect.com/science/article/pii/S0308814602001334)). Maca also acts on the endocannabinoid system and activates the CB1 receptor which is also activated by CBD via one of it’s components, Anandamide.
• Astragalus is a traditional Chinese herbal medicine((http://altmedrev.com/archive/publications/3/5/338.pdf)) used for treatment of hepatitis and cancer amongst other things. It has been shown to help in reducing obesity, heptatic steatosis, neuroinflammation and cognition impairment((http://doi.org/10.3390/ijms18122746)). It is also reported to increase adipose thermogenesis((http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111/bph.14139)) and possible anti-tumour effects((https://www.sciencedirect.com/science/article/pii/S0304383506006665)).
• Olive leaf extract contains polyphenols to support the scavenging of reactive oxygen species and may help with preventing heart disease((https://academic.oup.com/jn/article-abstract/140/5/946/4689063)) and regulation of blood sugar.((https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0031-1299970))
• Phosphatidylcholine is a foundation molecule used in human cells and supports the liver, gut mircobiome((https://www.nejm.org/doi/full/10.1056/nejmoa1109400)) and mental health.¹⁸ It may also extend lifespan((http://www.hindawi.com/journals/omcl/2019/286064)).

Autophagy and Senolytics

Put simply, autophagy is the process by which our cells do spring cleaning. Senolytics are molecules that help senescent cells to be discarded and recycled. Senescent cells are cells that are no longer healthily dividing via apoptosis.

• Fisetin is found in fruit, but more so in strawberries by a large factor((https://www.leafscience.org/fisetin/)). It’s a reasonably well researched senolytic((https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689181/)). It can assist with cancer treatments and neuroprotection((https://www.sciencedirect.com/science/article/pii/S156757690700389X)) as well as cytokine suppression¹⁹ and anti-inflammatory action in human mast cells((https://www.sciencedirect.com/science/article/abs/pii/S1043661806001848)).
• Sulphoraphane is found in broccoli and other cruciferous vegetables. It has shown to have antioxidant effects and in protecting against cancers. It activates NRF2 pathways((https://www.sciencedirect.com/science/article/pii/B9780128142530000061)) and reduces risk of neurodegenerative disease, ocular cancer, respiratory problems, heart disease and more.((https://wellnessmama.com/346041/sulforaphane/))

Microbiome

There are many overlaps with the microbiome as it does have links to many facets of our health and nutrition. It makes sense right? This is where our food goes after we chew and swallow it and it gets broken down by the stomach. It’s where our body absorbs much of its nutrients. There are two main types of bacteria in the gut, firmicutes and Bacteroides and, you want a good balance of these two.

Pre-biotics

Prebiotics are foods that support the bacteria in our guts. They assist bacteria by providing the compounds and molecules they need to flourish. If we do not support our gut bacteria, no matter how many new ones we introduce, they simply won’t survive and be healthy.

• Modified Citrus Pectin is Pectin derived from citrus that has been modified to have shorter chains and be more easily digestible((https://www.mdpi.com/2072-6643/11/11/2619)). It has many purported benefits including inhibition of cancer cells((https://academic.oup.com/jnci/article/94/24/1854/2906798))((https://www.nature.com/articles/4500679))((https://journals.sagepub.com/doi/abs/10.1177/1534735410369672)), however, for general health and longevity we are interested in it’s support of gut bacteria as fibre((https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2672.2002.01719.x))((https://www.sciencedirect.com/science/article/pii/S0022283614003957))((https://pubs.acs.org/doi/abs/10.1021/jf2053959)). In this form it supports many of the bacteria in our microbiome that assist with mitochondrial health and general health.
• Ellagic Acid is found in fruits such as pomegranate and berries, and acts as an antioxidant((https://www.sciencedirect.com/science/article/pii/S0098299710000749)) as well as inducing apoptosis((http://ar.iiarjournals.org/content/26/5A/3601.short)). It can also help limit the proliferation of cells such as cancer cells((https://www.sciencedirect.com/science/article/pii/S0955286304001226)).

Pro-biotics

Pro-biotics are additional bacteria that we introduce to our gut. We do this if we have reason to believe our own population has died out or not healthy, or, perhaps they simply don’t have a long life. Either way, it’s important to understand that this is only part of the equation and that, simply dumping more bacteria in our gut, isn’t always the best approach. pro-biotics are good for improving the biodiversity of our gut bacteria species.

• L. Reuteri (Lactobacillus reuteri) produces B12((https://jb.asm.org/content/185/18/5643.short)), antibacterial substances((https://www.tandfonline.com/doi/abs/10.3109/08910608909140210))((https://www.sciencedirect.com/science/article/pii/S1075996408000231)), can help reduce colic((https://pediatrics.aappublications.org/content/126/3/e526.short)) and a raft of other health benefits((https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053867&__hstc=171738815.e835c34ab7bf88e972fdd7a7debc8575.1477699200065.1477699200066.1477699200067.1&__hssc=171738815.1.1477699200068&__hsfp=1773666937))((https://www.wageningenacademic.com/doi/abs/10.3920/BM2013.0042)) such as hair health((https://patents.google.com/patent/US20180256490A1/en))
• Bacillus subtilis has recently been identified to improve longevity((https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.1111/1751-7915.12048))((https://www.ncbi.nlm.nih.gov/pubmed/28134244))

As you now know, there are many supplements that are shown or suspected to assist in longevity and general health. They won’t all work for you and some may not work at all as we learn more about them. The best advice we can give is to only add 1 at a time and give your body time to respond so that you can learn how it is interacting and impacting your body. Keep a journal and makes notes on how you feel, quality of sleep, energy levels, eating habits and more. This will help you go back and see what supplements worked and which didn’t. As you build your stack, you should remove supplements that are not doing anything for you and add in new ones as you learn about the effect and doses for each.

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