Derived Human Dosing of Mouse Enhancement Supplement
In a series of 10 clinical studies, scientists at McMaster University have repeatedly demonstrated that a multi-ingredient dietary supplement can dramatically enhance the cognition and longevity of mice. I contacted one of the scientists, Jennifer Lemon, to ask if and when they plan to proceed with human studies. She assured me that they're preparing to do that soon. I look forward to the results. But wouldn't it be nice if we knew, today, what an equivalent complex nutraceutical supplement for humans might consist of? Well, you're in luck. I have that information for you.
Before I share the formula, note that humans are not mice. What works in mice doesn't always work in humans (and sometimes hurts humans). However, in this case, the formula consists mainly of well-known nutrients that other scientists have independently tested in multiple (generally many) human studies. And those studies have demonstrated that at least some of those nutrients, on their own, can provide significant nootropic and geroprotective benefits to humans. So it wouldn't surprise me if scientists end up demonstrating reliable additive or multiplicative benefits from this combination of nutrients in human studies. But of course the question remains open. Science is never finished.
With that in mind, I'll share with you the formula. It's an approximation, which I have derived from the published mouse doses, converted to human doses. After sharing the formula, I'll share my thoughts on the efficacy of the derived human doses for the individual ingredients. Here's the formula:
|Nutrient||Mouse Dose||Human Dose|
|Acetyl L Carnitine||14.4000000||1000.000|
|Alpha Lipoic Acid||0.7200000||50.000|
|Cod Liver Oil||5.04 IU||?|
|Flax Seed Oil||21.6000000||1500.000|
|Green Tea Extracts||7.2000000||500.000|
|N Acetyl Cysteine||7.2000000||500.000|
|Vitamin A (Beta Carotene)||0.0300000||2.083|
|The information in the "Nutrient" and "Mouse Dose" columns is from studies published by scientists at McMaster University. The information in the "Human Dose" column is generally calculated by multiplying the mouse dose by 69.44445. Unless otherwise specified, doses are in mg.|
Acetyl L Carnitine is in my list of top tier nootropics. It is well researched and may provide neuroprotective benefits. In this formula, the derived human dose of 1000 mg falls in the middle of the range of doses that other scientists have used in human studies of this nutrient. I supplement with 500 to 2000 mg of Acetyl L Carnitine daily.
Alpha Lipoic Acid is well researched in relation to supporting healthy nerve function. And some studies have shown that it may complement the neuroprotective benefits of Acetyl L Carnitine. The derived human dose in this formula is lower than the dose that other scientists generally use in human studies of this nutrient. I would increase the dose to at least 150 mg. Judging from the most common doses in clinical studies, I would also aim for a 3:10 ratio between Alpha Lipoic Acid and Acetyl L Carnitine, which would mean increasing the Alpha Lipoic Acid dose to 300 mg or lowering the Acetyl L Carnitine dose to 500 mg.
Aspirin has become somewhat controversial as a supplement. The latest advice from the American Heart Association is to avoid daily Aspirin unless your doctor prescribes it. The dose in this formula probably falls within the range that doctors tend to prescribe for daily use. I don't supplement with Aspirin, but I would probably start at a lower dose of around 80 mg if I were to try incorporating it into my supplementation regimen.
Bioflavonoids are plant-derived compounds. Some are far better researched than others. I didn't find information about the specific identity of these Bioflavonoids, so it's hard to assess the safety or efficacy of the 300 mg dose in the derived human formula. The formula contains other sources of Bioflavonoids, such as Garlic, Ginger, Ginkgo Biloba, and Ginseng, as well as other Bioflavonoids, such as Green Tea Extracts and Rutin. My lists of top tier nootropics and geroprotectors include several Bioflavonoids and sources of Bioflavonoids, such as Boswellia Serrata (AKBA), Garlic (Allicin), Blueberry (Anthocyanin), Bacopa Monnieri (Bacoside), Berberine, Turmeric (Curcumin), Ginkgo Biloba (Glycoside), French Maritime Pine (Procyanidin), and Rhodiola Rosea (Salidroside).
Chromium is an essential mineral. The derived human dose of .1 mg is above the .035 mg daily value set by the FDA but well below the 1 mg upper limit specified by CRN. The mouse studies used a chelated form of Chromium to improve bioavailability. I try to get Chromium from a healthy diet. It may also be worth considering a high quality multi-mineral supplement containing a chelated form of Chromium.
Cod Liver Oil provides Omega 3, Vitamin A, and Vitamin D, which are also provided by other ingredients in the formula. The studies specified the amount of Cod Liver Oil in IU, which may be a measure of one or both of the vitamins. I'm not sure. I supplement with 500 to 2000 mg Omega 3 and .05 mg Vitamin D daily. I try to get a sufficient dose of Vitamin A from a healthy diet. If you try to get Vitamin A from a supplement, be careful about the dose. I don't know of a good reason for most people to take more than the .9 mg DV set by the FDA.
Coenzyme Q10 is in my list of top tier geroprotectors. It is well researched and may support healthy cell function. In this formula, the derived human dose of 30 mg is lower than the dose that other scientists generally use in clinical studies. I supplement with 100 to 400 mg daily.
DHEA is in my list of top tier geroprotectors. It is well researched and may help the body produce more testosterone or estrogen, as needed. The derived human dose of 10 mg in this formula is on the low end, which I think is wise. My own experiences with and observations of DHEA supplementation suggest that individual results vary more than with most other supplements.
Flax Seed Oil provides Omega 3, which is in both of my lists of top tier nootropics and geroprotectors. It may enhance mood and support healthy triglyceride levels. The derived human dose of 1500 mg in this formula is in the middle of the range of doses used by other scientists in clinical studies. I supplement with 500 to 2000 mg Omega 3 daily.
Garlic is in my list of top tier geroprotectors, for supporting healthy cholesterol levels. However, I don't know of any evidence to support the efficacy of the derived human dose of 1.5 mg in this formula. Most scientists use far higher doses in clinical studies. I supplement with 300 to 1200 mg daily.
Ginger is well studied and effective for decreasing nausea. It's also reasonably well studied in other areas, but apparently with less efficacy than alternatives. The derived human dose of 500 mg may be on the low end. I would consider replacing Ginger with Turmeric.
Ginkgo Biloba is in my list of top tier nootropics. It is well-researched, and may be particularly effective for long term brain health. The derived human dose of 100 mg is on the low end of the range used in clinical studies. I supplement with 100 to 400 mg daily.
Ginseng is well researched, and may provide minor nootropic and geroprotective benefits. Its nootropic benefits may decrease with chronic use. The derived human dose of 600 mg may be toward the high end, but that also depends on the ginsenoside content of the extract. I supplement with Ginseng only occasionally, in combination with Caffeine.
Green Tea Extracts are well-researched and may provide minor geroprotective benefits throughout the body. They have also raised some popular concern recently, due to apparent overdoses. The derived human dose of 500 mg corresponds with doses used by other scientists in clinical studies.
L Glutathione doesn't seem to be as well researched or as effective as alternatives, such as N Acetyl Cysteine, which is also included in the formula. I would consider replacing L Glutathione with N Acetyl Cysteine.
Magnesium is in my list of top tier geroprotectors. It is an essential mineral. The derived human dose of 50 mg is low. The daily value set by the FDA is 420 mg. I try to get half of this from a healthy diet. And I supplement with 200 mg daily.
Melatonin is in my list of top tier nootropics. It's well known for helping people fall asleep more easily. And there's increasing evidence that it may serve as a powerful general-purpose geroprotector. The derived human dose of .694 mg in this formula is within the range used in other clinical studies. However, the geroprotective benefits of melatonin may improve with higher doses, and adverse effects of higher doses are rare. I supplement with 5 mg daily.
N Acetyl Cysteine is well studied and provides antioxidant effects throughout the body. As mentioned above, supplementation with N Acetyl Cysteine appears to increase Glutathione in the body better than Glutathione supplementation. The derived human dose of 500 mg is on the low end of the range used in other clinical studies. I supplement with 600 mg daily.
Potassium is an essential mineral. The derived human dose of 25 mg is above the 4.7 mg daily value set by the FDA, but well below the 1500 mg upper limit specified by CRN. I try to get Potassium from a healthy diet. It may also be worth considering a high quality multi-mineral supplement.
Rutin is a Bioflavonoid. I'm not particularly familiar with the research behind it, but my initial impressions are positive. I'm particularly interested by its relationship to Quercetin, which is a Bioflavonoid that has been prominent in news related to geroprotectors recently. The derived human dose of 50 mg in this formula appears to be substantially lower than the dose provided by most supplements.
Selenium is an essential mineral. The derived human dose of .075 mg is above the .055 mg daily value set by the FDA, but well below the .2 mg upper limit specified by CRN. I try to get Selenium from a healthy diet. It may also be worth considering a high quality multi-mineral supplement.
Vitamin A is an essential vitamin. The derived human dose of 2 mg is well above the .9 mg daily value set by the FDA. This formula uses Vitamin A in the Beta Carotene form, for which CRN specifies an upper limit of 25 mg. I'm not aware of any reasons for healthy adults to supplement Vitamin A, in any form, above the daily value set by FDA. I try to get Vitamin A from a healthy diet. And I would consider replacing this part of the formula with other carotenoids, particularly Lutein and Zeaxanthin, which are well studied and generally effective for enhancing vision.
Vitamin B is a set of essential vitamins. This formula includes Vitamins B1, B3, B6, B9, and B12, which are six of the eight B Vitamins. It does not include Vitamins B2, B5, and B7. All of the B vitamins are well researched. But the particular forms of the vitamins (the vitamers) can make a big difference in bioavailability. And the best evidence for health benefits appears to be associated with taking all of the B vitamins, and mostly at high safe doses. The derived human doses in this formula are hard to judge because I didn't find information about the vitamers. I supplement with 25 mg B1 as Sulbutiamine, 25 mg B2 as Riboflavin 5 Phosphate, 100 mg B3 as Nicotinamide, 100 mg B5 as D Calcium Pantothenate, 25 mg B6 as Pyridoxal 5 Phosphate, .3 mg B7 as D Biotin, .4 mg B9 as Methylfolate, and .24 mg B12 as Methylcobalamin and Adenosylcobalamin daily.
Vitamin C is an essential vitamin. The derived human dose of 250 mg is above the 90 mg daily value set by the FDA, but well below the 2000 mg upper limit specified by CRN. I try to get my Vitamin C from a healthy diet, sometimes accompanied by a dedicated Vitamin C supplement.
Vitamin D is an essential vitamin. The derived human dose of .004 mg is well below the .02 mg daily value set by the FDA, and far below the .25 mg upper limit specified by CRN. The benefits of Vitamin D supplementation appear to be increase with safe high doses. I supplement with .05 mg daily.
Vitamin E is an essential vitamin. The derived human dose of 67 mg is well above the 15 mg daily value set by the FDA but far below the 1000 mg upper limit specified by CRN. There's some controversy surrounding Vitamin E supplementation, at present, because some high doses may be associated with increased risk of death. On the other hand, some less-known forms of Vitamin E and their combinations may provide under-researched benefits. I try to get my Vitamin E from a healthy diet, although I'm watching ongoing research with interest.
Zinc is in my list of top tier nootropics. It is well researched, and may be particularly effective for enhancing mood. The derived human dose of 9.7 mg in this formula is slightly below the 11 mg daily value set by the FDA. The mouse studies used a chelated form of Zinc to improve bioavailability. I supplement with 11 mg of chelated Zinc Picolinate daily.
On the whole, I think this formula has promise. There are a few things I would change, both in mouse studies and human studies. I mention some of those recommended changes above. I would also consider including Vitamin K (particularly Vitamin K2 MK7), a bioavailable source of Choline such as Alpha GPC, Phosphatidylserine, and S Adenosyl Methionine. But, regardless of these recommendations, I look forward to the results of the human studies with the ingredients in this formula.
Thrivous customers will be interested in knowing how this formula (the "Derived Formula" from the McMaster University mouse studies) compares with the formula for Thrivous Stack. And I've spent time reviewing how the Derived Formula compares to my own regimen, which includes Thrivous Stack. So below is a comparison of the nutrients and doses in these formulas. For simplicity's sake, I've combined Bioflavonoids that don't appear in both formulas into a single "Other Bioflavonoids" line item. That shouldn't be interpreted to mean that all Bioflavonoids are equally effective, but the differences in efficacy are more complex than a side-by-side comparison could illuminate, so I've chosen to ignore that in the comparison. I've mentioned some of the differences that may matter in my comments above.
|Ingredient||Derived Formula||Thrivous Stack|
|Acetyl L Carnitine||1000.000||500.000|
|Alpha Lipoic Acid||50.000||150.000|
|N Acetyl Cysteine||500.000||0.000|
|S Adenosyl Methionine||0.000||400.000|
|Vitamin A (Beta Carotene)||2.083||0.000|
|Thrivous Stack doses represent a single daily serving of each product in the stack. All doses are in mg.|
In most areas, a single daily serving of Thrivous Stack compares favorably to the Derived Formula. However, there are a three things that Thrivous Stack customers might consider, if they're interested in making their supplementation regimen look more like the Derived Formula:
- Consider two to four servings of Thrivous Alpha Neuroprotector daily. This would provide at least 1000 mg of Acetyl L Carnitine, which is the dose in the Derived Formula. I do this.
- Consider three to four servings of Thrivous Omega Cardioprotector daily. This would provide at least 1500 mg Omega 3, which is the dose in the Derived Formula. I do this.
- Consider supplementing with Aspirin, Chromium, DHEA, L Glutathione, N Acetyl Cysteine, Potassium, Selenium, Vitamin A, Vitamin C, Vitamin D, and Vitamin E. I think L Glutathione is a waste. I'm skeptical about Vitamin A, except to avoid deficiency. I have mixed thoughts about Aspirin, Chromium, Potassium, Selenium, and Vitamin E. I think DHEA depends highly on personal situations. And I favor supplementation daily with N Acetyl Cysteine and Vitamin D, and occasionally with Vitamin C.
Finally, keep in mind that this is not medical advice. Although science helps us make practical generalizations, everyone's personal situation is at least a little different. So please consult your physician before and during use of all dietary supplements. And don't forget that lifestyle matters: diet, exercise, sleep, meditation, relationships, etc. Supplements work best in combination with other wise choices.
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