The most exciting brain discovery over the past several decades is the ability of the brain to regenerate, or create new neurons, a process called neurogenesis. Also important is the discovery, or at least confirmation, of the brain’s neuroplasticity, that is its ability to re-wire itself and work around damaged, dysfunctional if not dead areas induced by stroke, head traumas, infections, calcification, excess alcohol and stress (cortisol), and just wear and tear.

Several nutritional ingredients, some newcomers to the nutra world, show great promise in promoting neurogenesis and neuroplasticity as well as addressing other significant targets for the protection of brain cells and promotion of brain health and performance.

Some of the following supplements have been used with moderate success in latter stages of memory loss, e.g., MCI (mild cognitive impairment), pre-Alzheimer's, and early-stage Alzheimer’s. However, their optimal use is with early intervention in brain (normal or accelerated) decline, and continued use for lifelong maintenance of optimal brain health and performance.

Most importantly, perhaps no one, or even few ingredients can cover the broad spectrum needs of the aging, let alone compromised, brain. Therefore, the ultimate Alzheimer’s risk reduction supplement may be a combination, if not cocktail of several multi-purpose (“pleiotropic”) ingredients addressing the varied needs of the aging brain.

The aging brain’s three primary needs are for:

1. Enhanced blood flow to the brain (increasing supplies of oxygen, glucose & other vital nutrients)
2. Enhanced neurotransmitter support (primarily, acetylcholine)
3. Enhanced support for waning anti- oxidant and inflammatory defenses

New Neuroceutical Approaches


Natural acetylcholinesterase inhibitors (e.g., Huperzine A) address one of the primary causes of normal and accelerated cognitive decline, which is cholinergic dysfunction (a principal target for the majority of Alzheimer’s drugs). Other new supplements addressing this target include citicoline (aka CDP-Choline; cytidine 5’-diphosphocholine) and Alpha GPC (glycerylphosphorylcholine). Another popular contender is phosphatidylserine (PS), which addresses cholinergic dysfunction, as well as other targets (e.g., cortisol, the stress hormone). PS is one of the only two supplements to gain an FDA-qualified brain health claim:

"Very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly.”

The aging brain also suffers from reduced cerebral circulation, choking off hungry cells from vital supplies (e.g., oxygen, glucose and other nutrients). This compromises brain cell health and function, creating a vicious cycle of reduced neuronal (and mitochondrial) metabolism, which increases free radical and inflammatory processes, thus further degrading brain cell health and function.

Several supplements promote increased cerebral vascular blood flow and address the age-associated and lifestyle-accelerated decline in blood flow to, and circulation throughout, the brain. These supplements include: vinpocetine, ginkgo, acetyl-l-carnitine, cocoa flavanols and possibly resveratrol, blueberry extracts, and EGCG (green tea).

Cortisol, the main stress hormone, is shown to kill brain cells. Supplements addressing stress-related cortisol overload which damage the memory cells in the hippocampus, include; Ashwangandha, PS, Alpha GPC, Rhodiola, Panax Ginseng, Holy Basil, Cordyceps sinensis (mushroom), DHEA and Relora®, a proprietary blend of Magnolia officinalis and Phellodendron amurense.

Glucose is a primary fuel for the brain. Blood sugar swings, and chronic high or low blood sugar levels all harm the brain, especially the hippocampal (memory) cells. There are several levels of blood sugar support. The first is reducing postprandial (after eating) blood sugar spikes, which are most damaging. White kidney bean extract (Phase 2, Phaseolus vulgaris, an alpha-amylase blocker), fiber (e.g., Glucomannan), chlorogenic acid (i.e., coffee & especially green coffee bean extract), gamma-tocopherol, American ginseng, and a combination of cinnamon, zinc and chromium, and others have been shown to slow down the release and/or uptake of sugar into the bloodstream after a snack or meal. Another important approach is to raise insulin sensitivity.  The most promising supplements include, alpha lipoic acid, chromium picolinate, cinnamon, vitamin B-1 (thiamine) and especially the fat soluble form, benfotiamine, and resveratrol. Minerals manganese and vanadium may also help balance blood sugar.

A final level of attack is on reducing the formation of so called advanced glycation end-products (AGEs), insoluble plaques that can inflict major damage on the brain’s capillaries and neurons. Natural AGE inhibitors are pyridoxamine and pyridoxal 5’-phosphate (bioactive forms of Vit B-6), curcumin, alpha lipoic acid and possibly Vitamin C and taurine. Perhaps the best AGE-inhibitor is carnosine (beta-alanyl-L-histidine), a dipeptide formed naturally in human tissues, and available as a supplement.

Supplements addressing mitochondria breakdown and dysfunction, another primary cause of most brain and body cellular aging, include, acetyl-l-carnitine, vinpocetine, as well as alpha lipoic acid, CoQ10, creatine monohydrate, curcumin, N-acetyl-cysteine, and the newest entry, fisetin (as Novusetin™ from Cyvex) and others.

Supplements addressing brain (esp. microglial) inflammation are also very promising. These include curcumin, vinpocetine, blueberry and grape (anthocyanidins & OPCs), resveratrol, Fucoidan (from brown algae), olive (hydroxtyrosol) and possibly citrus polymethoxylated flavone.

Beta amyloid (Abeta) plaques are implicated in Alzheimer’s. Current opinion suggests they can begin formation in the brain long before symptoms of Alzheimer’s appear, although there’s great controversy whether they cause or contribute to Alzheimer’s, or merely represent collateral damage induced by other more direct causative factors. Nonetheless, attempts to reduce their formation, and/or neutralize their toxic by-products, e.g., free radicals, have been shown to improve memory. Supplements believed to down-regulate the production of Abeta and/or neutralize its generation of free radicals include; curcumin, acetyl-l-carnitine, Huperzine A, ginkgo biloba, Cat’s Claw, and others.

Coconut Cocktail


It’s been discovered that Alzheimer’s is characterized by neurons' reduced, if not total loss, in ability to utilize glucose as a primary fuel source. The glucose-starved brain cell is prone to dysfunction, breakdown and ultimate death. Supplements, e.g., vinpocetine, which can increase neuronal glucose uptake and utilization, thus perking up cerebral metabolism, are very promising.

Another most promising new approach provides the brain cells with a backup fuel, called ketones. This is readily accomplished with oral intake of MCT, or medium-chain triglycerides found in coconut oil. The liver converts MCT into “ketone bodies” which can fire up brain cells and even kick start their ability to efficiently use glucose once again.

Most exciting is the recent entry of a new medical food, a prescription powdered drink mix, or “cocktail” with the main active ingredient, MCT. It’s called Axona, from Accera Pharma, and is backed by Nestle. It has shown significant improvement in memory in an Alzheimer’s clinical trials.

Another exciting new medical food from MIT (& backed by Danone) is based on a cocktail promoting “synaptogensis” (repair & growth of synapses). Known as Souvenaid, it contains certain B vitamins, phospholipid choline and uridine (found in mother’s milk), along with the omega-3 fatty acid, DHA. These all act together to help create, strengthen and maintain synapses, and improve neurotransmission. It, too, has shown significant improvements in cognitive function in clinical Alzheimer’s trials.

Neurogenesis


The aging brain also suffers from reduced capacity to create new neurons, a process called neurogenesis. Neurotrophic agents that stimulate brain nerve growth factors (e.g., BDNFs) include; acetyl-l-carnitine and acetyl-l-carnitine arginate, blueberry extract, various ginsengs, coffee berry extract, hydroxytyrosol (from olive extract), Fisetin, Lion’s Mane and Nrf2 promoters (see below).

Cererbral Roto Rooters


Another promising approach are supplements that can help clear out the “debris” that clogs the delicate micro-capillaries providing brain cells the oxygen and vital nutrients they need on a steady basis. Such debris, likened to plaques that clog the heart’s arteries, include AGEs (advanced glycation end products), calcium (calcification), cholesterol and lipofuscin deposits (similar to the dark skin spots on the back of your hand). Supplements that may help reduce the formation of this debris, or even break it up and remove it, include, vinpocetine, DMAE, acetyl-l-carnitine, alpha lipoic acid, benfotiamine, curcumin, and especially carnosine.

Also important are the metal chelators that can bind to and remove toxic metals, e.g., mercury, lead, iron and aluminum. These chelation agents include: cilantro, curcumin, alpha lipoic acid, chlorella and sea weed alginates, N-acetyl-cysteine, taurine and vitamin C.

Cognitive Superstars?


Few supplements can be considered truly “neuro-pleiotropic.” That is, addressing multiple targets, or having multiple mechanisms of action in the brain. A few mentioned above, including, acetyl-l-carnitine, vinpocetine, huperzine A, alpha lipoic acid, Ashwagandha, Rhodiola and certain ginsengs seem to qualify. However, there’s a new “cognitive kid on the block” that may exceed the multiple brain health benefits of all the others, and at relatively small (50 mg) dosage levels.

Fisetin is considered a flavonol. Its primary sources are strawberries and the deciduous Japanese Wax Shrub/Tree (Rhus succedanea – L.). Fisetin (Novusetin™ from Cyvex) may offer the broadest number of brain benefits of any single ingredient yet discovered (by the Salk Research Inst.). Here’s a partial list of its many benefits:

1.           Master broad spectrum anti-inflammatory, uniquely within microglia

2.           Protects mitochondria from oxidative stress plus increases production of ATP

3.           Activates Sirtuin (Sir2) anti-aging proteins

4.           Increases brain oxygen levels

5.           Activates CREB processes enabling long term memory formation

6.           Increases cerebral vascular blood flow

7.           Initiates complex signaling for neural survival

8.           Initiates production of NGFs (nerve growth factors)

Next is a cousin to (trans) resveratrol, pterostilbene (methyl-resveratrol). Pterostilbene is a double-methylated version of the popular resveratrol, only it may possess significantly greater cell bioavailability. Pterostilbene has demonstrated broad anti-inflammatory and antioxidant actions via modulation of gene expression and enzyme activity. And, it seems to be much more available to the brain than the standard (trans) resveratrol.

Other supplements with relatively recent studies showing early promise for brain health and performance include:

•           Magnesium L-threonate (shown to be a more brain available form of magnesium, a vital nutrient for brain health)

•           Univestin (Scutellaria baicalensis and Acacia catechu) – a potent broad spectrum antioxidant and anti-inflammatory mix of two highly researched Asian herbs

•           Sea “greens”, such as Spirulina (phycocyanin), and Brown algaes, like Ecklonia cava (phlorotannins & phloroglucinol), Kombi & Wakame (fucoidan) - all demonstrating potent broad spectrum neuro-protective and brain boosting effects.

•           Tocotrienols (alpha, delta and gamma) are more recently researched isomers of the vitamin E family (with 8 isomers). The tocotrienols appear to be far superior to the long touted brain benefits of conventional “Vitamin E”, which in many, if not most studies is a synthetic version called alpha-tocopherol succinate or acetate. This may also explain why so many Vitamin E studies have been inconclusive - they did not use the natural, let alone tocotrienol form.

•           Nrf2 promoters: Nrf2 is a nuclear transcription factor that, when activated, can trigger a broad spectrum cascade of brain cell (neuro) protective antioxidants and Phase II detoxification enzymes (e.g., glutathione), increase cell survival and anti-inflammation signaling, and boost neurotrophic factors (promoting neurogensesis). Supplements that qualify as Nrf2 activators include; curcumin, rosemary (rosemarinic & carnosolic acid), resveratrol, pterostilbene & sulforaphane (from Broccoli, Brussels sprouts, cabbage et al), and the brown algae, Ecklonia cava (phlorotannins & phloroglucinols). WF

This article is not intended to diagnose or treat any disease. Always contact your healthcare provider before taking a new supplement.

Josh Reynolds is the Founder of Brain Research Labs, and the inventor of Procera AVH®, America's #1 Selling Brain Health & Performance supplement.

Josh pioneered the development and use of computerized online assessment and enhancement of brain function (“brain speed”), validated by Stanford and used by other medical schools, clinics and physicians (inc., Scripps, UC Irvine, Kaiser Permanente, Cenegenics, et al). His online tests have been used by millions for the assessment of IQ and brain power, and the detection of early memory loss, and have been administered to several thousand participants in numerous clinical studies to assess cognitive performance changes induced by a variety of nutraceutical agents.

Josh has invented, developed and clinically tested a half dozen brain health and performance enhancement supplements. He is the author of the medically reviewed book, 20/20 Brain Power, and has authored several peer reviewed abstracts and journal articles on brain health and cognitive function including the Society For Neuroscience, Journal of Intelligence and Journal of American Nutraceutical Ass. (JANA).

Josh lives in Laguna Beach, CA and can be reached via email – brainman001@gmail.com

Posted on WholeFoods Magazine Online, April 30, 2013