The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 19 No. 5 • June 2016


It may seem a long time that you’ve been reading about neurogenesis, the process whereby new neurons are created in the adult brain, but it is an amazingly few years—a little less than 20 years—since the first papers with direct evidence of neurogenesis began to appear on this subject. At the time, it was considered quite controversial, whereas now it is well established and the subject of some 41,962 papers in the literature as of today, May 14, 2016. For example, one of the earliest papers demonstrating that an enriched environment would result in the creation of new neurons in the adult brain (of mice) was published in 1998. “Neurogenesis was a hard thing for scientists to come to grips with,” said Fred Gage, a scientist at the time at the Salk Institute, who was a very early pioneer in the experimental work establishing neurogenesis. (Schwartz, 2002)

Later work was published showing that neurogenesis didn’t occur just in mice, but in humans as well. It came as quite a surprise to scientists, with its promise of improved cognition in both young and old.

These days, we are seeing ever more publications on ways to enhance neurogenesis, including a small number involving the use of nutrients or herbs that are safe and readily available. For instance, in one study (Tian, 2012), mice were lesioned with the neurotoxin 6-OHDA (6-hydroxydopamine), damaging and killing dopaminergic neurons. They were implanted with dopaminergic neurons and treated (or not) with sodium selenite. “The expression level of TNF-alpha [tumor necrosis factor alpha, an inflammatory cytokine] and iNOS [inducible nitric oxide synthase, an inflammatory factor] were decreased by 30% and 50%, respectively, in selenite treated group. The survival of implanted DA [dopamine] neurons and the rotational behavior of transplanted rats were also remarkably improved by selenite treatment.” Another paper (Molina-Holgado, 2007) reported that the expression of CB2 (cannabinoid receptor 2) promoted the proliferation of mouse neural stem cells. Activators of CB2 are found in a typical diet and include caryophyllene, a common constitutient of many culinary herbs (cloves, caraway, hops, basil, rosemary, cinnamon), and fruits and vegetables.

Another nutrient that has been found to enhance the numbers of newborn neurons and to protect them from the culling process that kills most newborn neurons is hesperidin. (Pathak, 2013) Hesperidin is a flavonone glycoside found abundantly in citrus fruits. It has a variety of protective properties including decreasing the permeability of capillaries, helping to prevent easy bruising. “Another study has shown the involvement of kappa opioidergic receptors in the antidepressant-like effect of hesperidin.” “Hesperidin seems to be a viable candidate for the treatment of major depression.” (Pathak, 2013) Our LITHIUM PLUS™ is one source of hesperidin.


A potential benefit of voluntary running was described in a 2008 paper (Naylor, 2008). Young mice were exposed to radiation and then, after eight weeks, allowed to run freely in a running wheel. Though there was no difference in the distance the animals ran as compared to nonirradiated mice, the authors reported: “Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation.” “Interestingly, voluntary running significantly increased the number of stem cells after irradiation...” (Naylor, 2008)

This particular study did not examine whether FORCED running would have similar effects (see Santos-Soto, 2013, described in the section above, where the anxiety reducing effects of voluntary running were not duplicated in animals subject to forced, rather than voluntary, running. This points to the complexity of brain processing. It isn’t just the motor activity that produces the beneficial effects, but other areas of the brain associated with the recognition of coercion also help determine how the motor information is interpreted and which biochemical pathways are then activated.


  • Bartzokis. Neuropharmacology: myelination as a shared mechanism of action of psychotropic treatments. Neuropharmacology. 62(7):2137-53 (2012).
  • Coates and Herbert. Endogenous steroids and financial risk taking on a London trading floor. Proc Natl Acad Sci U S A. 105(16):6167-72 (2008).
  • Draganski, Gaser, et al. Changes in grey matter induced by training. Nature. 427:311-312 (2004).
  • Fields. Change in the brain’s white matter. Science. 330:768-769 (2010).
  • Fuhr et al. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol. 35:431-6 (1993).
  • Habbas, Santello et al, Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling. Cell. 163:1730-41 (2015).
  • Hashim and VanItallie. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. J Lipid Res. 55:1818-26 (2014).
  • Hen et al. J Neurosci. Feb. 6, 2008 (as reported in Science News, Feb. 9, 2008 (p. 83)
  • Henderson et al. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond). 6:31 (2009).
  • Henderson and Poirier. Pharmacologic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mind to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 12:137 (2011).
  • Hucklenbroich, Klein, et al. Aromatic turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Res Ther. 5:100 (2014).
  • Itoh, Imano, et al. (-)-Epigallocatechin-3-gallate increases the number of neural stem cells around the damaged area after rat traumatic brain injury. J Neural Transm. 119:877-90 (2012).
  • Kempermann, Kuhn, and Gage. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci. 18(9):3206-12 (1998).
  • Klosinski et al. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer’s disease. EBioMedicine. 2:1888-904 (2015).
  • Maalouf et al. The neuroprotective properties of caloric restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 59(2):293-315 (2009).
  • Mobbs, Petrovic, et al. When fear is near: Threat imminence elicits prefrontal-periaqueductal gray shifts in humans. Science. 317(5841):1079-83 (2007).
  • Morrone et al. Interaction between therapeutic interventions for Alzheimer’s disease and physiological Abeta clearance mechanisms. Front Aging Neurosci. 7 (article 64), (2015).
  • Naylor, Bull, et al. Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A. 105(38):14632-7 (2008).
  • Newport et al. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s. Alzheimers Dement. 11(1):99-103 (2015).
  • Osso and Chan. Astrocytes underlie neuroinflammatory memory impairment. Cell. 163:1574-6 (2015).
  • Paoli et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 67:789-96 (2013).
  • Santos-Soto et al. Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex. PLoS ONE. 8(12):e81459 (2013).
  • Westman et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 5:36 (2008).
  • Yoo, Choi, et al. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res. 24:1065-70 (2010).

Featured Product

  • Learn more about Hesperidin benefits and implementation strategies.

Ingredients in this Article

FREE Subscription

  • You're just getting started! We have published thousands of scientific health articles. Stay updated and maintain your health.

    It's free to your e-mail inbox and you can unsubscribe at any time.
    Loading Indicator