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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.

ADIPOCYTES COMPARISON

  • 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)

BROWN ADIPOSE TISSUE

  • 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)

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NUTRITION SUPPLEMENT SUPPORT:

"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)

 

REFERENCES:

(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

Natural Support for Inflammatory Skin Diseases - Psoriasis and Eczema

INFLAMMATION OF THE SKIN Common forms of inflammatory skin diseases include psoriasis and eczema. Primary common features of these diseases include chronic inflammation, including break down of the skin barrier, dryness and redness and itchiness. Hyper proliferation of skin cells, adding a thickness to the affected areas, is also common, and caused by inflammatory factors.

Psoriasis and eczema are both immune initiated diseases involving lymphocytes (T-Cells: TH1. TH2 and TH17), which cause the secretion of pro-inflammatory factors (called cytokines). The T-cells migrate into the skin where they chronically secret inflammatory factors which inflame the skin. Among the methods to reduce skin inflammation is to decrease the proliferation of T-cells in the skin and to prevent the secretion of pro-inflammatory cytokines.  While both psoriasis and eczema are immune T-cell based diseases, the causative basis of the immune response are not the same, and therefore the effects and targets are different.(1)

 

  • PSORIASIS. An autoimmune disease, which is associated with activation of the TH1 and TH17 lymphocytes. The presence of TH1/TH17 occur is high amounts in autoimmune diseases. Inflammatory skin diseases are characterized by dry, itchy and red skin are caused by an abnormal inflammation response in the body.  Psoriasis is a common form of inflammatory skin disease and is symptomatic of an autoimmune disease and may further indicate the presence of other autoimmune conditions such as rheumatoid arthritis.
  • ECZEMA. An allergic response of lymphocytes in the skin. In contrast with psoriasis, eczema is characterized by activation of TH2 lymphocytes. Also inflammatory cytokines IL-4, IL-6 and IL-13 are increased in eczema (atopic dermatitis).
  • Inflammatory Factors. While there are a number of inflammatory cytokines involved in the inflammation of the skin, a particular key one is TNF-α (TNF-alpha). Studies show high levels of TNF-alpha in the inflamed skin. Not only is TNF-alpha derived from the immune cells, but also has a feedback mechanism which further strengthens the pathological response of the activated T-cells (especially increasing differentiation of TH17). (2)

 

INGREDIENT SUPPORT:

  • Curcumin - Significantly inhibted T-cell secretion of pro-inflammatory factors, including TNF-alpha, by 30-60%. Furthermore, inhibited 50% T-cell proliferation.(3) Oral treatment with curcumin significantly reduced a key psoriasis inflammation factor IL-22. Keratinocyte (skin cell) proliferation in psoriasis is due to IL-22. (4,5) No side effects reported from curcumin (3). Also shown to suppress TH1 induce inflammation in skin cells.(6)
  • Andrographolide Supports homeostasis of TH1 / TH2 /TH17 (11). Also effective against rheumatoid arthritis (an autommune disease by suppressing TH17)(8, 9)
  • Schisandra Supports suppression of Th2 invoking an anti-allergic effect.(10) Further, schisandra effectively reduced inflammatory Th2 inflammatory cytokines IL-4 and IL-13 as well as TNF-alpha and IL-6 in research studies on inflammatory skin disease.(11). In particular IL-4 and IL-13 are the focus of new drug development for atopic dermatitis.(12)
  • Anthocyanins with C3G (Blueberry, other dark berries) 
    Suppresses levels of TH2 cytokines and TH17.(13-15)

NOTE: In contrast to natural ingredients, standard immunosuppressive drugs (which reduce the immune response, and are marketed for psoriasis) may have side effects, including kidney fibrosis.(16)

 

CURCUMIN XTRA-MAX (BCM-95 Curcumin, Andrographolide, Schisandra)

BLUE NATURALLY (C3G and other anthocyanins)

 

 

REFERENCES:

(1) Coimbra S, et al. A specific molecular signature for psoriasis and eczema. Annals of Translational Medicine. 2015 Apr.

(2) Ke F, et al. Soluble Tumor Necrosis Factor Receptor 1 Released by Skin-Derived Mesenchymal Stem Cells Is Critical for Inhibiting Th17 Cell Differentiation. Stem Cells Transl Med. 2016 Jan 27

(3) Kang D, et al. Curcumin shows excellent therapeutic effect on psoriasis in mouse model. Biochimie. 2016 January 27.

(4) Zhao Y, et al. Curcumin inhibits proliferation of interleukin-22-treated HaCaT cells. Int J Clin Exp Med. 2015 Jun 

(5) Antiga E, et al. Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris. Biomed Res Int. 2015.

(6) Sun J, et al. Curcumin relieves TPA-induced Th1 inflammation in K14-VEGF transgenic mice. Int. Immunopharmacol. 2015 Apr.

(7) Zhang C, et al. Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance. Int. Immunopharmacol. 2013 Aug.

(8) Liu W, et al. Andrographolide sulfonate ameliorates experimental colitis in mice by inhibiting Th1/Th17 response. Int Immunopharmacol. 2014 Jun

(9) Ku CM, et al. Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes. Food Chem. 2013 Nov 15

(10) Lee KP. et al. Anti-allergic effect of α-cubebenoate isolated from Schisandra chinensis using in vivo and in vitro experiments. J Ethnopharmacol. 2015 Sep

(11) Lee HJ, et al. Effects of Schisandra chinensis Turcz. fruit on contact dermatitis induced by dinitrofluorobenzene in mice. Mol Med Rep. 2015 Aug

(12) Lauffer F, et al. Target-oriented therapy: Emerging drugs for atopic dermatitis. Expert Opin Emerg. Drugs. 2016 Jan 25.

(13) Pyo MY, et al. Cyanidin-3-glucoside suppresses Th2 cytokines and GATA-3 transcription factor in EL-4 T cells. Biosci Biotechnol Biochem 2014

(14) Kim MJ, et al. Mixture of Polyphenols and Anthocyanins from Vaccinium uliginosum L. Alleviates DNCB-Induced Atopic Dermatitis in NC/Nga Mice. Evid. Based Complement Alternat. Med. 2012.

(15) Min HK, et al. Anthocyanin Extracted from Black Soybean Seed Coats Prevents Autoimmune Arthritis by Suppressing the Development of Th17 Cells and Synthesis of Proinflammatory Cytokines by Such Cells, via Inhibition of NF-κB. PLoS One. 2015 Nov 6

(16)  Kedzierska K, et al. The effect of immunosuppressive therapy on renal cell apoptosis in native rat kidneys. Histol Histopathol. 2015 Jan.