Beyond avoiding processed junk food, vegans can sometimes forget that they need to be smart about the supplements they choose. It’s a fact of life that our depleted soil and indoor lifestyles can mean we’re not consuming enough vitamins in general. Most of the adults I see in my clinic, whether they follow a vegan diet or not, lack important nutrients. To make up for these deficiencies, here’s the vegan supplements I take to be healthy. (And here’s a hint! The first three on the list are the most important.)
1. Vitamin B12
Vitamin B12 is important for our brain, nerves and blood health. It’s also part of methylation, the process that regulates homocysteine levels and plays an important role in controlling DNA regulation. Our bodies do not make B12 naturally (neither do plants). It’s made by bacteria that live in the gastrointestinal tract of other animals. When animal products are eaten, B12 is ingested.
By some estimates, 50 percent of vegans and 10 percent of vegetarians are deficient in vitamin B12. Because such a large percentage of people are lacking this crucial vitamin, this is an essential vegan supplement. I recommend taking about 2,500 ug of B12 once a week, or 250 ug daily, ideally as a liquid, sublingual or chewable form, for better absorption. And just so we’re clear—there is no known risk in taking a bigger amount of B12.
2. Vitamin D
Vitamin D promotes bone health and is essential in blood pressure and blood glucose control, heart function and brain health. In a study of more than 65,000 England residents, researchers found that vegans had higher levels of fiber, magnesium and vitamins E and C than their meat-eating counterparts. However, they had lower levels of vitamin D.
Direct sunlight on the skin for 20 to 30 minutes a day can give you enough vitamin D, but if you’re not outside, you’ll want to supplement. Vitamin D3 is the form most people use, but it comes from animal sources, such as lanolin, which means it isn’t suitable for vegans. Vegan supplement versions of D3 are also available. I recommend 800 IU a day.
Deficiencies in omega-3s are common regardless of the diet. Because fish isn’t an option for vegans, I usually recommend people take a combined DHA and EPA supplement (the fatty acids that are great for heart and brain health), derived from algae. I tell most patients on a vegan diet to supplement with 250 mg each day while limiting foods rich in omega-6, which may contribute to inflammation. These are mainly in the forms of oils such as corn, soy, safflower, sunflower and vegetable oil blends. Overall, just go easy or skip oils for cooking. Finally, add whole foods rich in ALA, the precursor to EPA and DHA. Perfect vegan sources of omega-3s are leafy greens, or 1 to 2 tablespoons a day of ground flaxseeds, a small handful of English walnuts, or chia seeds.
L-carnitine is an amino acid that plays an important role in fueling energy production in the heart and other muscles. Because it’s mainly found in meat, vegetarians have lower levels of it in their muscles. There are also rare reports of heart disease in patients who lack it. Although long-term studies of L-carnitine as a supplement are not available, I recommend a vegan supplement with 500 mg a day—particularly if you’re athletic or have heart disease. I advise patients who have elevated TMAO levels not to take L-carnitine supplements, because it’s is unfavorable for artery health.
Taurine is the most abundant amino acid in the body,and it’s most frequently associated with energy drinks. It’s important for the cardiac immune systems, insulin action, hearing and electrolyte balance. Taurine is typically found in meat and seafood, so vegans often don’t have enough. I recommend vegans supplement with 500 mg a day.
6. Vitamin K2
Vitamin K2 directs calcium to bones, rather than the arteries, and vitamin K2 works well with vitamin D to promote strong bones and a healthy heart, but it’s also hard to find in plant foods. Our bodies can convert the vitamin K1 found in dark leafy greens to K2, but it’s not clear just how much is being converted. Vitamin K2 can be found in sauerkraut, plant-based kefir, unpasteurized kombucha, vegan kimchi and natto. As our bodies age, there is a reduction in vitamin K2 production, so I recommend that an adult vegan supplement.. There are a number of vegan supplements available, and I suggest adding 50 to 100 ug of vitamin K2 to your diet each day.
Vegan diets are an amazing choice for health, promoting a clean planet and being mindful of animals’ lives. Vegan diets are supported by thousands of medical research studies, and they are endorsed by the United Nations, Oxford University, the USDA Food Guidelines and the Association of Nutrition and Dietitians, but vegan supplements are a key part of health for these non-meat eaters.. Although it may seem annoying to add so many supplements to your daily routine, it’s critical that you’re a “smart vegan” and ensure your body is getting what it needs every day to function at its best.
When in doubt – go without.
Safety is never a guarantee and supplements do not come without risk. Even the most natural supplements in the form of herbs or something as unassuming as vitamin C can contain heavy metals, contaminants, and other byproducts from processing. Supplementing without an intimate knowledge of the biochemical pathways of your body can result in a disruption of hormones and can even mess up neurotransmitter production. Just because some of these are sold at the supermarket doesn’t mean they’re foolproof.
In many cases, excessive nutrients are eliminated in the urine, but in other instances, it’s better to go without than to take something your body does not want or need.
Creating your individualized supplement regimen.
Everyone’s ideal supplement profile is different, and should be carefully customized to your body based on your symptoms, health history and goals. But to make things as simple as possible, here’s a breakdown of supplements that most everyone should be taking.
For each nutrient, you will get a:
- Dosage recommendation.
- The correct form it should be taken in.
- The time it should be taken.
- A recommended brand.
I have no relation or affiliation with any of these companies. They are simply the ones I trust with my health and use on a daily basis. Note: I am not a doctor, so seek medical advice from your personal physician prior to supplementing.
Here are the 10 nutrients (almost) everyone should supplement with.
- Vitamin D
- Vitamin K2
- Vitamin C
- Krill Oil
- Vitamin A
- Folinic Acid with B12
First and foremost: Vitamin D. As the most important supplement, Vitamin D influences more than 1,000 different genes and serves as a cofactor for sex hormones like testosterone, human growth hormone, and estrogen. It plays a role in immunity, regulating inflammation, calcium metabolism, and bone development. It’s no coincidence this is one of the few vitamins the human body can synthesize on its own. It’s true – you can get plenty of vitamin D from sun exposure, but for non-nudist, non-equatorial dwellers, relying on the sun alone is probably not sufficient. Because this is a fat-soluble vitamin, it is important to test your vitamin D levels before dosing at levels more than 1,000-2,000 IU. Too much vitamin D in supplement form can lead to toxicity.
Dose: 1,000 IU / 25 pounds of body weight.*
Time Taken: Morning
Recommended Brand: Jarrow Formulas D31
*People with darker skin tones don’t convert sunlight into vitamin D as readily as lighter skinned people. If you’re brown skinned, a safe bet is more like 1,500 IU / 25 pounds of body weight, but you should always test your blood levels because individual response to dosage varies.
Magnesium is used in over 300 enzymatic processes in your body, including all of those involved in ATP (cellular energy) production. It’s also essential for DNA and RNA transcription.
Magnesium deficiency is a serious problem in the U.S. and can contribute to conditions like cardiovascular disease, diabetes, asthma, anxiety disorders, and PMS. Symptoms of magnesium deficiency include heart arrhythmias, tachycardia, headaches, muscle cramps, nausea, metabolic syndrome, migraines, and many more. Almost all Americans are at least a little deficient in magnesium. Due to the depletion of minerals and other nutrients in our soil and and poor farming practices, it’s almost impossible to get enough magnesium from food sources alone. Bottom line: everyone should probably supplement with magnesium. Start with 200 mg and work your way up to tolerance. Some forms of magnesium can cause loose stools.
Dose: 300-800mg / day
Forms: Citrate, malate, glycinate, threonate, or orotate
Time Taken: Before bedtime.
Recommended Brand: Life Extension
Unless you grew up eating only grass-fed meat and raw milk, you’re likely deficient in vitamin K2. Vitamin K2 is a fat-soluble vitamin essential to calcium metabolism, which helps to ward off atherosclerotic conditions and heart attacks, as well as increase bone strength. We get vitamin K1 from leafy green vegetables, and vitamin K2 from grass-fed animal products. Humans don’t convert vitamin K1 into K2 efficiently. You should consume a total of at least 2,000 mcg per day of K2, at least 100 mcg of which should be the MK-7 form.
Dose: 2,000mcg / day (100mcg MK-7 form)
Forms: MK-4, and MK-7
Time Taken: Doesn’t really matter, but it’s best to take this with vitamin D, so morning is best.
Recommended Brand: Life Extension
Raise a glass to vitamin C, which is high on the spectrum of both safe and effective. We need vitamin C to form collagen and connective tissue. It’s also used to synthesize the potent antioxidant glutathione. Vitamin C can enhance immune function and help fend off free radical damage. It’s often challenging to get enough vitamin C from the diet alone and your body is constantly using and excreting it. Some fruits and vegetables are high in vitamin C, but cooking and storage methods can diminish vitamin C content. I recommend supplementing with at least 1,000 mg per day. Take more if you’re battling an infection or injury.
Dose: 1,000-2,000 mg / day
Forms: Ascorbic acid crystals or time-release capsules.
Time Taken: Morning and evening, but it’s best not to take it after a workout as isolated antioxidants can negate the insulin sensitivity gained from exercise.
Recommended Brand: Solaray
When you hear iodine, think thyroid function. Your thyroid needs iodine to function properly. It also promotes immune function and protects against neurological damage. Given that most of the population is iodine deficient, I advocate supplementation. Food sources include seafood and iodized salt, but still this may not be adequate. Iodized salt won’t get you optimal levels and is often highly processed anyway, which can include heavy metals and other contaminants from processing. For iodine supplementation, a good starting point is 1 mg from kelp powder or as potassium iodide. Iodine should be supplemented along with selenium, as they work together to support thyroid function. If you suffer from a thyroid condition, talk to your doctor before supplementing with iodine, as it can sometimes make things worse.
Dose: 1mg / day
Forms: Kelp powder or potassium iodide capsules
Time Taken: Doesn’t matter.
Recommended Brand: Pure Encapsulations potassium iodide
EPA/DHA (Krill oil)
This is a tricky one. Here, quality and dosage are key. Small doses of high quality fish oil reduce inflammation, improve brain function, and even enhance muscle growth, but poor quality or high doses can cause more problems than they help to solve. If you can’t find a quality fish oil, forget about it and just steer clear. Better yet, eat some low-mercury, wild fish 2-3 times per week. I recommend krill oil over fish oil altogether since it’s more stable. In its phosphorylated form, it’s much more efficient for the brain to use. It’s also rich in astaxanthin, a potent antioxidant.
There are real benefits to taking EPA and DHA, but most of these are strongest if your diet is deficient in omega-3s, or too high in omega-6’s. If you’re eating a Bulletproof Diet, this won’t be a problem. Humans only need 350mg of DHA and EPA a day for optimal brain function. If you’re eating grass-fed meat and wild caught fish, you can easily achieve this. Otherwise, you should supplement with at least 1,000 mg of krill oil per day.
Dose: 1,000mg / day
Forms: Krill Oil
Time Taken: With meals.
Recommended Brand: Jarrow Krill oil
In addition to these basic supplements, there are a few you should also consider taking.
If you aren’t eating organ meats, you’re likely deficient in vitamin A, which is an integral cofactor for numerous metabolic reactions and bodily functions. Keep in mind: plants sources contain beta-carotene, NOT vitamin A. Beta-carotene does get converted into vitamin A in the body, but some people are more efficient at this than others. So, if you’re not eating organ meat or are a vegan or vegetarian, you’re more likely to be deficient in this important fat-soluble vitamin. Again, vitamin A is a fat-soluble vitamin, so over supplementation can cause toxicity.
Dose: 10,000-15,000 IU / day.
Forms: Retinol (A good source of vitamin A is cod liver oil, which also has vitamin D)
Time Taken: With meals.
Recommended Brand: Green Pasture Fermented Cod Liver Oil (Arctic Mint flavor)
This important nutrient supports immunity, can be anti-carcinogenic, fends off neurodegenerative disease, and safeguards the thyroid. Although it is possible to consume sufficient amounts of selenium from wild caught fish and grass-fed animal products, the reality is that most of us do not. In these cases, supplement with 200 mcg per day. Caution though: in excessively high amounts, selenium can cause toxicity.
Dose: 200 mcg / day
Forms: Se Methyl Selenocysteine or selenomethionine
Time Taken: Doesn’t matter.
Recommended Brand: Life Extension
Zinc and copper go together in your body like bacon and eggs. Zinc is a powerful and essential mineral involved in countless aspects of cellular metabolism. It plays a major role in your immune function, protein and DNA synthesis, and wound healing.
Copper is needed for proper vascular and heart function. With a majority of the population taking in a meager 0.8 mg daily, most of the U.S. does not get enough copper. Zinc and copper intake has fallen over the last century due to new farming and dietary practices. Zinc is found in higher levels in foods like oysters, herring, beef, lamb, pork, liver, egg yolks, carrots, beets and cabbage. And if you’re eating at least four ounces of beef liver per week, you can meet your copper needs. Other good sources of copper include cocoa (dark chocolate – look for low toxin Bulletproof Chocolate Powder), cashews, and lobster. If you don’t feel like you’re getting adequate zinc and copper from food or if you suffer from a compromised immune system, you should supplement with at least 10mg zinc and 1mg of copper per day.
Dose: 10-15mg zinc and1mg copper / day
Forms: Zinc picolinate / Capsule form of copper
Time Taken: Doesn’t matter.
Recommended Brand: Pure Encapsulations
B-12 and folic acid
Vitamin B12 is a common deficiency, which is a shame since B12 can protect against dementia and depression, boost the immune system, optimize nerve function and signaling, protect against atherosclerosis, repair DNA and regenerate cells. B12 lowers homocysteine and protects against atherosclerosis. It’s absolutely essential for brain function.
Folate deficiency can also lead to neurological issues. Folate and B12 are vastly intertwined, and both are required for mental function. One deficiency will cause another, but folate will not correct a B12 deficiency. If you make the mistake of treating B12 deficiency with folate, you may suffer permanent brain damage. Vegans, please take note: you can only get B12 naturally from animal products, so if you don’t eat meat or animal byproducts, you must supplement. Likewise, high amounts of folate without adequate B12 can cause neurological conditions. Therefore, it is important to take these two together. Indeed, they go hand in hand.
Dose: >5mg of methylcobalamin or hydroxycobalamin and >800mcg of folate (5-MTHF or folinic acid, NOT folic acid)
Time Taken: Doesn’t matter.
Recommended Brand: varies
The optimal supplementation regime varies from individual to individual. It is inextricably linked with preexisting diet and lifestyle factors. As a general rule of thumb, get the majority of nutrients from your diet. Food delivers nutrients in their most natural, “perfect” forms. When you do supplement – you absolutely get what you pay for. Remember, the key here is quality.
What’s Missing in Vegetarian Diets?
Vegetarians are often deficient in vitamin B12, and those who avoid meat have long been advised to supplement with B12. While vegetarians are slightly more likely to suffer anemia than are meat eaters, this does not by itself explain why they do not enjoy greater longevity in their later years.
A fascinating paper recently published in the journal Mechanisms of Aging and Development presents an entirely new theory to explain why vegetarians do not live longer.41 It turns out that those who avoid eating beef suffer a deficiency of a nutrient (carnosine) that is critical to preventing lethal glycation reactions in the body.
For the benefit of new members, glycation can be defined as the toxic binding of glucose to the body’s proteins. Glycation alters the body’s proteins and renders them non-functional. While wrinkled skin is the first outward appearance of glycation, most degenerative diseases are affected in one way or another by pathological glycation reactions.
Diabetics suffer from accelerated glycation that contributes to the secondary diseases that result in premature death.42,43 For instance, glycation’s destructive effect on the arterial system results in a loss of elasticity, hypertension, and atherosclerosis.44-47 Glycation is involved in disorders as diverse as cataract, cancer, and Alzheimer’s disease.48-57
Unless aggressive steps are taken, many aging adults will suffer the devastating effects of glycation to proteins throughout their bodies. This fact was established recently when it was shown that even healthy people with slightly elevated glycation levels are at higher risk for heart attack.
Vegetarians have higher levels of advanced glycation end products (AGEs) in their blood compared to those who eat meat.58,59 This is because an exclusively vegetarian diet would lack carnosine, nature’s most potent anti-glycating agent.
For vegetarians who fastidiously adhere to a diet devoid of meat, their “Achilles’ heel” may be lack of carnosine. This was confirmed in a paper published in October 2005 titled, “Glycation, ageing and carnosine: Are carnivorous diets beneficial?”41è
41. Hipkiss AR. Glycation, ageing and carnosine: Are carnivorous diets beneficial? Mech Ageing Dev. 2005 Oct;126(10):1034-9.
How Does Carnosine Work?
The proteins in our bodies are the substances most responsible for our ability to function and sustain life. Glycation causes the destruction of these proteins. Once too many proteins lose their ability to function, the body becomes prone to degenerative diseases and premature aging.63 Carnosine has been shown to specifically protect against age-related degradation of protein.
Protein degradation occurs as a result of cross-linking and the formation of advanced glycation end products (AGEs). These changes figure prominently in the process of aging and in its typical manifestations, such as skin wrinkling and brain degeneration.62,64,65 Carnosine is effective against cross-linking and the formation of AGEs.66,67 Glycated proteins produce 50 times more free radicals than nonglycated proteins, and carnosine may be the most effective anti-glycating agent known.
An example of carnosine’s defense against protein degradation can be seen when proteins are exposed to toxic malondialdehyde (MDA).68 Similar to formaldehyde, MDA causes protein cross-linking and formation of AGEs. Carnosine has been shown to inhibit MDA-induced glycation in blood albumin and eye-lens protein.69,70 Carnosine has also been shown to keep MDA from inducing protein cross-linking.71 One study showed that carnosine actually decreased MDA levels in mice.72
Carnosine’s Effects on the Brain
Carnosine is highly concentrated in the brain, owing to the fact that the brain uses carnosine to protect against cross-linking, glycation, excitotoxicity, and oxidation. Animal studies show that carnosine provides broad protective effects in simulated ischemic stroke.73
Abnormal copper and zinc metabolism stimulates senile plaque formation in Alzheimer’s disease.74,75 Chelators of these metals dissolve plaques in the laboratory. Carnosine is a potent copper-zinc chelating agent that can inhibit the cross-linking of amyloid beta that leads to brain-cell plaque formation. A signature of Alzheimer’s disease is impairment of the brain’s arterial and capillary system. Carnosine has been shown to protect the cells that line the brain’s blood vessels from damage by amyloid beta as well as from damaging byproducts of lipid oxidation and alcohol metabolism.76
Carnosine Extends Cellular Life Span
Our bodies comprise cells that replace themselves by dividing. There is a genetic limit as to how many times our cells will continue to replicate themselves via healthy division processes. Once enough cells reach their genetic reproductive limit, the organism (the human body) is no longer able to sustain life functions and succumbs to disease or death. Carnosine appears to extend the period of time that cells will continue to divide in a youthful manner.
Laboratory research suggests that carnosine is able to rejuvenate cells approaching the end of the life cycle, restoring normal appearance and extending cellular life span.77,78 When scientists transferred late-passage fibroblasts (a type of connective tissue cell) to a culture medium containing carnosine, the cells exhibited a rejuvenated appearance and often an enhanced capacity to divide.79 The carnosine medium increased life span, even for old cells. Cells transferred to the carnosine medium attained a life span of 413 days, compared to 126-139 days for the control cells. This study showed that carnosine induced a remarkable 67% increase in cellular life span.
These aged cells also grew in the characteristic patterns of young cells, and resumed a uniform appearance in the presence of carnosine. However, when the aged cells were transferred back to a medium lacking carnosine, signs of senescence quickly reappeared. How does carnosine revitalize cells in culture? Some researchers propose that carnosine may rejuvenate cells by reducing the formation of abnormal proteins or by stimulating the removal of old proteins.69
Why Aging Adults Need Carnosine
Life Extension members have long known that carnosine levels in the body decline with age. Muscle carnosine levels in our bodies decrease 63% from age 10 to age 70, which may account for the reduction in muscle mass and function seen in aging adults.80 Carnosine acts not only as an antioxidant in muscle, but also as a pH buffer.81 In this way, it keeps on protecting muscle cell membranes from oxidation under the acidic conditions of muscular exertion. Carnosine enables the heart muscle to contract more efficiently through enhancement of calcium response in heart cells.82 Muscle levels of carnosine correlate with the maximum life span of animal species.
Carnosine has been shown to rejuvenate connective tissue cells,77,79 which may explain its beneficial effects on wound healing. Damaged proteins accumulate and cross-link in the skin, causing wrinkles and loss of elasticity. Carnosine is the most promising broad-spectrum shield against protein degradation.
62. Quinn PJ, Boldyrev AA, Formazuyk VE. Carnosine: its properties, functions and potential therapeutic applications. Mol Aspects Med. 1992;13(5):379-444.
63. Stadtman ER. Protein oxidation and aging. Science. 1992 Aug 28;257(5074):1220-4.
64. Bierhaus A, Hofmann MA, Ziegler R, Nawroth PP. AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept. Cardiovasc Res. 1998 Mar;37(3):586-600.
65. Munch G, Schinzel R, Loske C, et al. Alzheimer’s disease—synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J Neural Transm. 1998;105(4-5):439-61.
66. Hipkiss AR, Michaelis J, Syrris P. Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross- linking agent. FEBS Lett. 1995 Aug 28;371(1):81-5.
67. Munch G, Mayer S, Michaelis J, et al. Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of beta-amyloid peptide. Biochim Biophys Acta. 1997 Feb 27;1360(1):17-29.
68. Hipkiss AR, Chana H. Carnosine protects proteins against methylglyoxal-mediated modifications. Biochem Biophys Res Commun. 1998 Jul 9;248(1):28-32.
69. Wang AM, Ma C, Xie ZH, Shen F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc.). 2000 Jul;65(7):869-71.
70. Brownson C, Hipkiss AR. Carnosine reacts with a glycated protein. Free Radic Biol Med. 2000 May 15;28(10):1564-70.
71. Hipkiss AR, Preston JE, Himswoth DT, Worthington VC, Abbot NJ. Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells. Neurosci Lett. 1997 Dec 5;238(3):135-8.
72. Yuneva MO, Bulygina ER, Gallant SC, et al. Effect of carnosine on age-induced changes in senescence-accelerated mice. J Anti-Aging Med. 1999;2(4):337-42.
73. Boldyrev AA, Stvolinsky SL, Tyulina OV, et al. Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals. Cell Mol Neurobiol. 1997 Apr;17(2):259-71.
74. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci. 1998 Jun 11;158(1):47-52.
75. Lee JY, Friedman JE, Angel I, Kozak A, Koh JY. The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice. Neurobiol Aging. 2004 Nov;25(10):1315-21.
76. Hipkiss AR, Preston JE, Himsworth DT, et al. Pluripotent protective effects of carnosine, a naturally occurring dipeptide. Ann NY Acad Sci. 1998 Nov 20;854:37-53.
77. McFarland GA, Holliday R. Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res. 1994 Jun;212(2):167-75.
78. Hipkiss AR, Michaelis J, Syrris P, et al. Strategies for the extension of human life span. Perspect Hum Biol. 1995;1:59-70.
79. McFarland GA, Holliday R. Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts. Exp Gerontol. 1999 Jan;34(1):35-45.
80. Stuerenburg HJ, Kunze K. Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle biopsies and rat muscles. Arch Gerontol Geriatr. 1999 Sep;29(2):107-13.
81. Burcham PC, Kerr PG, Fontaine F. The antihypertensive hydralazine is an efficient scavenger of acrolein. Redox Rep. 2000;5(1):47-9.
82. Zaloga GP, Roberts PR, Black KW, et al. Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells. Am J Physiol. 1997 Jan;272(1 Pt 2):H462-8.
83. Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6.