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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:

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)

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

Remarkable Vinpocetine & Citrus Bergamot - Youthful Arteries and Suppressing Atherosclerosis

Arteries degenerate with age, via a process known as vascular remodeling, leading to atherosclerosis, stroke and other cardiovascular diseases.. Therefore, preserving youthful arteries is a very important factor in longevity. Two important supplements which have been shown to suppress degenerative changes to the arteries are vinpocetine and citrus bergamot polyphenols.

VASCULAR AGING - Involves changes to the vascular endothelium and smooth muscle which promotes increased hypertension and stiffness of the arteries. The results is an aged vascular system  which is characterized by inflammation and atherosclerosis. As such, the arteries lose their ability to expand and contract, and becomes stiff, thickened and inflamed. When the vascular system ages it becomes more susceptible to hypertension, ischemic stroke and coronary heart blockage (heart attack). Furthermore, vascular aging in the brain may lead to cognitive disorders due to diminished blood flow.

Key areas of Vascular Aging:

• NF-kB - The master transcription factor for promoting inflammation in the artery and is involved in atherosclerosis plaque progression.
• PDE1 (phosphodiesterase) - An isozyme which plays a key role in the pathological changes which occur in the vascular structure with age. Increased levels of PDE1 are associated with loss of vasodilator function, vascular smooth muscle senescence, increased blood pressure and vascular hypertrophy. (1,2)

VINPOCETINE -
Promotes youthful arteries via two mechanisms. Vinpocetine reduces the release of inflammatory cytokines from endothelial cells and vascular smooth muscle by targeting oxidative stress and inflammation of the arteries. NF-kB. Also, vinpocetine is a powerful inhibitor of PDE1.

• Suppresses Atherosclerosis - Via the inhibition of inflammation transcription factor NF-kB.(3)
• Inhibition of PDE1 - PDE1 is a key regulator in the pathological changes that occur in aging vascular functioning including changes to structure and blockage of blood flow. Aging (senescent) vascular cells are correlated with increased levels of PDE1. (4) Inhibition of PDE1 has been shown to reduce all biomarkers associated with vascular aging.

CITRUS BERGAMOT (Bergamonte®) - The polyphenols in Citrus Bergamot uniquely provide artery anti-aging benefits. Citrus Bergamot provides protection directly to the vascular endothelium, in addition to optimizing cholesterol and triglycerides and inhibiting non alcoholic liver disease.

• Vascular Endothelium Protection.  Targets arterial endothelium cells to reduce inflammation and oxidative stress. Both are associated with vascular aging.
• Inhibits Non Alcoholic Fatty Liver Disease (NAFLD). NAFLD is a common liver disease where fat accumulates in the liver, causing liver dysfunction and is correlated with increased cardiovascular disease and mortality. It is estimated that up to 25% of Americans have NAFLD. Furthermore, excess belly fat not only is predictor of increased cardiovascular risk, but normally indicates high fat in the liver and NAFLD.
• Bergamot polyphenols stimulate lipid metabolism thereby preventing toxic build-up in the liver. Removal of lipids is through enhanced autophagy. (6)
  
• Decreases Oxidized Cholesterol Receptors. LOX-1 is the receptor on the endothelium for oxidized cholesterol. Expression of LOX-1 is increased with pathological conditions including hypertenison, hyperlipidemia, and diabetes.(5, 7)
• Inhibits Phosphodiesterases (PDEs). Offers similar protections as vinpocetine in preventing age-related changes to vascular structure .(7)

 VASCULAR STRENGTH  (with Vinpocetine and Bergamot Polyphenols)

REFERENCES:

(1) Chan S, et al. PDE1 isozymes, key regulators of pathological vascular remodeling. Curr Opin Pharmacol. 2011 Dec

(2) Bautista N, et al. Phosphodiesterase 1 regulation is a key mechanism in vascular aging. Clin Sci (Lond) 2015 Dec

(3) Zhuang J, et al. Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice. PLoS One. 2013 Dec.

(4) Yan, C. Cyclic nucleotide phosphodiesterase 1 and vascular aging. Clin Sci (Lond). 2015 Dec.

(5) Chen M, et al. LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis. Pharmacol Ther. 2002 Jul

(6) HP Ingredients. Support against NAFLD in those with Metabolic Syndrome. 2016 Apr.

(7) HP Ingredients. 2016.

Short Chain Fatty Acids - Optimizing Metabolic Energy and Longevity

How and to what extent microbes influence on health is a relatively new area of study. Amazingly,  the influence of gut microbiota on general health and longevity is only now becoming understood. Recent attention is scientific areas concern the importance of intestinal microbes and how they affect not only health of the the gut but also overall health of the body.(1) An area of keen interest is the production of Short Chain Fatty Acids (SCFAs) by microbial fermentation in the gut and how it can significantly improve health.(2)

Short Chain Fatty Acids (SCFAs - acetic acid, propionic acid and butyric acid) are produced as a fermentation byproduct of soluble fiber (e.g nuts, seeds, certain vegetables) by microbes in the large intestine.

Among the beneficial effects of SCFA's include:

• IMPROVES HEALTH OF INTESTINES. SCFA's are used as nutrients by the cells in the intestine to improve intestinal health, reducing inflammation and improving  gut barrier dysfunction. Gut barrier dysfunction contributes to chronic low grade inflammation and metabolic endotoxaemia.

• REDUCING INSULIN RESISTANCE - Insulin Resistance s a major factor in the development and disease progression in diabetes. Furthermore, insulin resistance is significant in aging, and loss of glucose homeostasis accelerates the aging process.(3)

• IMPROVING TYPE 2 DIABETES METABOLIC CONTROL - SCFA's are now considered as key molecules in mitigating some of the effects of diabetes including reduction in serum levels of glucose, insulin resistance. Furthermore, SCFA's increase the production of Glucogen-like Peptide-1 (GLP-1)  which is protective against diabetic effects. (4)
  

• OBESITY - Development of obesity is affected by decreased SCFA production by microbiota in the intestine. Increased gut permeability, inflammation and increased energy are significant contributors to obesity.

THE ROLE OF TAURINE IN SHORT CHAIN FATTY ACID PRODUCTION.

Furthermore, research indicates that taurine supplementation may significantly improve the intestinal microbiotic environment by increasing the production of SCFAs  and decreasing inflammatory concentrations of serum  lipopolysaccharides (LPS). LPS induced inflammation is a common issue facilitated by the processed western diet.(5)

LONGEVITY NATURALLY (High Taurine Complex)

REFERENCES:

(1) Andoh A. Physiological Role of Gut Microbiota for Maintaining Human Health. Digestion. 2016 Feb 9

(2) KeenanMJ, et al. Improving healthspan via changes in gut microbiota and fermentation. Age (Dordr). 2015 Oct.

(3) Hartl FU. Cellular Homeostasis and Aging. Annu Rev Biochem. 2016 Apr 6.

(4) Puddu A, et al. Evidence for the gut microbiota short-chain fatty acids as key pathophysiological molecules improving diabetes. Mediators Inflamm. 2014

(5) Yu H, et al. Effects of taurine on gut microbiota and metabolism in mice. Amino Acids. 2016 Mar 30. 

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)

REFERENCES:

(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

Anti-Stress Effects - Schisandra & Rhodiola Rosea

Exercise Performance - VO2Max for Performance with Age

As with most body functions, exercise performance decreases and muscle function decline with age. Key to anti-aging exercise is the maintenance of the ability of the heart to ensure power, balance, maximum oxygen consumption (VO2 max) and healthy blood pressure in humans.

• Arjuna Extract - Supports healthy heart muscle tone, and improves heart contraction ability. Arjuna has been shown to support endurance in athletic performance. In a study involving young adults, terminalia arjuna increased VO2 max. Further, authors of the study concluded that arjuna may enhance cardiovascular endurance and athletic performance.(1)

• Red Spinach Extract (Source of Nitrates) - Provides dual source of energy for mitochondria - for a surge in energy - and increase muscle efficiency during exercise.(2-4) In fact, red spinach has one of the highest concentrations of nitrates, (more than twice as high as beet root) with no oxalic acid / oxalate content.

Key Benefits of Red Spinach Extract

Magnesium Bisglycinate - Magnesium  supports health heart and artery function.

 CARDIO VITALITY

REFERENCES:

(1) Sandhu JS, et al.  Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults.. Int J Ayurveda Res.  2010 Jul;

(2) Arjuna Naturals ( Oxystorm^TM  ) Spinach Nitrates

(3) Reid MB. Redox interventions to increase exercise performance. J Physiol. 2015 Nov 20. 

(4) Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014 May

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)

REFERENCES:

(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;