Lessons from Biology: How can we live long and healthy? --Updated 12/29/08
First off... Happy Thanksgiving! Now... exercise and a good diet are probably the most important factors in health, but...
It's a wonder that only about 55 and 57 years ago DNA/RNA and proteins, as we know them now, were brand new discoveries. In half a century, we've come from knowing nothing about these building blocks of life to sequencing and mapping our own genome and manipulating the DNA of lesser animals from flies to mice. This is a staggeringly short time, a scientific singularity, and as such every year major advances in our understanding of biology are made. Other than exercise and a good diet, let me go into four new "breakthroughs" that have been recently made in regards to the effects of the molecules Methylene Blue, Quercetin, Omega fatty acids, and Resveratrol on metabolism, immunology, cancer and ultimately life span; and how one can use these to increase your health and potentially life.
Methylene Blue
History: Methylene blue is a synthetic molecule that has been in use for over 100 years. It is typically used in industry as a dye for fabrics and DNA staining in biology. It is also used to treat methemoglobinemia disorder[1], urinary track infections[2], and is an antidote to cyanide poisoning[3]. It was, for a time, used successfully to treat malaria in soldiers doing the second world war, but was discontinued due to the soldiers not liking the side effects (blue urine, eye whites, and skin) caused by the high doses needed to kill the malaria parasite[4,5].
Effects: Recently, it has been discovered that much lower doses than the 1-2mg of methylene blue used to treat methemoglobinemia have extraordinary unforeseen beneficial effects. For instance, low doses of methylene blue in the ~100 nanomolar (~30-100 micrograms in a human) range are able to inhibit tau protein fiber formation and stop Alzheimer's disease[6]; increase mitochondrial function, and are capable of reversing mitochondrial dysfunction (the major source of aging), especially through the upregulation of Complex IV and anti-oxidant proteins; increase glycolysis independent of NAD levels (increase metabolism); and increase in vitro cell life span by 40-50%, and whole mouse life span[7]. That is, ~100 nanomolar levels of methylene blue can stop and even reverse cellular senescence responsible for aging and neural degenerative diseases such as Alzheimer's and Parkinson's, keeping neurons and cells youthful and healthy, protect the body from free radicals, and safely increase metabolism.
Availability: Methylene blue is very cheap. It comes relatively pure, with all the chemical analysis of it that I've seen showing heavy metal levels well below acceptable limits. This isn't surprising as methylene blue is used in fish tanks to kill parasites and fungi - but fish are very sensitive to heavy metals. One can find methylene blue at most science novelty shops, Walgreen in the southern part of the US (at least in Florida), pet stores, and on-line. It is a safe chemical, and toxic effects are not seen till around 70mg per kg of body weight per day in a mouse[8]. That is, I'm 63.6 kilograms, but have a metabolic speed about 1/7th a mouse, so, I would have to eat 636 mg of methylene blue in one day to have any sort of the most minor adverse effects - WELL above the minuscule level of ~1000 micrograms (1 mg) per day needed to see its wondrous benefits (that is 600 times less than the lowest adverse dose). The lethal dose 50 (the dose needed to kill half of those who take it) is around 1000mg/kg in mice, or ~9 grams for a person of my weight.
However do NOT get the compound "NEW METHYLENE BLUE". This is a completely different molecule from methylene blue that is quite toxic, and has no beneficial attributes. Real methylene blue has the chemical CAS number 61-73-4. Do not get any version that has any CAS number different from this, or which is not sold in a general pharmaceutical/pet store.
Usage: A 1% (10mg/ml) solution of methylene blue is what I have. Since it is absorbed around 30-50% via ingestion[9,10], 30-100 microliters (300-1000 micrograms) of the 1% solution per day (I mix it with tea to avoid staining of the tongue or lips) is enough to give a concentration range of 100-300 nanomolar of methylene blue in the body assuming 5 liters of blood in the average person. At 100 microliter per day doses, there might be very slight discoloring of urine with a tint of green after waking up showing that this may be about the highest effective range to be taking. Even at these doses, methylene blue can cause stomach aches if taken without any sort of food, and may cause drowsiness (at least in me), and effect which is completely countered and overridden by our next item.
Quercetin
History: They say an "apple a day keeps the doctor away"? The reason for this seems to be quercetin. Quercetin is found at one of its highest natural levels in apples, especially the skin, and is highest in capers. It is a plant derived compound and a member of the bioflavonoid family, and happens to be the most active[11,12,13,14].
Effects: Quercetin has anti-cancer[15,16,17], anti-inflammatory[18], anti-viral[19,20], anti-histamine[21], and anti-oxidant activity[22,23]. It also increases mental concentration/focus and alertness, and physical energy by possibly decreasing the rate at which natural levels of adrenaline are lost from the body[24]. Quercetin increases capillary permeability and increasing the health of tissues, helps maintain artery elasticity and fight atherosclerosis[25,26], protects neurons from hypoxia and drug induced necrosis[27,28, 29, 30, 31], inhibit mast cells and thus prevent plaques from occurring in arteries, and acts as a Vitamin C sparer - keeping Vitamin C from being processed out of the body too rapidly. Its anti-cancer properties come from its ability to induce apoptosis of only cancerous cells[32]. 20-100 micromoles of quercetin is enough to kill, in a dose dependent manner, up to 90% of cancerous cells in one go while leaving all non-cancerous cells healthy and alive[33]. This apparently is done by inhibiting MAPK pathways crucial for cancer propagation, decreasing levels of the protein survivin at the same time as increasing the death proteins caspases[34], and increasing the cancer watch dog protein p53 - thus priming a malignant cell to self destruct by turning off their ability to override apoptosis, and turning back on the sensors that detect if a cell is bad and start the apoptotic pathways. Most likely it's in this same or similar manner, quercetin acts as an anti-viral. Strangely enough, while quercetin inhibits the aspects of the immune system that causes inflammation and self tissue damage, it also paradoxically increases the effectiveness of the immune system against pathogens of all types, making a person less prone to sickness on all fronts. For instance, quercetin is also an anti-bacterial[35,36] It should be noted that quercetin also inhibits one of the major drug metabolic enzyme in the body; therefore, it increases the effective concentration of statin based drugs and this must be kept in mind when taking quercetin.
Finally, quercetin apparently increases bone density[37,38], fights diabetes[39], and fights obesity[40,41].
Availability: Quercetin is cheap and can be found at GNC stores under the anti-oxidant section, and at any "whole foods" or "natural" stores. For instance, I get my quercetin at a store called Wild Oats. There's a lot of gems to be found at such places that aren't part of the usual drudge in a pharmaceutical.
Usage: Quercetin is non-toxic, non-carcinogenic, and not a neurotoxin in vivo at all[42,43,44,45], and it's apparently safe to take even up to 2000 mg per kg body weight per day (though that's way too high). Both its in vitro human neural protective and anti-cancer effects are seen to peak at ranges of 20-100 micromolar, but it shouldn't be taken at doses that'll push its in vivo concentration above 200 micromolar, I feel. There's always the law of diminishing returns, not to mention the inverted U shaped dose response curve - more isn't better once you find the right level.
500 milligrams (mg) per day is what I take. Since its absorption rate by ingestion is 20-50%, 500 mg will give about 0.5-1 micromoles of quercetin in the body with a half life of ~16 hours[46] (1gram per day for 28 days gives about 1.5 micromols in the blood[47]). Quercetin is absorbed very poorly on its own, but is enhanced when taken with fatty acids, which brings us to our next item.
Omega Fatty Acids
History: Omega fatty acids are mono and polyunsaturated fatty acids. That means, there's a double bond "kink" in the long chain of carbons that makes up the "fatty" part of the acid. They are called "omega" as the numbering convention begins with the final carbon (the omega carbon) of the chain and counting the carbons till the first double bond is reached. There are three types of these fatty acids, linolenic acid (Omega-3), linoleic acid (Omega-6), and oleic acid (Omega-9). All three of these fatty acids are produced by plants and fish to a lesser extent - our bodies, and mammals in general, are incapable of making them, as with the other two molecules listed so far.
Effects: How exactly omega fatty acids do what they do is a mystery still, as far as I know. Why they are beneficial is a question of research, but how they are beneficial has been well established. Omega fatty acids help to protect the heart and cardiovascular system from disease, heart attacks, strokes, and atherosclerosis. They also are potent in keeping the brain healthy and functional. These fatty acids most likely do so by inserting into cell membranes to keep the membranes fluid, dynamic, and active - a vital attribute to cell function and whole organ health[48].
Availability: There are two main sources you can find everywhere, including your local grocery store: cod fish oil, and flax seed oil, and both are cheap. Flax seed oil is far more beneficial than cod oil, having a higher concentration of omega fatty acids and much lower concentrations of less beneficial saturated fatty acids, as well as having lignans and other phytochemicals, which also can protect the heart and especially keep arteries elastic.
Usage: The national academy of science recommends taking ~1.2 grams of omega-3 fatty acids per day, however, there is no known upper limit and the flax seed oil I have has about 4 grams.
Resveratrol
History: Here we come to our last breakthrough chemical, and the second most recently discovered, after the new found properties of methylene blue at 100 nanomolar concentrations. Resveratrol (try to say that 10x fast) is a chemical made by grapes and thus commonly found in red wine. It and quercetin are what give low doses of red wine (a glass a day) the beneficial effects that have been seen. Resveratrol is a very interesting molecule.
Effects: From yeasts, to worms and flies, to mice, resveratrol intake can increase life span from 20-40%! (70% life span increase if you're a yeast, 16% at most for mice, so it alone likely doesn't increase maximum human lifespan)[49,50,51,52] Moreover, 400 mg per kg per day doses given to mice doubles the physical endurance and (somewhat) strength of said mice[52]! Literally, doubles endurance both for mice on restrictive pure health diets (best diet you can get) and those on extremely poor high fat diets (McDonald's every day). Furthermore, mice on 22 mg/kg resveratrol have significantly lower weight when on a high fat diet, than mice without resveratrol, staying much slimmer and closer to the size of perfect diet mice, even while being less active and having a lower resting heart rate[53]. Resveratrol also fights type 2 diabetes by increasing insulin sensitivity significantly and glucose metabolism[52,54], has some anti-cancer properties like quercetin[55,56], and is somewhat anti-inflammatory[57] and protective against radiation[58,59]. Mice on resveratrol do not experience many of the adverse effects of a high fat diet, and also resveratrol abrogates most adverse effects of aging it seems. That is, even though maximal life spans may or may not go up, these mice and yeast and worms and flies stay much healthier up to the day they die, and do not experience many of the conditions associated with aging[52]. It is, sufficient to say, amazing. Bone density is significantly increased[50] (prevents osteoporosis) and joints are protected[60,61,62] along with vitamin D receptor upregulation[63,64], arteries stay healthy[65], metabolic dysfunction is not seen, and genetic markers stay similar to healthy young individuals[52,65,66].
Finally, resveratrol also protects neurons[67,68,69], fights Alzheimer's[70,71,72,73], Parkinson's[74,75], multiple sclerosis[76,77], ALS[73,78], epilepsy[79,80,81,82], and potentially numerous other neurological disorders[73].
Resveratrol does this not only by some direct chemical effect as we've seen with the last three, but by increasing the activity of sirtuins[52]. These proteins are master regulators that keep the gene expression profile of a cell in check. They also act as DNA repair enzymes, being first responders to sites of damage to begin the repair process. Since every cell in our bodies have the entire genome, that is, every cell is completely identical genetically, differences between a neural cell and a heart cell are due fully and only to the patterns of gene expression, which are maintained and overseen by sirtuins. When one ages, sirtuins begin to get overwhelmed by DNA damage that accumulates as mitochondria begin to become dysfunctional and reactive oxygen species production increases. As sirtuin levels are pulled away for damage repair, genes that were silenced begin to come on[83]. That is, a heart cell might start expressing liver cell genes, and as soon as that happens, badness begins and the effects of aging begin to be seen. Sirtuins can reverse this leakage of supposed to be silenced genes if given the chance. There's where resveratrol comes in, upregulating sirtuin genes and reversing the effects of aging and high fat diets[52,84].
Availability: I've found this product at the same whole foods store as quercetin. However, it's usually paired, and in low levels of trans-resveratrol, with other grape extracts, so the type I'm taking only has 14mg of trans-resveratrol (equivalent to 1 liter of good red wine, but still very, very low). However, myrevgenetics.com has an amazing combination of 250 mg of resveratrol mixed with tween-80 to give incredibly better absorption, equivalent to 1-3 grams of resveratrol by itself. Now that's the way to go, and I'll use that once I have the money, one day.
Usage: This is the interesting part. Remember the super mice with double endurance and much greater strength, yet lower heart rate, weight, and activity needs? Looking back up, we see those mice were ingesting 400 mg/kg/day of resveratrol. This equates, for me, a daily intake of about 3600 mg, again since humans have a slower metabolism. However, since 22 mg/kg/day in mice is all that's necessary for the rest of its good effects, I'd need only ~200-500 mg per day, not bad at all. Also, the mice taking 400 mg/kg/day had constant serum levels of around 100 micromolar. For a human with 5 liters of blood, that requires consuming ~500 mg with only a ~20% absorption rate[85], or ~1 gram with 1% absorption rate, but also depends on how long resveratrol remains unprocessed in the system. Resveratrol doesn't seem to have any adverse side effects, for instance, mouse behavior is identical between those on 400 mg/kg of it and those not, aside from the super power of those on it, and no lifespan decrease was seen at an insane dose of 2400 mg/kg[50]. What the actual lowest limit is to have the effects of resveratrol be apparent, I'm not sure, but again, 500 mg isn't hard to come by and on-line there are 500-1000 mg capsules being sold, and the myrevgenetics.com site has by far the most economical and best solution I've seen. I'm still reading many scientific papers to figure out the lowest limit. However, since red wine, which has only around 14 mg of resveratrol per liter, has significant benefits, doses even 1/100 of the small amount given here may be enough for some benefit if paired with quercetin, which is also in red wine. This is because quercetin increases the span that resveratrol lasts in the system by inhibiting its degradation, thus increasing its effective concentration[86,87], not to mention how well the two pair synergistically. Also to note is that trans-resveratrol is the most active form, cis-resveratrol does next to nothing, so always factor that out of total resveratrol concentrations to find the useful amount.
There you have it, four super chemicals that may change the face of medicine, and lead to substantially longer and healthier lives. In summary:
Methylene blue - ~300-1000 micrograms (30-100 microliters of 1% solution, so you'll need a syringe or dropper (1 drop is ~50 microliters), or to dilute it more) daily, giving about 100-300 nanomoles in the body, may stop Alzheimer's and Parkinson's, increase life span, stop mitochondrial dysfunction and cellular aging, and reverse cellular senescence.
Quercetin - 500-1000 mg (40 mg in one apple if with skin) daily acts to kill cancer while leaving healthy tissue healthy; kill viruses; enhance the power of the immune system, while acting as an anti-inflammatory/anti-histamine to stop self damage; enhance physical energy and endurance, metal concentration and focus; increase heart and vascular health; protect neurons and cells from necrosis; and act as an anti-oxidant to prevent damage associated with aging.
Omega Fatty Acids - From flax seed oil, 1.2-4 grams daily greatly increases heart, vascular, and brain healthy to reduce heart disease/attacks, hardening of the arteries, and strokes. May have even more beneficial roles.
Resveratrol - 500-3600 mg daily (can be bought anywhere from 500-1000 mg capsules, or 250 mg with tween-80 which is super effectively absorbed, otherwise 500-1000 mg per day is probably enough when paired with quercetin), also found in red grapes/wine. Very powerful anti-aging compound and protector from associated ill effects, as well as metabolism enhancer and protector from the ill effects of a high fat diet (in mouse studies it grants the same health as if on a perfect diet). Increases physical power by double at highest listed dose, in mice, but a person should stay around 200-500 mg with quercetin. Some anti-cancer and radiation protective effects, bone and joint protection, heart and vascular protection, and neurological protection.
All of these except methylene blue are available over the counter at pharmacies and "natural/whole" food stores. Methylene blue is available over the counter at science/hobby stores, and some pharmacies in certain places (Walgreen's in Florida).
Note, this is a rough guide, and anything one ingests they do so at their own risk :P. But I'm taking the first three at the levels recommended here already, and have experienced marked benefits - especially from quercetin which has greatly increased my daily energy level, in that I don't feel nearly as tired as I always did before. Methylene blue and omega-3s are more passive, the effects they give you can't be seen till later in life by you not getting sick and suffering horrible effects of aging and associated diseases like Alzheimer's and heart disease. Although, methylene blue and omega fatty acid effects also can manifest in better skin health/glow and faster nail growth, all signs of happy cells. Resveratrol is also mostly passive if one is already healthy, however it does increase cold resistance I've discovered, quite well too!
I also don't take anything on the weekend, giving my body time to detox and reset to normal - which may or may not be important, who knows; but I feel it's quite important, to avoid desensitization and any unknown chronic effects, and I tend to think our natural levels are important to keep around, in a holistic sense.
Ah science.. who knows what we'll find next - but considering these compound (aside from methylene blue, which was a total shock) all come from natural sources that were known to give remarkable health benefits (apple a day...), I guess it is one of those "about time" sort of things, haha; dunno how many more may be out there, if any other major ones like these four.
It's a wonder that only about 55 and 57 years ago DNA/RNA and proteins, as we know them now, were brand new discoveries. In half a century, we've come from knowing nothing about these building blocks of life to sequencing and mapping our own genome and manipulating the DNA of lesser animals from flies to mice. This is a staggeringly short time, a scientific singularity, and as such every year major advances in our understanding of biology are made. Other than exercise and a good diet, let me go into four new "breakthroughs" that have been recently made in regards to the effects of the molecules Methylene Blue, Quercetin, Omega fatty acids, and Resveratrol on metabolism, immunology, cancer and ultimately life span; and how one can use these to increase your health and potentially life.
Methylene Blue
History: Methylene blue is a synthetic molecule that has been in use for over 100 years. It is typically used in industry as a dye for fabrics and DNA staining in biology. It is also used to treat methemoglobinemia disorder[1], urinary track infections[2], and is an antidote to cyanide poisoning[3]. It was, for a time, used successfully to treat malaria in soldiers doing the second world war, but was discontinued due to the soldiers not liking the side effects (blue urine, eye whites, and skin) caused by the high doses needed to kill the malaria parasite[4,5].
Effects: Recently, it has been discovered that much lower doses than the 1-2mg of methylene blue used to treat methemoglobinemia have extraordinary unforeseen beneficial effects. For instance, low doses of methylene blue in the ~100 nanomolar (~30-100 micrograms in a human) range are able to inhibit tau protein fiber formation and stop Alzheimer's disease[6]; increase mitochondrial function, and are capable of reversing mitochondrial dysfunction (the major source of aging), especially through the upregulation of Complex IV and anti-oxidant proteins; increase glycolysis independent of NAD levels (increase metabolism); and increase in vitro cell life span by 40-50%, and whole mouse life span[7]. That is, ~100 nanomolar levels of methylene blue can stop and even reverse cellular senescence responsible for aging and neural degenerative diseases such as Alzheimer's and Parkinson's, keeping neurons and cells youthful and healthy, protect the body from free radicals, and safely increase metabolism.
Availability: Methylene blue is very cheap. It comes relatively pure, with all the chemical analysis of it that I've seen showing heavy metal levels well below acceptable limits. This isn't surprising as methylene blue is used in fish tanks to kill parasites and fungi - but fish are very sensitive to heavy metals. One can find methylene blue at most science novelty shops, Walgreen in the southern part of the US (at least in Florida), pet stores, and on-line. It is a safe chemical, and toxic effects are not seen till around 70mg per kg of body weight per day in a mouse[8]. That is, I'm 63.6 kilograms, but have a metabolic speed about 1/7th a mouse, so, I would have to eat 636 mg of methylene blue in one day to have any sort of the most minor adverse effects - WELL above the minuscule level of ~1000 micrograms (1 mg) per day needed to see its wondrous benefits (that is 600 times less than the lowest adverse dose). The lethal dose 50 (the dose needed to kill half of those who take it) is around 1000mg/kg in mice, or ~9 grams for a person of my weight.
However do NOT get the compound "NEW METHYLENE BLUE". This is a completely different molecule from methylene blue that is quite toxic, and has no beneficial attributes. Real methylene blue has the chemical CAS number 61-73-4. Do not get any version that has any CAS number different from this, or which is not sold in a general pharmaceutical/pet store.
Usage: A 1% (10mg/ml) solution of methylene blue is what I have. Since it is absorbed around 30-50% via ingestion[9,10], 30-100 microliters (300-1000 micrograms) of the 1% solution per day (I mix it with tea to avoid staining of the tongue or lips) is enough to give a concentration range of 100-300 nanomolar of methylene blue in the body assuming 5 liters of blood in the average person. At 100 microliter per day doses, there might be very slight discoloring of urine with a tint of green after waking up showing that this may be about the highest effective range to be taking. Even at these doses, methylene blue can cause stomach aches if taken without any sort of food, and may cause drowsiness (at least in me), and effect which is completely countered and overridden by our next item.
Quercetin
History: They say an "apple a day keeps the doctor away"? The reason for this seems to be quercetin. Quercetin is found at one of its highest natural levels in apples, especially the skin, and is highest in capers. It is a plant derived compound and a member of the bioflavonoid family, and happens to be the most active[11,12,13,14].
Effects: Quercetin has anti-cancer[15,16,17], anti-inflammatory[18], anti-viral[19,20], anti-histamine[21], and anti-oxidant activity[22,23]. It also increases mental concentration/focus and alertness, and physical energy by possibly decreasing the rate at which natural levels of adrenaline are lost from the body[24]. Quercetin increases capillary permeability and increasing the health of tissues, helps maintain artery elasticity and fight atherosclerosis[25,26], protects neurons from hypoxia and drug induced necrosis[27,28, 29, 30, 31], inhibit mast cells and thus prevent plaques from occurring in arteries, and acts as a Vitamin C sparer - keeping Vitamin C from being processed out of the body too rapidly. Its anti-cancer properties come from its ability to induce apoptosis of only cancerous cells[32]. 20-100 micromoles of quercetin is enough to kill, in a dose dependent manner, up to 90% of cancerous cells in one go while leaving all non-cancerous cells healthy and alive[33]. This apparently is done by inhibiting MAPK pathways crucial for cancer propagation, decreasing levels of the protein survivin at the same time as increasing the death proteins caspases[34], and increasing the cancer watch dog protein p53 - thus priming a malignant cell to self destruct by turning off their ability to override apoptosis, and turning back on the sensors that detect if a cell is bad and start the apoptotic pathways. Most likely it's in this same or similar manner, quercetin acts as an anti-viral. Strangely enough, while quercetin inhibits the aspects of the immune system that causes inflammation and self tissue damage, it also paradoxically increases the effectiveness of the immune system against pathogens of all types, making a person less prone to sickness on all fronts. For instance, quercetin is also an anti-bacterial[35,36] It should be noted that quercetin also inhibits one of the major drug metabolic enzyme in the body; therefore, it increases the effective concentration of statin based drugs and this must be kept in mind when taking quercetin.
Finally, quercetin apparently increases bone density[37,38], fights diabetes[39], and fights obesity[40,41].
Availability: Quercetin is cheap and can be found at GNC stores under the anti-oxidant section, and at any "whole foods" or "natural" stores. For instance, I get my quercetin at a store called Wild Oats. There's a lot of gems to be found at such places that aren't part of the usual drudge in a pharmaceutical.
Usage: Quercetin is non-toxic, non-carcinogenic, and not a neurotoxin in vivo at all[42,43,44,45], and it's apparently safe to take even up to 2000 mg per kg body weight per day (though that's way too high). Both its in vitro human neural protective and anti-cancer effects are seen to peak at ranges of 20-100 micromolar, but it shouldn't be taken at doses that'll push its in vivo concentration above 200 micromolar, I feel. There's always the law of diminishing returns, not to mention the inverted U shaped dose response curve - more isn't better once you find the right level.
500 milligrams (mg) per day is what I take. Since its absorption rate by ingestion is 20-50%, 500 mg will give about 0.5-1 micromoles of quercetin in the body with a half life of ~16 hours[46] (1gram per day for 28 days gives about 1.5 micromols in the blood[47]). Quercetin is absorbed very poorly on its own, but is enhanced when taken with fatty acids, which brings us to our next item.
Omega Fatty Acids
History: Omega fatty acids are mono and polyunsaturated fatty acids. That means, there's a double bond "kink" in the long chain of carbons that makes up the "fatty" part of the acid. They are called "omega" as the numbering convention begins with the final carbon (the omega carbon) of the chain and counting the carbons till the first double bond is reached. There are three types of these fatty acids, linolenic acid (Omega-3), linoleic acid (Omega-6), and oleic acid (Omega-9). All three of these fatty acids are produced by plants and fish to a lesser extent - our bodies, and mammals in general, are incapable of making them, as with the other two molecules listed so far.
Effects: How exactly omega fatty acids do what they do is a mystery still, as far as I know. Why they are beneficial is a question of research, but how they are beneficial has been well established. Omega fatty acids help to protect the heart and cardiovascular system from disease, heart attacks, strokes, and atherosclerosis. They also are potent in keeping the brain healthy and functional. These fatty acids most likely do so by inserting into cell membranes to keep the membranes fluid, dynamic, and active - a vital attribute to cell function and whole organ health[48].
Availability: There are two main sources you can find everywhere, including your local grocery store: cod fish oil, and flax seed oil, and both are cheap. Flax seed oil is far more beneficial than cod oil, having a higher concentration of omega fatty acids and much lower concentrations of less beneficial saturated fatty acids, as well as having lignans and other phytochemicals, which also can protect the heart and especially keep arteries elastic.
Usage: The national academy of science recommends taking ~1.2 grams of omega-3 fatty acids per day, however, there is no known upper limit and the flax seed oil I have has about 4 grams.
Resveratrol
History: Here we come to our last breakthrough chemical, and the second most recently discovered, after the new found properties of methylene blue at 100 nanomolar concentrations. Resveratrol (try to say that 10x fast) is a chemical made by grapes and thus commonly found in red wine. It and quercetin are what give low doses of red wine (a glass a day) the beneficial effects that have been seen. Resveratrol is a very interesting molecule.
Effects: From yeasts, to worms and flies, to mice, resveratrol intake can increase life span from 20-40%! (70% life span increase if you're a yeast, 16% at most for mice, so it alone likely doesn't increase maximum human lifespan)[49,50,51,52] Moreover, 400 mg per kg per day doses given to mice doubles the physical endurance and (somewhat) strength of said mice[52]! Literally, doubles endurance both for mice on restrictive pure health diets (best diet you can get) and those on extremely poor high fat diets (McDonald's every day). Furthermore, mice on 22 mg/kg resveratrol have significantly lower weight when on a high fat diet, than mice without resveratrol, staying much slimmer and closer to the size of perfect diet mice, even while being less active and having a lower resting heart rate[53]. Resveratrol also fights type 2 diabetes by increasing insulin sensitivity significantly and glucose metabolism[52,54], has some anti-cancer properties like quercetin[55,56], and is somewhat anti-inflammatory[57] and protective against radiation[58,59]. Mice on resveratrol do not experience many of the adverse effects of a high fat diet, and also resveratrol abrogates most adverse effects of aging it seems. That is, even though maximal life spans may or may not go up, these mice and yeast and worms and flies stay much healthier up to the day they die, and do not experience many of the conditions associated with aging[52]. It is, sufficient to say, amazing. Bone density is significantly increased[50] (prevents osteoporosis) and joints are protected[60,61,62] along with vitamin D receptor upregulation[63,64], arteries stay healthy[65], metabolic dysfunction is not seen, and genetic markers stay similar to healthy young individuals[52,65,66].
Finally, resveratrol also protects neurons[67,68,69], fights Alzheimer's[70,71,72,73], Parkinson's[74,75], multiple sclerosis[76,77], ALS[73,78], epilepsy[79,80,81,82], and potentially numerous other neurological disorders[73].
Resveratrol does this not only by some direct chemical effect as we've seen with the last three, but by increasing the activity of sirtuins[52]. These proteins are master regulators that keep the gene expression profile of a cell in check. They also act as DNA repair enzymes, being first responders to sites of damage to begin the repair process. Since every cell in our bodies have the entire genome, that is, every cell is completely identical genetically, differences between a neural cell and a heart cell are due fully and only to the patterns of gene expression, which are maintained and overseen by sirtuins. When one ages, sirtuins begin to get overwhelmed by DNA damage that accumulates as mitochondria begin to become dysfunctional and reactive oxygen species production increases. As sirtuin levels are pulled away for damage repair, genes that were silenced begin to come on[83]. That is, a heart cell might start expressing liver cell genes, and as soon as that happens, badness begins and the effects of aging begin to be seen. Sirtuins can reverse this leakage of supposed to be silenced genes if given the chance. There's where resveratrol comes in, upregulating sirtuin genes and reversing the effects of aging and high fat diets[52,84].
Availability: I've found this product at the same whole foods store as quercetin. However, it's usually paired, and in low levels of trans-resveratrol, with other grape extracts, so the type I'm taking only has 14mg of trans-resveratrol (equivalent to 1 liter of good red wine, but still very, very low). However, myrevgenetics.com has an amazing combination of 250 mg of resveratrol mixed with tween-80 to give incredibly better absorption, equivalent to 1-3 grams of resveratrol by itself. Now that's the way to go, and I'll use that once I have the money, one day.
Usage: This is the interesting part. Remember the super mice with double endurance and much greater strength, yet lower heart rate, weight, and activity needs? Looking back up, we see those mice were ingesting 400 mg/kg/day of resveratrol. This equates, for me, a daily intake of about 3600 mg, again since humans have a slower metabolism. However, since 22 mg/kg/day in mice is all that's necessary for the rest of its good effects, I'd need only ~200-500 mg per day, not bad at all. Also, the mice taking 400 mg/kg/day had constant serum levels of around 100 micromolar. For a human with 5 liters of blood, that requires consuming ~500 mg with only a ~20% absorption rate[85], or ~1 gram with 1% absorption rate, but also depends on how long resveratrol remains unprocessed in the system. Resveratrol doesn't seem to have any adverse side effects, for instance, mouse behavior is identical between those on 400 mg/kg of it and those not, aside from the super power of those on it, and no lifespan decrease was seen at an insane dose of 2400 mg/kg[50]. What the actual lowest limit is to have the effects of resveratrol be apparent, I'm not sure, but again, 500 mg isn't hard to come by and on-line there are 500-1000 mg capsules being sold, and the myrevgenetics.com site has by far the most economical and best solution I've seen. I'm still reading many scientific papers to figure out the lowest limit. However, since red wine, which has only around 14 mg of resveratrol per liter, has significant benefits, doses even 1/100 of the small amount given here may be enough for some benefit if paired with quercetin, which is also in red wine. This is because quercetin increases the span that resveratrol lasts in the system by inhibiting its degradation, thus increasing its effective concentration[86,87], not to mention how well the two pair synergistically. Also to note is that trans-resveratrol is the most active form, cis-resveratrol does next to nothing, so always factor that out of total resveratrol concentrations to find the useful amount.
There you have it, four super chemicals that may change the face of medicine, and lead to substantially longer and healthier lives. In summary:
Methylene blue - ~300-1000 micrograms (30-100 microliters of 1% solution, so you'll need a syringe or dropper (1 drop is ~50 microliters), or to dilute it more) daily, giving about 100-300 nanomoles in the body, may stop Alzheimer's and Parkinson's, increase life span, stop mitochondrial dysfunction and cellular aging, and reverse cellular senescence.
Quercetin - 500-1000 mg (40 mg in one apple if with skin) daily acts to kill cancer while leaving healthy tissue healthy; kill viruses; enhance the power of the immune system, while acting as an anti-inflammatory/anti-histamine to stop self damage; enhance physical energy and endurance, metal concentration and focus; increase heart and vascular health; protect neurons and cells from necrosis; and act as an anti-oxidant to prevent damage associated with aging.
Omega Fatty Acids - From flax seed oil, 1.2-4 grams daily greatly increases heart, vascular, and brain healthy to reduce heart disease/attacks, hardening of the arteries, and strokes. May have even more beneficial roles.
Resveratrol - 500-3600 mg daily (can be bought anywhere from 500-1000 mg capsules, or 250 mg with tween-80 which is super effectively absorbed, otherwise 500-1000 mg per day is probably enough when paired with quercetin), also found in red grapes/wine. Very powerful anti-aging compound and protector from associated ill effects, as well as metabolism enhancer and protector from the ill effects of a high fat diet (in mouse studies it grants the same health as if on a perfect diet). Increases physical power by double at highest listed dose, in mice, but a person should stay around 200-500 mg with quercetin. Some anti-cancer and radiation protective effects, bone and joint protection, heart and vascular protection, and neurological protection.
All of these except methylene blue are available over the counter at pharmacies and "natural/whole" food stores. Methylene blue is available over the counter at science/hobby stores, and some pharmacies in certain places (Walgreen's in Florida).
Note, this is a rough guide, and anything one ingests they do so at their own risk :P. But I'm taking the first three at the levels recommended here already, and have experienced marked benefits - especially from quercetin which has greatly increased my daily energy level, in that I don't feel nearly as tired as I always did before. Methylene blue and omega-3s are more passive, the effects they give you can't be seen till later in life by you not getting sick and suffering horrible effects of aging and associated diseases like Alzheimer's and heart disease. Although, methylene blue and omega fatty acid effects also can manifest in better skin health/glow and faster nail growth, all signs of happy cells. Resveratrol is also mostly passive if one is already healthy, however it does increase cold resistance I've discovered, quite well too!
I also don't take anything on the weekend, giving my body time to detox and reset to normal - which may or may not be important, who knows; but I feel it's quite important, to avoid desensitization and any unknown chronic effects, and I tend to think our natural levels are important to keep around, in a holistic sense.
Ah science.. who knows what we'll find next - but considering these compound (aside from methylene blue, which was a total shock) all come from natural sources that were known to give remarkable health benefits (apple a day...), I guess it is one of those "about time" sort of things, haha; dunno how many more may be out there, if any other major ones like these four.