Comprehensive Library Of Resveratrol News

Modern medicine is at it again, attempting to develop an expensive synthetic molecule that will reap billions of dollars of sales when there is a more economical natural molecule that may even work in a superior fashion to a heralded new drug.

Here’s the new option now that researchers believe a recent breakthrough can avert age-related mental decline: (1) wait ten years for completed trials of a synthetic drug that abolishes memory loss which commonly occurs with advancing age; or (2) take resveratrol pills that work by a similar if not stronger mechanism than the aforementioned drug.

Of course, waiting ten years and allowing age-related dementia to progress would be folly.  Some people don’t have ten years to wait, and the drug is likely to cost a small fortune.  Users should start to use the drug in middle age when researchers report chronic inflammation takes its toll in the human brain.  But it’s not available, while resveratrol is widely sold as an economical dietary supplement.

Here’s the story:

Researchers believe they have uncovered the foundation of progressive mental decline referred to as dementia.

A newly published study (Science Translational Medicine, Volume 11, Issue 521, 8283) reveals brain cells aren’t dying, but are just disrupted by an “inflammatory fog” that is facilitated by leakiness of the blood-brain barrier (BBB), a barricade that keeps potentially toxic substances from entering the brain.

Leakage of albumin through a leaky BBB is the earliest step in dementia.  This destructive mechanism is also involved with epilepsy.

Once the blood-brain barrier (BBB) is breached, a bloodstream protein known as albumin can enter the brain and target a molecular doorway called the TFG-beta (Transforming Growth Factor-Beta).

Albumin, a viscous protein produced in the liver, volumizes the blood serum by binding to water so fluid doesn’t leak into other tissues.  Albumin also transports various hormones, vitamins and enzymes throughout the body.

Permeability of the aging brain due to breakdown of the blood brain barrier.

Researchers found albumin is absent from the memory-center (hippocampus) of the brain of young animals but is detectable in middle-aged lab animals.  Higher levels of albumin are found in the hippocampus of aged but not young human adults.  This means the BBB begins to break down relatively early in life in both lab animals and humans as albumin slips through the BBB.

It is by BBB breakdown and disruption that heavy metals can enter the brain, metals that are associated with mental decline.

Albumin also binds to the TGF-beta cell receptor (doorway) on the surface of brain cells.

In lab animals whose brain cells are genetically bred NOT to produce TGF-beta signaling, a reversal of symptoms of muscle twitching, cramps, sweating, exercise intolerance, is observed.  So, the TGF-beta pathway is considered paramount in the onset of dementia.

Researchers found targeted inhibition of TGF-beta signaling is sufficient to reverse cognitive (mental) impairment in lab animals.

The synthetic drug

Researchers employed a small synthetic molecule that is only known by its scientific name (IPW-5371).  That drug that targets and inhibits TGF-beta. IPW-5371, when used near the end of the life of lab mice, restored TGF-beta signaling similar to that of younger mice.  Fewer of these treated mice died.  This small drug molecule reduced slow-brain waves.  After just 7 days, the treated old mice exhibited improved mental function.

This same small synthetic drug molecule has also been demonstrated to restore brainwaves in old laboratory mice to a level seen in healthy young animals, which strongly suggests dementia can be prevented, even reversed.

Are aged adults too old to benefit from this discovery?  In the drug-treated mice, memory decline and ability to perform mental tasks improved in old mice when given the experimental drug.  This suggests a reversal and restoration of a youthful brain.

Researchers described this discovery as “astounding.” Older animals completed tasks as if they’d never had dementia,” researchers said.

Modern medicine appears to have been on the wrong track in its attempts to prevent or treat mental decline in old age by inhibition of beta amyloid plaque.  A breakdown of the BBB is increased in dementia but is not related to beta amyloid plaque in the brain.

Enter resveratrol

The red wine molecule resveratrol exhibits a compelling role in blocking the deleterious effects that result from breakdown of the BBB.

There is a symbiotic relationship between albumin and resveratrol.

The binding of resveratrol to human serum albumin is well documented.  Resveratrol has to be bound by human serum albumin to maintain a high concentration in serum, since its solubility is low in water (blood serum).

Albumin protects trans-resveratrol, the active form, from degradation to cis-resveratrol.

Resveratrol binds to albumin in a superior fashion to other small natural molecules such as quercetin, curcumin, genistein and other polyphenols.  This was also confirmed in another study.

Resveratrol binds to albumin in a stronger manner than pterostilbene, a methylated form of resveratrol that is commercially available.

Resveratrol was found to exhibit stronger binding to albumin than a well-known anti-cancer chemotherapy drug.

Resveratrol binds stronger to albumin than hemoglobin in red blood cells.

Resveratrol is metabolized in the liver as part of a detoxification process by its attachment to glucuronate.  Glucuronidated resveratrol binds to human serum albumin as well as unmetabolized resveratrol.

Given that studies show this BBB disruption begins in mid-life, TGF-beta inhibitors like resveratrol may be required to prevent future damage.

• When brain hemorrhages are experimentally produced in young lab animals, transforming growth factor-beta (TGF-beta) increases which then increases brain injury.  When resveratrol was given to the lab animals, brain damage was limited and blood-brain barrier disruption was reduced and animals exhibited improved neurological function.
• Alcohol is known to damage brain cells.  When alcohol is given to lab animals in infancy, immediately after birth when their brain cells are forming connections, extensive damage is produced.  Alcohol-fed animals exhibited memory impairment and behavioral deficits.  Resveratrol treatment significantly reduced this damage via reduction of TGF-beta.
• In the animal lab, an experimental stroke was induced that blocked blood circulation to the brain, and then circulation was restored with accompanying oxygen-induced damage to brain cells.  The experiment was repeated with the animals given resveratrol.  There was less inflammation and disruption of the blood-brain barrier.

Other small natural molecules also bind inhibit TGF-beta.

• Both quercetin and fisetin inhibit TGF-beta.
• Rice bran IP6 (inositol hexaphosphate) inhibits TGF-beta.
• Quercetin and fisetin synergistically inhibit TGF-beta induced inflammation.
• Resveratrol and these other small molecules are uniquely found in a patented formula under the commercial name Longevinex®.

Ideally the objective is to inhibit but not entirely block excessive levels of TGF-beta as it is a key protein that is involved in wound healing.

Vitamin C is another factor that affects the integrity of the blood-brain barrier.  Most animals internally secrete vitamin C from their liver.  Due to a universal gene mutation, humans no longer endogenously synthesize vitamin C which leads to a leaky blood-brain barrier.  Animals that are genetically altered to not produce vitamin C internally exhibit a disrupted BBB.