Selected Supplements for Immunity, Energy, Long-term Cognition, and Health Span.

First considerations: dietary supplements have not been used for most of human history. There are areas of the world where people live extraordinary long, healthy lives. They do not achieve this by taking dietary supplements.


Dietary Supplements | FDA


Nutrients required for the function of longevity proteins constitute a class of vitamins that are here named “longevity vitamins.” Such nutrients play a dual role for both survival and longevity. The following 10 compounds may be classed as putative longevity vitamins: taurine, the fungal antioxidant ergothioneine; the bacterial metabolites pyrroloquinoline quinone (PQQ) and queuine; and the plant antioxidant carotenoids lutein, zeaxanthin, lycopene, α- and β-carotene, β-cryptoxanthin, and the marine carotenoid astaxanthin. Because nutrient deficiencies are highly prevalent in the United States (and elsewhere), appropriate supplementation and/or an improved diet could reduce much of the consequent risk of chronic disease and premature aging.

Alpha-ketoglutarate (AKG)

An intermediate of tricarboxylic acid cycle alpha-ketoglutarate (AKG) is involved in pleiotropic metabolic and regulatory pathways in the cell, including energy production, biosynthesis of certain amino acids, collagen biosynthesis, epigenetic regulation of gene expression, regulation of redox homeostasis, and detoxification of hazardous substances. AKG supplement was found to extend lifespan and delay the onset of age-associated decline in experimental models such as nematodes, fruit flies, yeasts, and mice.


  • Acute resistance exercise increases plasma AKG levels and muscular AKG synthesis.
  • AKG induces muscle hypertrophy and fat loss in vivo in mouse obesity models.
  • AKG activates the adrenal gland, enhancing enhanced thermogenesis and lipolysis.


According to David Sinclair, AKG can reverse age markers in mice by affecting the Yamanaka factors.


Many of the studies advocating the use of AKG have been  poorly done, as pointed out by Dr Brad Stanfield in this video.


Supplemental AKG is available on Amazon. Being strongly acidic, it is always combined with calcium or arginine to form a salt.


Antioxidant Supplements

Antioxidant supplements (vitamin C, vitamin E, and beta carotene) can block any adaptations to exercise. There is also evidence that such supplements may promote cancer and otherwise shorten lifespan.

Vitamin B12

Vitamin B12 should be taken by anyone middle aged or older, regardless of diet. B12 is best taken sublingually, or, at least, chewed. Symptoms of B12 deficiency are many and can be attributed to other causes. Among B12 deficiency symptoms are dreadful neurological problems and stroke.

Beta Alanine

Two studies investigating the benefits of β-alanine supplementation on the tactical performance of soldiers found it to be effective in maintaining lower body power and psychomotor performance, with cognitive function improvements also observed.

Study: The Effect of β-Alanine Supplementation on Performance, Cognitive Function and Resiliency in Soldiers. Image Credit: wavebreakmedia /


Betaine, also known as trimethylglycine, is found in foods such as beets, spinach, and whole-grain breads. Betaine can enhance the effects of exercise and and also lower homocysteine.


Meta-analysis of five studies: Supplementation with at least 4g/d of betaine for a minimum of 6 weeks can lower plasma homocysteine.


Do not take beta carotene

Beta Carotene supplements have long been shown to be detrimental, and may even trigger cancer. Carotenes from foods is the way to go. Dr. Roger Seheult again shows this in is (well documented) video.



Choline is an essential nutrient that is naturally present in some foods and available as a dietary supplement. Choline is a source of methyl groups needed for many steps in metabolism. The body needs choline to synthesize phosphatidylcholine and sphingomyelin, two major phospholipids vital for cell membranes. Choline supplementation appears to be safe as long as one B12 and folate is adequate.


Severe choline deficiency results in DNA strand breaks in rodents, alterations to epigenetic markers and histones, and affects brain development ().


When consuming choline-rich red meat, TMAO is formed from bacterial metabolism of choline via an intermediate, trimethylamine. 


People of Okinawa get along nicely (are long-lived) with 300 mg of daily dietary choline. A plant-based diet supplies plenty of choline.

Vitamin C

Vitamin C is categorized as a survival vitamin because, in addition to being an antioxidant, it also functions as a cofactor for survival proteins. A quality plant-based diet will supply plenty of vitamin C.


The following six carotenoids account for 95% of the carotenoids found in American blood and brain: lutein, zeaxanthin, lycopene, α- and β-carotene, astaxanthin, and β-cryptoxanthin. There is good evidence that these carotenoids help optimize a healthy lifespan: low intake of these carotenoids has been associated with all-cause mortality, macular degeneration and associated blindness, cognitive decline, CVD, various types of cancer, metabolic syndrome, oxidative damage to DNA, high blood pressure, hearing loss, decreased visual acuity, inflammation, immune decay, and cognitive decay.


Some carotenoids are available as supplements. The best way to enjoy carotenoids is with a quality plant-based diet.




We don’t have evidence to show that people don’t get enough chromium. Or that, if they are low in it, that it causes health problems. Do not supplement chromium.


Creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson’s, Huntington’s disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy.


Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66–76 years).

Curcumin from turmeric

Curcumin causes the elongation of the lifespan of model organisms, alleviates ageing symptoms and postpones the progression of age-related diseases in which cellular senescence is directly involved.


Are Curcumin and Turmeric the Same Thing? - Drink ZYN


Investigations on curcumin with regard to aging and age-associated disease in model organisms has described that curcumin and its metabolites, prolong the mean lifespan of some aging model organisms such as C. elegansD. melanogaster, yeast, and mouse. It has been proposed to have several biological activities, such as antioxidative, anti-inflammatory, anticancer, chemopreventive, and anti-neurodegenerative characteristics. In several studies on various model organisms it has been shown that the lifespan extension via curcumin treatment was connected with enhanced superoxide dismutase (SOD) activity, and also declined malondialdehyde (MDA) and lipofuscin levels. As well as the pivotal role of curcumin on the modulating of major signaling pathways that influence longevity of organisms like IIS, mTOR, PKA, and FOXO signaling pathways.


Nematodes grown on media containing curcumin showed a significantly increased lifespan by reducing the production of reactive oxygen species. The lifespan extension of Drosophila by curcumin supplementation was associated with increased superoxide dismutase (SOD) activity, and decreased lipofuscin and malondialdehyde levels. Curcumin up-regulated expression of SOD genes and down-regulated expression of several age-related genes. The positive effects of curcumin on lifespan extension likely arise from beneficial regulation of common oxidative stress responses and age-related genes. 


The ability of curcumin to mitigate the expression levels of age-associated genes in young flies suggests that the action of curcumin on these genes is a cause, rather than an effect, of its life span-extending effects.


Curcumin is best known for it’s ability to help prevent Alzheimer’s.


Curcumin is fat-soluble. Too much curcumin can cause anemia. Consuming curcumin with piperine from black pepper can increase absorption up to 2000%.

Vitamin D

Extensive evidence shows that vitamin D deficiency causes—or has been associated with—a large number of diseases that affect healthy aging, such as all-cause mortality, cancer, cardiovascular disease (CVD), diabetes, brain function, and so forth.


From the standpoint of memory disorders, vitamin D plays a role in clearing a protein called beta-amyloid, which accumulates in the brain in people with AD. It may also help to protect nerve cells from injury, including from other abnormal proteins that play a role in dementia.

DHA/EPA (fish oil)

DHA/EPA are present in high levels in the central nervous system and are important for brain and retinal structure and function. The role of DHA in aging, Alzheimer, Parkinson, schizophrenia, bipolar, and depression have been recently reviewed (). Low EPA and DHA levels in red blood cells were found to be associated with increased all-cause mortality in a study of 6,501 elderly women followed for 14.9 y (). A meta analysis reported that each 1% increase in plasma DHA/EPA was linked with a 20% decreased risk in all-cause mortality ().


Low blood levels of DHA/EPA were shown in a 5-y study to be associated with a faster rate of telomere shortening, a marker of cell aging (). Supplemental fish oil (2.5 g/d) slowed telomere shortening and lowered biomarkers of oxidation in older adults (). Daily supplemental DHA (2 g/d) increased the rate of clearance of amyloid plaques in people with mild cognitive impairment (). DHA/EPA are important for vitamin D steroid hormone effectiveness ().


This video by Dr. Rhonda Patrick shows the amazing benefit of Ω-3 fats for cognitive health. Ω-3 fats (and vigorous exercise) help preserve the tiny capillaries in the brain. Ω-3 fats also benefit the blood-brain barrier.


Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.


Vitamin E supplements are not recommended

From this video (with references): Taking vitamin E supplements can push levels to that which the body cannot handle. Cochrane warns that vitamin E supplements may increase mortality. We also have no data on benefits or harms of toctrienol supplementation.


Dr. Roger Seheult, MD shows in this video (with lots of references) that vitamin E from foods in incredibly beneficial, unlike vitamin E supplements.





 Ergothionine is synthesized by most mushrooms, cyanobacteria, and many types of soil bacteria (73, 74), but not by plants or animals. It is present in high concentrations in mitochondria, a major source of oxidants, and it has been suggested that it may be a longevity vitamin.


5 Reasons to Eat More Mushrooms | U.S. News


Fiber is sometimes considered as a supplement, but is better as part of a high-fiber plant-based diet.


Cochrane: Dietary fibre can prevent cardiovascular disease.


Glutathione reduces genomic damage, oxidative stress, chronic inflammation, insulin resistance and insulin levels. Glutathione improves mitochondrial functioning and muscle strength and other ageing hallmarks.


Increasing glutathione levels lowers Alzheimer’s pathology and improves cognitive decline. GlyNAC supplementation for 24-weeks in older adults was well tolerated and lowered oxidative stress, corrected intracellular glutathione deficiency and mitochondrial dysfunction, decreased inflammation, insulin-resistance and endothelial dysfunction, and genomic-damage, and improved strength, gait-speed, cognition, and body composition.


Glutathione deficiency due to ageing or illness can be corrected by dietary cysteine (N-acetlyl cysteine or NAC) and glycine (GlyNAC) supplementation. For a 70 kg person, this means 7g of glycine and 9.3g of NAC. This may also increase autophagy.


One problem with NAC is that it can block sulforaphane-caused autophagy. NAC has a half-life of 6.25 hours.


Sulforaphane can increase brain glutathione by 30%. Healthline presents other ways to increase glutathione. Exercise increases glutathione in older individuals. Aerobic + resistance training produced the largest increase in glutathione.




NMN (nicotinamide mononucleotide) may


be useful for older individuals.



In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. Taurine depletion affects longevity and cellular senescence; an effect possibly linked to a disturbance in protein folding. A decline in circulating taurine is a feature of aging in multiple species, including monkeys and humans, with levels falling by ∼80% over the human life span. They further found that mice lacking the major taurine transporter had shorter adult life spans.


Taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis.


Taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. Taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis.


 Most of taurine is acquired from the diet, mainly from fish and other seafood, seaweed, eggs, and dark-meat poultry. So vegans need to supplement. Here is a SciShow video about taurine. Phsionic covers it well here.

PQQ ( pyrroloquinoline quinone)

Pyrroloquinoline quinone (PQQ) is incredibly beneficial – see this blog post on mitochondrial health. PQQ supplements are available, but it is silly to take any when so many wonderful foods, mentioned in that blog post, provide PQQ.


Mitochondria influence or regulate a number of key aspects of aging, and suggest that strategies directed at improving mitochondrial quality and function might have far-reaching beneficial effects. There are pleiotropic effects of mitochondrial dysfunction in aging. To the rescue: Exercise, curcuminoids, and PQQ. There is no need to supplement PQQ if one consumes PQQ-rich foods: parsley, green peppers, kiwi fruit, papaya and tofu. These foods contain about 2-3 mcg per 100 grams. Green tea provides about the same amount per 120 mL serving. Here is a comprehensive list of PQQ-rich foods.


PQQ is important for diabetes, antioxidant activity, neuroprotection, cognition, and lowering the level of C-reactive protein (i.e., inflammation). In addition, PQQ supplementation improved antioxidant potential and decreased the levels of mitochondrial-related intermediates and metabolites in urine, providing support for previous studies that demonstrated that PQQ improved mitochondrial efficiency


Mg deficiency affects about 45% of the United States population and has been associated with increased all-cause mortality, poor DNA repair capacity, increased risk of lung cancer and various other kinds of cancer, heart disease, telomere shortening, and risk of stroke. Magnesium deficiency is a principal driver of cardiovacular disease, a worldwide under-recognized problem, and thus that it is a major public health crisis (). Mg is required to convert vitamin D to its active steroid hormone form.


Melatonin for sleep, and to keep one’s marbles


The neuroprotective effects of melatonin have been tested in many different animal models. These include models of Parkinson’s disease, Alzheimer’s disease, stroke and chemical toxicities. The outcome of these studies provides highly promising evidence that melatonin will prove to be very important in reducing loss of neurons and glia under pathophysiological conditions. The results of clinical trials performed within the last half decade support this conclusion.


Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with Aβ. Our studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation.


The USPSTF recommends against the use of beta carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements for the prevention of cardiovascular disease or cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of single- or paired-nutrient supplements (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. 


Most people would be better off just drinking a full glass of water and skipping the vitamin. There are some exceptions, however. Highly restrictive diets and gastrointestinal conditions, or certain weight-loss surgeries that cause poor nutrient absorption, are examples of reasons why a multivitamin or individual vitamins might be recommended.


Resveratrol is not recommended

From this video (with references): resveratrol does not activate SIRT1, and will blunt adapation to exercise.


Sulforaphane is awesome. Suforaphane supplements are available, but one the Rhona Patrick mentioned is $100 for a 90 day supply at 10mg per capsule. 100 g of broccoli sprouts will get you 40 mg of sulforaphane for a small fraction of the cost. This blog post has additional information on sulforaphane along with sprouting suggestions.

Urolithin A

Urolithin A (UA) has many benefits. Urolithin A is not found directly in the food we eat. It is a postbiotic which can be produced naturally from a diet that includes pomegranates, berries, and walnuts since they are a great source of the polyphenols your gut converts into UA.


Plants contain a large number of bioactive chemicals, which are present in our diets, as for example 8,000 different flavonoids (). Flavonoids function as “nature’s pesticides,” the purpose of which is to protect plants from predators (); many have beneficial (or toxic) effects in humans at some dose and may function by inducing hormetic mechanisms ().


By Otto

I am a health enthusiast, engineer, and maker.