11-19-2013 by Bill Sardi
| PRIMARY GENETIC PATHWAYS TO LONGEVITY | |||
|---|---|---|---|
| Sirtuin1 (activation) | Target of Rapamycin (inhibition) | Nrf2 (activation) to produce internal antioxidants (glutathione, catalase, SOD) |
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| Influenced by |
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BIOLOGICAL STRESSORS
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There are now three genetic longevity pathways being touted. Initially a Harvard professor said longevity is achieved by activation of the Sirtuin1 survival gene. Later another investigator said it is achieved by inhibiting the gene target of Rapamycin with an FDA-approved drug (Sirolimus) generally prescribed to suppress immune system rejection of implanted organs. A third age-reversing gene target is the aforementioned Nrf2 that is targeted by a number of natural molecules and even an FDA-approved drug. Nrf2 is a genetic switch that activates internal antioxidant enzymes (primarily glutathione, catalase, superoxide dismutase).
When I first issued a report that Nrf2 is probably the greatest life force ever discovered, my small audience of readers wondered if I had slipped off the end of a scientific limb. Even pharmaceutical companies now express interest in developing Nrf2 drugs.
For those longevity seekers who are not quite ready to add an advanced garlic pill to their daily health regimens until they learn more, it needs to be pointed out that most of the beneficial effects of a calorie restricted diet emanated from activation of the Nrf2 antioxidant control factor.
Deprenyl, an FDA-approved drug for the treatment of Parkinson’s disease, initially panned as a brain “picker-upper” for senior adults (is metabolized to amphetamine and is a brain stimulant), was found to activate Nrf2 in 2006. There are reports of unusual longevity among Deprenyl users. However, Deprenyl doesn’t activate glutathione, a key antioxidant, as does resveratrol and garlic.
Deprenyl is available with doctor’s prescription and costs about $60 a month. Doctors are not likely to prescribe it for anti-aging purposes.
A main point to grasp is that Deprenyl, rapamycin, resveratrol and allicin in garlic are perceived as mild biological threats in low dose. This is what triggers the body to produce via the Nrf2 gene transcription factor, activation of protective internal antioxidants (glutathione, catalase, heme oxygenase and superoxide dismutase).
Another interesting fact is that an Nrf2 activating dietary supplement is already in widespread use. It is a combination of five herbals and is well documented in the literature. It is sold via a multi-level network and costs $40-50 for a month’s supply. Sales of that product in 2022 exceeded $40 million. That is greater than all 432 brands of resveratrol pills combined.
| Pharmaceutical Nrf2 Activators |
| Rapymycin (Sirolimus) Deprenyl (Eldepryl) |
| Branded Nrf2 Activators: Dietary Supplements |
| Protandim (5 herbs) |
| Unbranded Natural Ingredients That Activate Nrf2 |
| Resveratrol, ginger, garlic, quercetin, many others |
Maybe some longevity seekers will wait for that Harvard professor to announce he has begun taking a garlic pill. Ironically, the Harvard professor who introduced the theory that the red wine molecule resveratrol molecularly mimics a life-prolonging calorie restricted diet first proposed that resveratrol works by virtue of a hormesis effect. Hormesis is defined as a low-dose biological stressor that increases internal body defenses. Nrf2 is an example of hormesis. The Harvard professor’s gene target, the Sirtuin1 survival gene, is known to activate Nrf2 protective antioxidant mechanisms. Calorie restriction also activates Nrf2. All genetic roads to longevity pass through Nrf2.
When the public begins to focus on Nrf2 activators it will find an abundance of them in nature. This will undoubtedly open “Pandora’s Nrf2 box.” Which one, or two, or three Nrf2 activators to use and at what dose?
It is already a foregone conclusion that allicin derived from enzyme activated garlic is the most potent Nrf2 activator at the lowest dose. This is because allicin is very, very pungent. It is the pungency of allicin that activates Nrf2. And it is clearly evidence that allicin does this in microgram doses (2400-2800 micrograms/2-4 milligrams per crushed garlic clove). Garlic is also the least expensive herbal powder.
| Resveratrol | Garlic | |
|---|---|---|
| Molecular size | 228 Daltons | 162 Daltons |
| Pro-oxidant or Antioxidant | Promotes oxidation at high dose; antioxidant at low dose | Allicin: strong oxidant; must be used in small doses as provided in a clove of garlic |
| Dosage range | 100-350 mg Source: J. Nutritional Biochemistry June 2009 |
2-3 mg (2000-3000 mcg) |
| Thins the blood (inhibits platelet clumping) | X Source: Internat’l Journal Molecular Medicine 2002 |
X Source: J. Agric. Food Chem. Nov 2000 Attributed to adenosine in garlic rather than allicin Source: Agents Actions March 1990 Not cooked garlic Source: Prosta. Leuko Essential Fatty Acids Jan 1999 |
| Protects heart (preconditions) heart prior to heart attack | X Source: Canadian J. Physiology Pharmacology Nov. 2022 Superior protection achieved with Longevinex Source: PLos ONE Dec. 2022 |
X Source: Circulation Research Aug. 2009 Freshly crushed garlic (yielding allicin) is superior Source: J. Agric. Food Chem. Aug 2009 |
| Dilates (widens) blood vessels/mechanism | X Nitric oxide |
X Nitric oxide, Hydrogen sulfide |
| Lowers cholesterol | Modest cholesterol reduction. Source: Nutrition Research 2022 Can be used synergistically with statin cholesterol-lowering drugs. Source: J. Nutritional Biochemistry Aug 2022 |
Only when allicin is produced Source: Planta Medica 2001 |
| Strong antibacterial action | X Some antibacterial properties Source: FEMS Micriobiology Letters |
X Allicin (not garlic) exhibits activity against bacteria, viruses, fungus (Candida albicans) and protozoa Source: Microbes Infection 1999 |
| Cancer cell killing | X Only at high dose Source: Molecular Nutrition Food Research Oct 2022 |
X Source: Nutrition & Cancer 2000 |
| Controls copper | X Source: Biochemical Pharmacology May 1997 |
X Source: Planta Medica Aug 2006 |
| Inhibits growth H pylori | X Source: Biol. Pharm. Bulletin Nov 2009 |
X Source: Acta Medica 2001 |
| Controls genes via histone bodies (histone deactylase inhibition) | X Source: Molecular Cell Endocrinology Feb. 2009 |
X Source: Anticancer Agents Med. Chemistry March 2022 |
Crushing a fresh garlic clove may appear to be a more economical and readily available way to produce allicin, but the pungency of chewed and swallowed whole cloves produces considerable distress in the esophagus. Furthermore, a bulb of garlic runs around $3.25/12-16 cloves, which comes to 20-30 cents per clove, about the cost of a Garlinex™ capsule.
While standard garlic powder does protect the heart from damage prior to a heart attack (what is called a preconditioning effect), the protective effect is far superior when fresh crushed cloves, yielding allicin and in particular hydrogen sulfide gas, are used.
Answer: Generally, the medical literature advises caution when consuming garlic products or fresh garlic when taking prescription blood thinners. However, in one study no bleeding episodes were recorded among patients taking warfarin and fresh garlic or garlic supplements.
In another study, garlic pills did not produce bleeding episodes among genetically vulnerable patients taking warfarin.
However, it is possible that some patients taking blood thinning drugs may also take resveratrol, garlic, ginkgo biloba, all which are natural blood thinners. So there is caution in saying garlic will not cause bleeding because of use of multiple drugs and herbal products. – Bill Sardi, November 2022
