Brown Adipose Tissue - Support for Obesity Diabetes and Longevity

 In humans, there are two types of adipose tissue. White adipose tissue and brown adipose tissue. White adipose tissue is associated with excessive fat storage, obesity, insulin resistance and diabetes. Whereas, brown adipose tissue has the opposite effect - producing energy, reducing fat storage and obesity, while increasing insulin sensitivity and reducing diabetes. Further, increasing expression of brown adipose tissue (adipocytes) may also be correlated with increases in longevity.

Newborns have the greatest amount of brown fat, which helps provide a source of heat, but gradually decreases with age. Adults have a predominance of white adipose tissue which correlate with America's obesity epidemic.


  • White Adipocytes. Store fat (triglycerides) and is linked to obesity and associated metabolic disorders such as diabetes.
  • Brown and Beige Adipocytes. Energy and thermogenic producing cells. Activation of these cells offer a possible course of treatment for obesity and diabetes.(1)


  • Health benefits. Studies altering white adipocytes, into adipocytes with brown adipose tissue characteristics show dramatic changes. Includes improvement in increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. (2)
  • Longevity and UPC1. Aging studies involving animals, showed that increased expression of brown fat increases levels of UCP1 (uncoupling protein 1). UCP1 is contained in the membranes of mitochondria only in brown fat. When UCP1 is activated is provides an enormous source of heat energy.  Increased energy expenditure is recognized as a positive association with longevity.(3) Also UCP1 provides an alternative. less damaging path, for energy generation by the mitochondria. (see below). UCP1 protects the mitochondria from damaging oxidative stress and over a lifetime can have significant effect on lifespan.
  • Mitochondrial Uncoupling -Mitochondrial respiration, the process through which mitochondria produces energy,  also results in damaging end-products which promote cellular damage and death via free radicals - reactive oxygen species (ROS). The free radical theory of aging proposes that the free radicals produced by energy metabolism is linked to the aging process. Mitochondrial uncoupling describes anything which bypasses the normal electron chain which generates ATP energy and high levels of free radicals. Brown adipose tissue produces UCP1 - an important biological protein which enables mitochondrial uncoupling and reduction in damaging ROS generation.(3)



"Browning" of White Adipocytes.

Research indicates that fat storing white adipocytes may be altered to take on the characteristics of energy producing brown adipocytes. Such changes to white adipocytes may be an effective strategy for reducing obesity and obesity related disorders (such as insulin resistance and diabetes). Improving insulin sensitivity is a factor not only in diabetes, but also considered significant in longevity.

  • Sulforaphane - In vitro experiments showed an increase in UCP1 expression (the marker for brown adipose tissue activity), in addition to increasing glucose uptake. (4)
  • Curcumin - Curucmin induces browning of white adipocytes as well as inhibition of new fat cell generation. (5)
  • Andrographolide - Enhances brown adipose tissue gene activation attenuating obesity. Improves insulin sensitivity.(6)

Increase in Mitochondria in Brown Fat during New Cell Formation (Adipogenesis)

Improvement in number and function of mitochondria during brown fat adipogenesis. This may result in higher energy brown adipose tissue enabling even a stronger thermogenic response

  • Anthocyanins (C3G) - Anthocyanins, and in particular the anthocyanin C3G, has been shown to have beneficial effects towards obesity via brown adipose tissue. The effect is believed to be enhanced through increased mitochondria biogenesis during the formation of brown adipose tissue. (7)


XGEVITY   Glucoraphanin (precursor of Sulforaphane)

CURCUMIN XTRA-MAX  (includes Andrographolide)

BLUE NATURALLY   (high anthocyanins and C3G)



(1) Inagaki T, et al. Transcriptional and epigenetic control of brown and beige adipose cell fate and function. Nat Rev Mol Cell Biol. 2016 Jun 2

(2) Qian SW, et al. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis. Proc Natl Acad Sci USA. 2013 Feb

(3) Mookerjee SA, et al. Mitochondrial Uncoupling and Lifespan. Mech Ageing Dev. 2010 Jul - Aug.

(4) Zhang HQ, et al. Sulforaphane induces adipocyte browning and promotes glucose and lipid utilization. Mol Nutr Food Res. 2016 May 24

(5) Lone J, et al. Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes. J Nutr Biochem. 2016 Jan

(6) Ding L, et al. Andrographolide prevents high-fat diet-induced obesity in C57BL/6 mice by suppressing the sterol regulatory element-binding protein pathway. J Pharmacol Exp Ther. 2014 Nov

(7) You Y, et al. Mulberry and mulberry wine extract increase the number of mitochondria during brown adipogenesis. Food Funct. 2015 Feb

Chemicals and Pesticides - Impact on Brain Aging & Neurodegeneration

Aging and degeneration of the brain is affected by both internal and environmental factors. This includes the pesticide residue found on foods. Disruption of brain homeostasis, associated with aging,  results in amyloid plaques and neuro fibrillary tangles. However, the wide pervasiveness of chemicals, including pesticides, in our modern age are now suspected of playing a major role in neurodegenerative diseases. An important source of chemicals are the pesticides which are pervasive in our environment and food.

Chemicals have been associated with Parkinson's Disease, autism, Alzheimer's Disease and Huntington's Disease. In fact, environmental chemicals affect the brain in a similar manner as aging. Chemicals act by disrupting the microtubules in the neurons through an increase in free radical generation.(1)

Microtubules play a significant role in brain plasticity and neurodegenerative diseases. Researchers suggest that microtubules may be an effective target for neurodegenerative diseases. (2) Microtubules form a structural scaffolding in a healthy brain and are essential for brain function.

Studies indicate that the impact of chemicals on microtubules in the neurons can be reduced, and microtubules stabilized, by pretreatment with sulforaphane.(1)


XGEVITY  (with Sulforaphane precursor Glucoraphanin)



(1) Pearson BL, et al. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration. Nat. Commun. 2016 Mar 31;

(2) Penazzi L, et al. Microtubule Dynamics in Neuronal Development, Plasticity, and Neurodegeneration. Int Rev Cell Mol Biol. 2016

Sulforaphane - Inhibiting Glycation New Target for Alzheimer's Disease

Alzheimer's Disease (AD) and other neurodegenerative diseases, involve a complex etiology in both the initiation and progression of the disease. In AD known disease factors involve amyloid plaques, neurotangles (fibrils), inflammation and oxidative stress. Further research into this disease indicates that glycation of the amyloid, neurotangles and neurons may dramatically escalate destruction of the brain and accelerate disease progression. Mitigating glycation in the brain provides another target in the prevention of neurodegenerative diseases.

SULFORAPHANE targets the effects of oxidative stress and inflammation, both dominating factors in degenerative brain disease, including reduction of damage attributed to  the damaging glycation. Glycation of proteins, which occurs by the irreversible attachment of sugar to causes an accumulation of damaged brain proteins and is believed to be an important causative factor in AD.(1)

  • Methylglyoxal (MG) - the role in Alzheimer's Disease. Glycated proteins lead to the formation of toxic Advanced Glycation Endproducts (AGEs) and are a significant source of inflammation. AGEs are found in high amounts in  the brains of Alzheimer's patients in conjunction with amyloid plaques and neurotangles.Methylglyoxal (MD) is a potent precursor of AGEs and is directly responsible for increased oxidative stress and deterioration of brain function.
  • Sulforaphane increases cellular protection and enhances Methylglyoxal breakdown. Sulforaphane protects the brain by multiple paths.
      1. Increases critical levels of intracellular glutathione -offering significant protection to the neurons including reduction of neuron death.
      2. Increases breakdown of MG by elevating enzyme glyoxalase activity. 
      3. Increases Brain Derived Neurotrophic Factor (BDNF). BDFN, which is neuro protective, and is reduced in AD patients. Lower BDNF levels are considered a biomarker for Alzheimer's.
      4. Maintains critical glucose uptake for neuron energy. Methylglyoxal blocks important glucose uptake by the neurons which is  totally reversed by sulforaphane. When neurons are deprived of glucose (their main energy source) they can not survive.
    •  Sulforaphane also is an inhibitory of neuroinflammation. Using human micro-glia like cells, sulforaphane has been shown to inhibit the proinflammatory cascade triggered by beta-amyloid peptides, thereby significantly reducing damaging inflammation occurring in the AD brain.(2)


    XGEVITY (Glucoraphanin precursor to Sulforaphane)



    (1) Angeloni C, et al. Antiglycative activity of sulforaphane: a new avenue to counteract neurodegeneration? Neural Regen Res. 2015 Nov.

    (2) An YW, et al. Sulforaphane exerts its anti-inflammatory effect against amyloid-β peptide via STAT-1 dephosphorylation and activation of Nrf2/HO-1 cascade in human THP-1 macrophages. Neurobiol Aging 2016 Feb;

    Aging Stem Cells - The loss of Regenerative Ability & Aging

    Aging is suppressed through the ability of the body to regenerate more youthful cells and tissues. Extreme longevity is closely coupled to the ability of the body to replace aging cells, which lead to disease and aging, with youthful healthy cells. The capacity to regenerate cells depends on the ability of the body to maintain a healthy functioning pool of stem cells. Stem cells are the precursor cells which generate new replacement cells. For example, neural stem cells (NSC) can rejuvenate the brain by creating new brain cells.

    However, aging stem cells progressively lose the ability to generate replacement cells. More precisely, aging stem cells lose the ability to segregate damaged molecules during cellular replication, thereby diminishing the ability of stem cells to proliferate into new replacement cells. Sulforaphane has been shown to partially reverse detrimental cellular changes in stem cells, which may be able to restore stem cell function and cellular rejuvenation.

    In addition to extreme longevity, healthy stem cells may also support stem cell therapy, which depends on the proliferation ability of stem cells to heal damaged tissue.


    XGEVITY (Sulforaphane precursor Glucoraphanin)

    AIR VITALITY (Sulforaphane precursor Glucoraphanin)



    (1) Mendelsohn AR, et al. Aging Stem Cells Lose the Capability to Distribute Damaged Proteins Asymmetrically. Rejuvenation Res. 2015 Dec

    Brain & Neurodegenerative Diseases - The Central Role of Mitochondria

    All aging starts at the cellular level including degeneration of the brain. Science has now identified dysfunction of the neuron mitochondria as the early central initiator in brain degeneration. When the neuronal mitochondria become dysfunctional, there is an inadequate supply of energy to the neuron, and subsequently the neuron dies. Early stages of neurodegenerative diseases have mitochondrial dysfunction common in their pathogenesis including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and amyotrophic lateral sclerosis (ALS). Indeed, the failure of cellular bioenergetics has been linked to neuron death and dementia.(1,2)

    Research suggests that modulation and inhibition of mitochondrial dysfunction may increase neuron survival and provide a basis for extended brain longevity. As a cytoprotective agent, activation of transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2) protects the functioning of the mitochondria and is viewed as a target for possible prevention and treatment of neurodegenerative diseases associated with aging. Sulforaphane (and precursor Glucoraphanin) is one of the most powerful natural nrf2 activators, and may play a role in the intervention of age-related brain degeneration. (2) In addition, the natural extract andrographolide, carnosic acid and carnosol have been identified as a very strong nrf2 activators. (3, 4)



    Both Contain the following nrf2 activators:

    • Glucoraphanin / sulforaphane – from broccoli
    • Andrographolide – from andrographis paniculata
    • Carnosol & Carnosic Acid – from rosemary extract



    (1) Grimm A, et al. Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer's disease. Biogerontology. 2015 Oct 14.
    (2) Denzer I, et al. Modulation of mitochondrial dysfunction in neurodegenerative diseases via activation of nuclear factor erythroid-2-related factor 2 by food-derived compounds.
    Pharmacol Res. 2015 Nov 25.
    (3) Wu KC, et al. Screening of natural compounds as activators of the keap1-nrf2 pathway.
    Planta Med. 2014
    (4) de Oliveira MR. The Dietary Components Carnosic Acid and Carnosol as Neuroprotective Agents: a Mechanistic View. Mol Neurobiol. 2015 Nov 9



    Naked Mole Rats - Clues to their Exceptional Longevity

    Naked Mole Rats (NMR),  native to parts of East Africa, are extremely long lived rodents, living up to 8x's longer than comparably sized mice. This is equivalent to a humans living to be 800 years! Better yet, the NMR maintain their vitality and health to almost the end of their lives, including brains which are resistant to degeneration. So, what is behind such extreme longevity?

    The key is enhanced cellular protein homeostasis. (1-3) Key regulators of the aging process is the ability to maintain cellular quality including the removal of defective, damaged and toxic proteins. In the cell, proteasomes, the cellular machinery which removes damaged protein in conjunction with lysosomal  autophagy are involved in the removal of damaged protein and cellular components. NMR maintain a very high level of protein homeostasis by enhanced activity of proteasomes and maintaining high active levels of autophagy.

    Increased proteasome and autophagy activity extends lifespans in animal experiments. However, dysfunction of protein homeostasis increases with age, and leads to cellular accumulation of damaged protein, and the onset of disease and aging. In Alzheimer's Disease, for example, damaged proteins (amyloid and tau proteins) begin to aggregate, and eventually kill the surrounding neurons. Normal protein homeostasis is disrupted in Alzheimer's Disease, and most notably impairment of autophagy.(4)  

    PROTEIN HOMEOSTASIS is essential for extreme longevity. The two primary molecular mechanisms for maintaining health cell quality control and protein are: Proteasomes and Autophagy. "Aging is considered to be the loss of physiological integrity accompanied by a cumulative dysfunction in securing cellular homeostasis, resulting in the accumulation of damage and a progressive decline of cellular function over time." (7) 

    • Proteasomes-  In the cell it is the function of structures called proteasomes, to identify and remove damaged proteins.  Damaged proteins are tagged and then subsequently degraded by the proteasomes. Aging creates an imbalance in protein homeostasis, whereby proteasomes become dysfunctional.
    • Autophagy - Is the quality control in the cell which removes and recycles damaged and non-functional components (organelles and protein) through lysosomal degradation. Animals studies clearly demonstrate that in autophagy deficient mutants, lifespan is significantly reduced. Autophagy works in conjunction with protesomes  to maintain cellular health and extend longevity.
    • Heat Shock Proteins (HSP) - HSP are involved as sentries and chaperons, which monitor the cell for damaged proteins and ensure that they are rapidly degraded and recycled. HSPs work in conjunction with the proteasome system to prevent the accumulation of misfolded and toxic proteins in the cell. HSP identifies damaged misfolded proteins for proteasome degradation. HSP increase longevity, however levels decrease with aging.(10,11)

      FOXO Nrf2 (transcription factors) AND PROTEIN HOMEOSTASIS:

      • FOXO transcription factors are key regulators of cellular quality control including protein homeostasis
      • FOXO is required for the activation of proteasome and autophagy. (5,12)
      • Nrf2 is key for maximal expression of proteasomes for cellular protein homeostasis.(13)
      • Sulforaphane increases both proteasome activity and autophagy.(10) Increased activation of Nrf2 by sulforaphane is an important pathway by which proteasomal activity is increased.(9,11) Also sulforaphane upregulates heat shock proteins (HSP), which further elevates the protein degradation functioning of the proteasomes.(14)
      • Curcumin supports protein homeostasis through enhanced autophagy and HSP (Heat stress proteins)(16, 17)) and Nrf2 activation (13).
      • Resveratrol and Calorie Restriction also increase autophagy and extend lifespan.(15)


        XGEVITY (Glucoraphanin / Sulforaphane)

        AIR VITALITY (Glucoraphanin / Sulforaphane)


        PURPLE LONGEVITY (Resveratrol)



        (1) Triplett JC, et al. Age-related changes in the proteostasis network in the brain of the nakedmole-rat. Implications promoting healthy longevity. BiochimBiophys Acta. 2015 Oct.

        (2) Triplett JC, et al. Metabolic clues to salubrious longevity in the brain of the longest-lived rodent: the naked mole-rat. J Neurochem. 2015 Aug.

        (3) Pride H, et al. Long-lived species have improved proteostasis compared to phylogenetically-related shorter lived species. Biochem Biophys Res. Commun. 2015 Feb.

        (4) Chondrogianni N, et al. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans. FASEB J. 2015 Feb

        (5) Chondrogianni N, et al. Enhanced proteasome degradation extends Caenorhabditis elegans lifespan and alleviates aggregation-related pathologies. Free Radic Biol Med. 2014 Oct.

        (6) Salminen A, et al. Impaired autophagy and APP processing in Alzheimer's disease: The potential role of Beclin 1 interactome. Prog. Neurobiol. 2013 Jul-Aug;

        (7) Grimmel M, et al. WIPI-Mediated Autophagy and Longevity. Cells. 2015 May.

        (8) Liu Y, et al. Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington's disease. J Neurochem 2014 May

        (9) Chapple SJ, et al. Crosstalk between Nrf2 and the proteasome: therapeutic potential of Nrf2 inducers in vascular disease and aging. Int J Biochem Cell Biol. 2012 Aug

        (10) Murshid A, et al. Stress proteins in aging and life span. Int J Hyperthermia. 2013 Aug.

        (11) Calderwood SK, et al. The shock of aging: molecular chaperones and the heat shock response in longevity and aging--a mini-review. Gerontology. 2009.

        (12) Webb AE, et al. FOXO transcription factors: key regulators of cellular quality control. Trends Biochem Sci. 2014 Apr.

        (13) Pickering AM, et al. Nrf2-dependent induction of proteasome and Pa28αβ regulator are required for adaptation to oxidative stress. J Biol Chem. 2012 Mar.

        (14) Gan N, et al. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27. J Biol Chem. 2010 Nov.

        (15) Testa G, et al. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr. Pharm Des. 2014

        (16) Petrovski G, et al. Does autophagy take a front seat in lifespan extension? J Cell Mol Med. 2010 Nov

        (17) Alavez S, et al. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature. 2011 Apr.

        Atrial Fibrillation : Effects of Aging and Endurance Sports

        ATRIAL FIBRILLATION (AF) is the most common arrhythmia of the heart and is caused when the atrial contraction becomes out of sync with the ventricle due to dysfunctional electrical signaling. The result is the ineffective movement of blood through the body. Atrial fibrillation may result in a fast fluttering heartbeat, which is a common characteristic. Because the blood is not being pumped through the body properly, atrial fibrillation increases risk of heart failure and the pooling of blood in the heart, which increases chances of blood clot formation. Blood clots which travel to the brain may cause a stroke.

        Risk of atrial fibrillation increases with age which coincides with increased oxidative stress, where excessive free radicals exceed the body’s ability to protect against them. Oxidative stress activates inflammatory pathways and chronic inflammation. Mitochondrial production of free radicals is a major source of oxidative stress in the atrial cells. Onset of atrial fibrillation includes changes to the atrial myocardium which includes inflammation and fibrosis which effects changes to the electrical properties and loss of synchronization. Therefore, research suggests two important factors may play a role in the alteration of the atrial cells and electrical impulse: Oxidative stress and inflammation.


        • AGING: A prominent risk factor for atrial fibrillation is aging. Aging is correlated with increased levels of systemic oxidative stress and inflammation.
        • ENDURANCE EXERCISE: AF has an increased occurrence in athletes, in particular those involved in endurance exercise (e.g. long distance running). The frequency of AF in endurance athletes is most notable in veteran endurance athletes (from ages 45 and higher). (1,2)
        • During endurance exercise, versus moderate exercise, repeated strenuous overloads of the atria result in microtears and consequently inflammation and fibrosis.(2)


        Inhibition of oxidative stress and inflammation of the artrial myocardial tissue, which reduces potential for fibrosis in the atria, are key in reducing the risk for atrial fibrillation. Beneficial steps:

        • INCREASING NRF2 – Nrf2 is a transcription factor which regulates the expression of proteins involved with cellular protection. Deficiency of Nrf2 reduces levels of protective proteins and facilitates the pathogenesis of structural changes to the atrial tissue, including fibrosis.(3-6) The condition of AF continues the cycle of oxidative stress, further altering the atrial tissue.
        • INHIBITION OF INFLAMMATION. TNF-alpha and NK-BKappa are signaling proteins which are central to the inflammatory pathway activation. TNF-alpha plays an important role in the pathogenesis of atrial structural changes and atrial fibrillation.(6)
        • ROLE OF NRF2 ACTIVATORS such as sulforaphane (and precursor glucoraphanin), supports the reduction of the tissue oxidative state while concurrently reducing the activation of the formation of fibrotic atrial tissue.(3-6) The Nrf2 activators, as powerful cell protectors, also support inflammation reduction and decrease expression of proinflammatory TNF-Alpha and NF-KappaB,
        • RESVERATROL may also have direct effects on cardiac function and the pathways that affect the structural changes to the atria. Recent research indicates that resveratrol may inhibit changes to the atria with decreased atrial fibrosis formation.(7-8)

        XGEVITY    (Glucoraphanin / Sulforaphane plus other Nrf2 activators)

        PURPLE LONGEVITY    (Resveratrol plus Nrf2 activators)



        (1) Laszio R, et al. Atrial fibrillation and physical activity: An overview. Herz. 2015 Sept.
        (2) Redpath CJ, et al. Atrial fibrillation and the athletic heart. Curr Opin Cardiol. 2015 Jan.
        (3) Hecker L, et al. Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med. 2014 Apr
        (4) Wolke C, et al. Redox control of cardiac remodeling in atrial fibrillation. Biochim Biophys Acta. 2015 Aug;
        (5) Yeh YH, et al. Rosuvastatin suppresses atrial tachycardia-induced cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway. J Mol Cell Cardiol. 2015 May.
        (6) Ren M, et al. Role of tumor necrosis factor alpha in the pathogenesis of atrial fibrillation: A novel potential therapeutic target? Ann Med. 2015 Jun
        (7) Baczkó I, et al. Resveratrol and derivatives for the treatment of atrial fibrillation. Ann N Y Acad Sci. 2015 Aug
        (8) Chong E, et al. Resveratrol, a red wine antioxidant, reduces atrial fibrillation susceptibility in the failing heart by PI3K/AKT/eNOS signaling pathway activation. Heart Rhythm. 2015 May