Monthly Archives: February 2017

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A Multiprong Approach to Mild Cognitive Impairment – Prong One: Nutrients that Support Brain Function

According to the Mayo Clinic, Mild Cognitive Impairment (MCI) is defined as:

“Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more serious decline of dementia. It can involve problems with memory, language, thinking and judgment that are greater than normal age-related changes. If you have mild cognitive impairment, you may be aware that your memory or mental function has “slipped.” Your family and close friends also may notice a change. But generally these changes aren’t severe enough to interfere with your day-to-day life and usual activities.”   (Mayo Clinic)

In evaluating whether a patient has MCI, a diagnostic tool known as the 3.0 Tesla MRI (3T MRI) scanner is often used.  A 3T MRI reveals four conditions that result in a diagnosis of MCI:

  1. Atrophy, or shrinkage, resulting from the loss of cells in the brain,
  2. Demyelination, the loss of the sheathing that surrounds neurons, which protects them as insulation does copper wiring. Myelination, or the development of the sheath around neurons, continues until age 30; thereafter, demyelination, or deterioration of the sheathing occurs,
  3. Ischemia, the restriction of blood flow, and
  4. Calcification, the hardening of tissue resulting from calcium deposits.

In order to prevent and treat MCI, a multipronged approach is often taken by health care professionals.  The first prong for the prevention and treatment of MCI is the use of specific nutraceuticals that address the four conditions of MCI. 

In addition, supporting the four main brain neurotransmitters with specific nutrients and precursors is also important in the prevention and treatment of MCI.

The four main neurotransmitters are:

  • Dopamine (Power)
  • Acetylcholine (Speed)
  • GABA (Rhythm)
  • Serotonin (Mood)

It is apparent from the Table below that the following nutraceuticals address more than one of the seven brain functions:

  • Gastrodin
  • EPA/DHA
  • Magnesium-L-Threonate
  • Tocotrienols (Vitamin E)

 Table: Nutrients that Support Brain Function

Brain Function

 

 

 

 

 

 

 

 

Category

Nutrient

Neuro-genesis

Plasticity

Blood Circula-tion

Power

Speed

 

Rhythm

 

Mood

Amino Acids

 

 

 

 

 

 

 

 

 

L-Tyrosine

 

 

 

X

 

 

 

 

Acetyl-L-Carnitine Arginate

 

 

 

X

 

 

 

 

Acetyl-L-Carnitine

 

 

X

 

 

 

 

 

GABA

 

 

 

 

 

X

 

 

Tryptophan

 

 

 

 

 

 

X

 

5-Hydroxytrypto-

phan (5-HTP)

 

 

 

 

 

 

X

Foods

 

 

 

 

 

 

 

 

 

Berry extract

X

 

 

 

 

 

 

 

Blueberry Extract

 

X

 

 

 

 

 

Herbs

 

 

 

 

 

 

 

 

 

Gastrodin

X

 

 

 

 

X

 

 

Huperzine A

 

 

 

 

X

 

 

 

Ashwagandha

 

 

 

 

 

X

 

Hormones

 

 

 

 

 

 

 

 

 

Melatonin

 

 

 

 

 

 

X

 

Pregnenolone

 

 

 

 

 

 

X

Lipids

 

 

 

 

 

 

 

 

 

EPA/DHA

 

 

X

X

X

 

 

 

PhosphatidylSerine

X

 

 

 

 

 

 

Minerals

 

 

 

 

 

 

 

 

 

Magnesium L-Threonate

 

X

 

 

X

 

 

Nootropics

 

 

 

 

 

 

 

 

 

Vinpocetine

 

 

X

 

 

 

 

Nucleic Acids

 

 

 

 

 

 

 

 

 

Uridine-5’-Monophosphate

X

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyphenols

 

 

 

 

 

 

 

 

 

Resveratrol

X

 

 

 

 

 

 

 

Green Tea

X

 

 

 

 

 

 

 

Quercetin

X

 

 

 

 

 

 

 

Curcumin

X

 

 

 

 

 

 

Quinones

 

 

 

 

 

 

 

 

 

CoQ10

 

 

X

 

 

 

 

 

 

 

 

 

 

 

 

 

Vitamins

 

 

 

 

 

 

 

 

 

Folic Acid

 

 

 

X

 

 

 

 

Alpha-Glyceryl Phosphoryl Choline

 

 

 

 

X

 

 

 

Tocotrienols (Vitamin E)

 

X

 

 

X

 

 

 

Methylcobalamin

 

 

 

 

X

 

 

 

B Complex Vitamins

 

 

 

 

 

X

 

 

Inositol

 

 

 

 

 

X

 

 

Vitamin K

 

X

 

 

 

 

 

Source:  Reverse Mild Cognitive Impairment,  By Eric Braverman, MD, and Bruce Scali  Life Extension Magazine March 2015


References:

Zhang N, Song X, Zhang Y, et al. Alzheimer’s disease neuroimaging initiative— an MRI brain atrophy and lesion index to assess the progression of structural changes in Alzheimer’s disease, mild cognitive impairment, and normal aging: a follow-up study. J Alzheimers Dis . 2011;26 Suppl 3:359-67.

Cherubini A, Péran P, Spoletini I, et al. Combined volumetry and DTI in subcortical structures of mild cognitive impairment and Alzheimer’s disease patients. J Alzheimers Dis . 2010;19(4):1273-82.

Van Dinteren R, Arns M, Jongsma M. et al. P300 development across the lifespan: a systematic review and meta-analysis. PLoS One. 2014 Feb. 9(2):e87347.

Haeusler KG , Koch L, Herm J, et al. 3 Tesla MRI-detected brain lesions after pulmonary vein isolation for atrial fibrillation: results of the MACPAF study. J Cardiovasc Electrophysiol. 2013 Jan;24(1):14-21.

Wu Z , Mittal S,Kish K,Yu Y,Hu J, Haacke EM. Identification of calcification with MRI using susceptibility-weighted imaging: a case study. J Magn Reson Imaging. 2009 Jan;29(1):177-82.


Informational References:

For more detailed information on this subject, read the Life Extension article:  Reverse Mild Cognitive Impairment,  By Eric Braverman, MD, and Bruce Scali  Life Extension Magazine March 2015


The Potent Compounds of Salvia militorrhiza (Danshen)

Salvia miltiorrhiza, also known as red sage, Chinese sage, tan shen, or danshen, is a perennial plant in the genus SalviaSalvia miltiorrhiza is native to China and Japan where it grows at 90 to 1,200 m (300 to 3,940 ft) elevation, preferring grassy places in forests, hillsides, and along stream banks. The specific epithet miltiorrhiza means “red ochre root” as can be seen in the photo below:

DanshenRoot

Salvia militorrhiza BUNGE (Danshen) roots

Scientist have identified over 80 compounds in Danshen, both water soluble and fat soluble:  1  2  3

  • 50 water soluble compounds
    • Salvianolic acid B
    • Danshensu (Salvianolic acid A)
    • Protocatechuic aldehyde
  • 30 fat soluble compounds
    • Tanshinones
      • Tanshinone I
      • Tanshinone IIA 
      • Cryptotanshinone

The two compounds that show the most pharmalogical significance is the Salvianolic acids, Salvianolic acid A (danshensu) and the tanshinones, Tanshinone I and Tashinone IIA.

Salvianolic acid B is a potent antioxidant and has been investigated for its ability to protect against cerebrovascular disorders.  4  5

The Tanshinones (Dihydrotanshinone, tanshinone I, and tanshinone IIA) are currently being investigated for their anti-cancer effects.  6  7

The Table below lists the active compounds that have been studied for their therapeutic benefits in human health with references to various scientific studies for each compound:

Active Compounds in Salvia miltorrhiza Bunge

Compounds in Salvia miltorrhiza Bunge Clinical ApplicationsFunctions and UsesReferences
Cryptotanshinone1. Coronary heart disease and sugar diabetes; 2. Anti-infections; 3. To treat hepatitis and lepra disease.Cryptotanshinone is a major tanshinone isolated from Salvia miltiorrhiza that uses in many different fields. It has a good effection cardiovascular disease resisting fungus, also been effective to inhibit bacterium and diminish inflammation.1 2 3
Danshensu sodium1. Anti-bacterial 2. Anti-atherosclerotic 3. Enhancing immune1. Prevention for cardiac muscle, inhibit platelet aggregation; 2. Prevention for nerve cell and hepatic fibrosis; 3. Anti-bacterial, anti-inflammatory, anti-atherosclerotic and anticoagulation. Hypolipidemic effect and enhancing immune1 2 3
Danshensu/Salvianic Acid A1. Coronary heart disease 2. Anti-platelet aggregation 3. Protection for heartDanshensu is mainly used as raw material for clearing heat, anti-inflammation, detumescence and increasing coronary flow.1 2 3
Dihydroanshinone1. Antibacterium 2. Antifungal activity 3. Anti-thromboticSome inhibitory effects on Staphylococcus aureus, human-type Mycobacterium tuberculosis, Mycobacterium, leather bacteria etc. Inhibit platelet aggregation, anti-oxidants and expansion of coronary activity. Applied in medicine, healthcare food, food additive1 2 3 4 5 6
Magnesium Lithospermate B1. Anti-oxidative junction 2. Protection for heart 3. Protection for brain 4. Prevention for hepatic fibrosis 5. Anti-aging and anti-tumorPromoting blood circulation and removing blood stasis, Stimulate the menstrual flow and activate the collaterals. It is used for apoplexy and the angina caused by coronary artery disease. Anti-fibrosis of liver. Mainly applied in Medicine, healthcare food, food additive.1 2 3 4 5 6 7 8
Protocatechuic aldehyde1. Anti-inflammation 2. anti-prostaglandin 3. anti-lipid peroxidationIt has a strong effect on antithrombotic, improving the blood circulation and anti-oxidant. Applied in medicine, healthcare food, food additive.1 2 3 4
Salvianolic Acid B1. Anti-oxidative junction 2. Protection for heart 3. Protection for brain 4. Prevention for hepatic fibrosis 5. Anti-aging and anti-tumorPromoting blood circulation and removing blood stasis, Stimulate the menstrual flow and activate the collaterals. It is used to cure apoplexy and the angina caused by coronary artery disease. Anti-fibrosis of liver. Mainly applied in Medicine, healthcare food, food additive.1 2 3 4 5 6 7 8
Sodium tanshinoneⅡA sulfonate1. To ease postpartum pain 2.To remove goreSodium tanshinoneⅡA sulfonate is used to remove blood stasis and relieve pain, promote the flow of blood and stimulate menstrual discharge, expand blood vessels. It has a good effect on abnormal menstruation.1 2 3 4 5 6
Tanshinone I1. To depress pains in bodies 2. Promote the secretion of estrogen 3. Against angina pectoris1.It has a strong inhibition on human strains of Mycobacterium and is for the treatment of acne, and angina pectoris; 2. It is effective on the treatment of hepatitis and lepra disease. Applied in medicine, healthcare food, food additive.1 2 3 4 5 6 7 8
Tanshinone IIA1. To expend vessel 2. Depress blood pressure 3. Anti-thrombotic 4 AntioxidantUsed in medicine, healthcare food, food additive.1 2 3 4 5 6 7 8
Source of Columns 1, 2 and 3 is Xi 'an Honson Biotechnology Co., Ltd.
References provided by BioFoundations.org

 


Polypodium leucotomos may reduce the overproduction of Interleukin 6 (IL-6) by up to 100%

Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine.   1   The function of IL-6 is beyond the scope of this article.  Instead, the focus here is the excessive production of IL-6 and its implication in a variety of inflammatory disorders.   2

IL-6 stimulates the inflammatory and auto-immune processes in many diseases such as

  • Alzheimer’s Disease  3
  • Atherosclerosis  4
  • Behçet’s disease  5
  • Depression  6
  • Diabetes  7
  • Multiple myeloma  8
  • Prostate cancer  9
  • Rheumatoid arthritis  10
  • Systemic lupus erythematosus  11

A study published in the May-June 2000 edition of the Journal Anticancer Research, entitled, An extract of the fern Polypodium leucotomos (Difur) modulates Th1/Th2 cytokines balance in vitro and appears to exhibit anti-angiogenic activities in vivo: pathogenic relationships and therapeutic implications, showed that an extract of the fern Polypodium leucotomos (PLE) to partially inhibit the production of cytokines showing a Th1 pattern (IL-2, IFN-gamma and TNF-alpha) in human PHA-stimulated peripheral blood mononuclear cells.  12

The authors were surprised to find:

“that the production of the inflammatory cytokine IL-6 was completely abolished (100% inhibition) by PLE at all doses tested.”  13

Polypodium leucotomos is also known as and is an epiphytic fern native to tropical and subtropical regions of the Americas.  An extract of Polypodium leucotomos called Fernblock has proven photoimmunoprotection  properties with oral and topical application.

The extract has extensive preclinical and clinical data supporting its safety and efficacy in protecting against damage caused by solar radiation, and preventing and treating sun-related disorder.  14  15


Informational References:

Industrial Farmaceutica Cantabria. S.A. – Fernblock®


Resources:

Polypodium Leucotomos Extract 240mg ~ 200 Capsules – No Additives ~ Naturetition Supplements

Polypodium Leucotomos Extract 240mg * 200 Capsules 100 % Natural – by EarhNaturalSupplements

Shade Factor


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Oxaloacetate Reduces Neuroinflammation

Neuroinflammation is inflammation of the brain and nervous tissue. The common causes of chronic neuroinflammation include:

  • Aging
  • Air pollution
  • Autoimmunity
  • Microbes
  • Passive smoke
  • Toxic metabolites
  • Traumatic brain injury
  • Viruses

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls:

  • cell survival
  • cytokine production
  • transcription of DNA

NF-kB is an important factor in the inflammation pathway and if there is excessive or overly activated NF-kB, then this reaction can result in chronic inflammation not only in the nervous tissue but throughout the body.

NF-κB is involved in cellular responses to stimuli such as:

  • bacterial or viral antigens
  • cocaine
  • cytokines
  • free radicals
  • isoproterenol
  • oxidized LDL
  • stress
  • ultraviolet irradiation
  • tumor necrosis factor alpha (TNFα),
  • interleukin 1-beta (IL-1β)

NF-κB has been shown to have diverse functions in the nervous system.  Activated NF-κB can be transported retrogradely from activated synapses to the nucleus to translate short-term processes to long-term changes such as axon growth, which is important for long-term memory. 1

In glia, NF-κB is inducible and regulates inflammatory processes that exacerbate diseases such as autoimmune encephalomyelitis, ischemia, and Alzheimer’s disease. In summary, inhibition of NF-κB in glia might ameliorate disease. 2

NF-KBPathway

Abating or lowering the NF-kB protein trans-location to the nucleus when inflammation is present is one of the strategies to reducing neuroinflammation and chronic inflammation in general.

A study from December 2014 published in the Journal Human Molecular Genetics, entitled “Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis”, found among other things, that oxaloacetate reduces neuroinflammation.

Oxaloacetic acid (also known as oxalacetic acid or oxaloacetate ) is a metabolic intermediate in many processes that occur in humans and other animals. Oxaloacetate takes part in many systems within the body, such as:

  • amino acid synthesis
  • citric acid cycle
  • fatty acid synthesis
  • gluconeogenesis
  • glyoxylate cycle
  • urea cycle
Oxaloacetic_acid

Oxaloacetic acid molecule

In the December 2014 study, the researchers assessed the effects of Oxaloacetate (OAA) administration on brain inflammation.  They measured the mRNA levels for two inflammation-related genes, tumor necrosis factor α (TNFα) and C–C motif chemokine 11 (CCL11).

While hippocampal TNFα levels were comparable across the groups, hippocampal CCL11 mRNA levels were 44% lower in the group receiving 2 g/kg/day than they were in the control group (Figure 1).

The amount of nuclear factor κB (NFκB) protein was lower in the nucleus of the combined OAA treatment group (by 50%), after two weeks of OAA supplementation, and in both OAA treatment groups the nucleus-to-cytoplasm ratio was ∼70% lower than it was in the control group.  3 

 

An external file that holds a picture, illustration, etc. Object name is ddu37105.jpg

Figure 1:  Effect on inflammation. (A) TNFα mRNA levels were comparable. (B) CCL11 mRNA was lower in the 2 g/kg/day OAA group. (C) Nuclear NFκB protein was lower in the combined OAA group. Although the ANOVA was not significant, on post hoc analysis nuclear NFκB protein was lower in the 1 g/kg/day OAA group. (D) The NFκB nucleus:cytoplasm ratio was lower in the 1 g/kg/day, 2 g/kg/day and combined OAA groups. Values shown are relative group means ± SEM. *P < 0.05; **P < 0.005; #ANOVA comparison was not significant, but the post hoc LSD test between the specified treatment group and the control group was significant at P < 0.05.  (Source:  Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis, Hum Mol Genet. 2014 Dec 15; 23(24): 6528–6541. Published online 2014 Jul 15. doi:  10.1093/hmg/ddu371)

The researchers concluded that:

When activated, NFκB’s restraint is removed and it moves to the nucleus. Since NFκB promotes the CCL11 gene, reduced NFκB may account for lower CCL11 expression. OAA, therefore, could prove useful for treating brain diseases in which neuroinflammation occurs.”  4


 

Resources:

benaGene by benaGene

Advanced Orthomolecular Research AOR Benagene Capsules, 30 Count

 


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Balancing Your Neurotransmitter Systems Naturally

A balanced and healthy nervous system requires a sufficient level of neurotransmitters. 

There are a number of neurotransmitters that have been identified and are typically classified as:

  • Amino acids
  • Monoamines
  • Peptides

Another classification of neurotransmitters is whether they are inhibitory or stimulatory.  For purposes of this article, four main neurotransmitters are examined:

  • Stimulatory
    • Acetylcholine
    • Dopamine
  • Inhibitory
    • GABA
    • Serotonin

The Table below lists the four major neurotransmitters and their certain characteristics:

Neurotransmitter Systems

SystemAcetylcholineDopamineGABASerotonin
SystemCholinergicCathecholamineGABAergicSerotonergic
TypeStimulatoryStimulatoryInhibitoryInhibitory
Lobe of the BrainParietal lobesFrontal lobesTemporal lobesOccipital lobes
BrainwaveAlphaBetaThetaDelta
Brain MeasurementSpeedVoltageBalance (Calm)Synchrony (Rest)
CharacteristicsLubricant to neuronsPowerCalmnessHealing
BalancedCreativeBlood pressureStabilityNourishment
Fast thinkingMetabolismEven moodSatisfied feelings
Feelings of wellbeingDigestionMake good decisionsSleep deeply
Voluntary movementThink rationally
Intelligence
Abstract thought
Goal setting
Long term planning
CharacteristicDecreased brain speedDecreased brain powerHeadachesDepression
DeficiencyBrain fogFatiguePalpitationsSleep disorders
DementiaAddictionSeizuresEating disorders
AlzheimersLoss of attentionAnxietySensory processing
dysfunction
Dietcholine-rich: almonds; artichokes; lean beef; broccoli; Brussels sprouts; cabbage; fish; pine nuts; tomato paste; wheat bran; toasted wheat germ.high-protein: meat, poultry, cottage cheese, wheat germ; eggs; yogurt; walnuts; dark complex carbohydrates: Brown rice; broccoli; lentils; almonds; bananas; whole grain oats; oranges; spinach; walnuts; whole grain wheat..tryptophan-rich: turkey; chicken; sausage; avocados; cheese; cottage cheese; ricotta; eggs; granola; oat flakes; luncheon meats; wheat germ; whole milk; yogurt.
Supplementsphospatidylcholine powder; choline powder; huperzine A; phosphatidylserine; dopa bean; Ginkgo biloba; piracetam; omega-3 fish oil; pregnenolone. Phenylalanine; tyrosine; methionine; rhodiola; pyroxidine; B complex; DHEA; phosphatidylserine; Ginkgo biloba; green tea extract. Inositol powder; thiamine; tryptophan; passionflower; melatonin; magnesium; glutamic acid; niacinamide; pyridoxine; valerian root.tryptophan; calcium; fish oil; 5-HTP; magnesium; melatonin; passionflower; pyridoxine; SAM-e; St. John’s Wort; zinc.

To achieve a healthy nervous system, the stimulatory and inhibitory neurotransmitters should be balanced as much as possible.  Sometime this is not as easy as it sounds.  However, it is important to achieve a synergistic energy between the stimulatory and inhibitory neurotransmitters in which they work together to create balance in the nervous system.

An imbalanced neurotransmitter system can be characterized by a low level of all four neurotransmitters or a low level of a few neurotransmitters and an excess of other neurotransmitters.  Neurotransmitter imbalances can lead to a number of symptoms and pathologies.  Such imbalances are linked to:

  • ADD/ADHD
  • Addiction or dependency
  • Adrenal dysfunction
  • Anxiety
  • Compulsive behavior
  • Cravings
  • Depression
  • Fatigue
  • Insomnia
  • Loss of appetite control
  • Loss of mental focus, or cognitive fog
  • Low libido
  • Migraines
  • Obsessive Compulsive Disorder
  • Poor sleep
  • Sexual dysfunction
  • Weight Issues

The cause of neurotransmitter imbalances can be defined by many different factors, including:

  • Alcohol
  • Caffeine usage
  • Dietary deficiencies
  • Digestive imbalances
  • Drug use (prescription and recreational)
  • Food intolerances
  • Genetic predisposition
  • Medication use, including antidepressants, anti-anxiety, sleep and migraine medications
  • Neurotoxins
  • Poor eating habits
  • Sleep disturbances
  • Stress
  • Toxic burden

Stress is often times the primary contributor to neurotransmitter imbalance. The nervous system uses up large amounts of neurotransmitters in order to cope with the ongoing stress.

A number of tests have been developed that may determine what neurotransmitters are low or imbalanced:

Dr. Braverman, M.D. of Path Medical in New York City has designed two interesting tests that can be taken quickly to determine your neurotransmitter dominance and neurotransmitter deficiency:

Another test is offered by Integrative Psychiatry and is used to determine neurotransmitter deficiency:

In addition to the written tests to determine neurotransmitter deficiencies, there are also medical lab tests that can be prescribed by a health care professional.  These medical tests include:


For a more in-depth analysis of each of the four neurotransmitters and how to enhance these neurotransmitters and create a balanced nervous system, please read the following articles below:

Acetylcholine

Dopamine

GABA

Serotonin


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Maintaining the Integrity of the Blood-Brain Barrier

The blood–brain barrier (BBB) is a highly selective permeability barrier that separates the circulating blood from the brain extracellular fluid (BECF) in the central nervous system (CNS). The blood–brain barrier is formed by capillary endothelial cells, which are connected by tight junctions with an extremely high electrical resistivity.

The BBB is distinct from the quite similar blood–cerebrospinal-fluid barrier, which is a function of the choroidal cells of the choroid plexus, and from the blood–retinal barrier, which can be considered a part of the whole realm of such barriers.

The BBB has several important functions:

  • Protects the brain from “foreign substances” in the blood that may injure the brain
  • Protects the brain from hormones and neurotransmitters in the rest of the body
  • Maintains a constant environment for the brain

The general properties of the BBB include:

  • Large molecules do not pass through the BBB easily
  • Low lipid (fat) soluble molecules do not penetrate into the brain. However, lipid soluble molecules, such as barbituate drugs, rapidly cross through into the brain
  • Molecules that have a high electrical charge are slowed

The BBB can be broken down (permeated) by:

  • Hypertension (high blood pressure): high blood pressure opens the BBB.
  • Hyperosmolitity: a high concentration of a substance in the blood can open the BBB.
  • Microwaves: exposure to microwaves can open the BBB.
  • Radiation: exposure to radiation can open the BBB.
  • Infection: exposure to infectious agents can open the BBB.
  • Trauma, Ischemia, Inflammation, Pressure: injury to the brain can open the BBB.

Through extensive study, scientists have found that compounds that are very small and/or fat-soluble, including antidepressants, anti-anxiety medications, alcohol, cocaine, and many hormones are able to slip through the endothelial cells that make up the blood-brain barrier without much effort. In contrast, larger molecules, such as glucose or insulin, must be ferried across by proteins. These transporter proteins, located in the brain’s blood vessel walls, selectively snag and pull the desired molecules from the blood into the brain.

When the blood-brain barrier breaks down, as is the case in some brain cancers and brain infections or when tiny ruptures to blood vessels occur, some substances that are normally kept out of the brain gain entry and cause problems for the brain.

Mercury penetrates the blood-brain barrier around the brain, and as little as one part per million can impair this barrier, permitting entry of substances in the blood that would otherwise be excluded.  1

There are a number of natural substances that can be consumed to maintain the integrity of and enhance the blood-brain barrier.  These natural substances are listed in the Table below:

Natural Substances that Maintain the Integrity of and Enhance the Blood-Brain Barrier

CategoryNatural SubstanceReferences
Foods
Bilberry1
Herbs
Ginko Biloba2
Hormones
Progesterone3
Polyphenols
Anthocyanins (Plants rich in anthocyanins are Vaccinium species, such as blueberry, cranberry, and bilberry; Rubus berries, including black raspberry, red raspberry, and blackberry; blackcurrant, cherry, eggplant peel, black rice, Concord grape, muscadine grape, red cabbage, and violet petals. Red-fleshed peaches and apples contain anthocyanins.)4 5
Curcumin6
Vitamins
Vitamin B1 (Vitamin B1 deficiency can lead to break down of BBB)7 8


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Amino Acid Conjugation Pathway in Metabolic Detoxification: Glycine is the Main Amino Acid

Phase 1 Biotransformation Process

The primary function of the Phase I biotransformation process is to either:

  • Biotransform a toxic lipophilic compound directly to a more hydrophilic compound so it can be directly excreted in the kidneys (e.g. caffeine). Though, Phase I usually results in only a small amount of direct hydrophilicity and excretion
  • The bulk of Phase I enzymatic activity takes place in the form of altering unwanted compounds in a way as to either expose or introduce a functional group. Functional groups such as: Carboxyl group (–COOH), hydroxyl group (– OH), amino group (-NH2), or sulfhydryl group/thiol (-SH)

In the Phase 1 detoxification process a toxic chemical is converted into a less harmful chemical through various chemical reactions.  Phase 1 is essentially responsible for breaking fat-soluble toxins down and then sending the raw materials to Phase 2 detoxification process.  Phase 2 is the addition or conjugation phase where new substances are added/conjugated to the toxic metabolites produced in Phase 1 in order to make them easier to transport, more stable and/or more functional for the body.

Phase 2 Conjugation Pathways

There are 6 Conjugation Pathways in the human body and they include:

  • Sulphation (sulfation) pathway
  • Glucoronidation pathway
  • Glutathione conjugation pathway
  • Acetylation pathway
  • Methylation (& Sulfoxidation) pathway
  • Amino Acid conjugation pathway (glycine, cysteine, glutamine, methionine, taurine, glutamic acid and aspartic acid)

These 6 conjugation pathways occur in different organs of the body.  The locations of the Phase 2 conjugation pathways are listed in Table 1.

  Table 1 Locations of Phase 2 Conjugation Systems

Conjugation System

Location in Body

Glycine conjugation

liver, kidney

Glutathione conjugation

liver, kidney

Glucuronidation

liver, kidney, intestine, lung, skin, prostate, brain

Acetylation

liver, lung, spleen, gastric mucosa, RBCs, lymphocytes

Sulphation

liver, kidney, intestine

Methylation

liver, kidney, lung, CNS

(Source:   Liston HL, Markowitz JS, DeVane CL (October 2001). “Drug glucuronidation in clinical psychopharmacology”. J Clin Psychopharmacol 21 (5): 500–15.)

Amino Acid Conjugation Pathway

The Amino Acid conjugation pathway is less utilized by the body, yet is still a very important conjugation pathway. 

The conjugation of toxins with amino acids occurs in this pathway. The amino acids commonly used in this pathway include:

  • Glycine
  • Taurine
  • Glutamine

but arginine, and ornithine are also used.

image

Figure 1:  Amino acid conjugation pathways

(Source:  Wikipathways)

The Amino Acid Conjugation Pathway often includes the Acylation Pathway.  Acylation uses acyl CO-A with the amino acids glycine, glutamine and taurine. Conjugation of bile acids in the liver with glycine or taurine is essential for the efficient removal of these potentially toxic compounds.  

The main amino acid in the Amino Acid Conjugation Pathway is glycine.  Glycine is the smallest of the 20 amino acids commonly found in proteins.  Glycine is a colorless, sweet-tasting crystalline solid. It is unique among the proteinogenic amino acids in that it is achiral. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom.

Since it plays such an important role in the Amino Acid Conjugation Pathway, it is also known as the Glycination Pathway.  Salicylates and benzoate are detoxified primarily through glycination. Benzoate is present in many food substances and is widely used as a food preservative.

In humans, there is a wide variation that exist in the activity of the glycine conjugation, which is primarily due not only to genetic variations, but also to the availability of glycine in the diet.

High-protein rich foods should be consumed in the diet to ensure that the amino acid conjugation is functioning properly.  There are a number of natural substances that induce the

Amino Acid Conjugation Pathway and act as co-factors in the conjugation process.  These substances are listed in Table 2. 

Table 2 Natural Substances that Induce the Amino Acid Conjugation Pathway

 

Category

Food

Minerals

 

 

Magnesium

 

Iron

Vitamin

 

 

B Complex Vitamins (particularly

Vitamin B3 and Vitamin B6)

Amino Acids

 

 

Glycine

 

Methionine

 

Taurine

 

Cysteine

 

Glutamine


Resources:

Life Extension – Glycine (Capsules)

NOW – Glycine (Powder)


Cover Photo Source:  Perfect Health Diet


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Cistanche deserticola May Extend Life Span (At Least in Mice)

Cistanche deserticola is a holoparasitic member of the Orobanchaceae family of plants.  It is primarily found in China’s deserts including the provinces of Gansu, Shaanxi, and Qinghai, and the Autonomous Regions of Xinjiang, Ningxia, and Inner Mongolia.

Cistanchedeserticola

Cistanche deserticola

Cistanche deserticola has been widely used in Traditional Chinese Medicine as the herbal medicine called Rou Cong Rong.

In China, it has been used in treating various age-related disorders, including:  1

  • Senile dementia,
  • Impotence
  • Infertility
  • Chronic infection
  • Hematopoietic disorders in the elderly

There are two principal types of compounds isolated as the main active ingredients of Cistanche deserticola:

  • Phenylethanoid glycosides
  • Oligosaccharides

Cistanche deserticola and its extracts have been studied intensively and have been shown to have the following health benefits:

  • Protecting neurons from injury induced by neurotoxins  2
  • Inhibiting carbon tetrachloride induced hepatotoxicity  3
  • Promoting the recovery of bone marrow cells from radiation damage  4
  • Anti-inflammatory, antioxidant, and antiaging effects  5

A group of Chinese researchers published a study on January 9, 2014 which demonstrated that Cistanche deserticola possesses significant effects in extending life span and suggest this is achieved by antagonizing immunosenescence.  6

Immunosenescence refers to the gradual deterioration of the immune system brought on by natural age advancement.  Immunosenescence creates the environment for increased susceptibility in the elderly to:  7

  • Infections
  • Cancer
  • Neurodegenerative diseases
  • Autoimmune diseases

In addition to an reduction in the level of immunity that is evident in aging (Immunosenescence), an increase in chronic inflammation is apparent in aging and manifested as increased levels of proinflammatory cytokines, including IL-6, TNF-α, and IL-1β.  8

The most damaging inflammatory cytokines is IL-6.  IL-6 increases with aging and age-related diseases.  9  10  11  As demonstrated in the study, supplementation with Cistanche deserticola was able to reduce peripheral IL-6 concentrations.  12 

The Chinese researchers took eight-month-old male SAM-P8 mice and treated them with oral administrations of Cistanche deserticola for 4 weeks. The researchers stated that:

“The results showed that dietary supplementation of 150 mg/kg and 450 mg/kg of Cistanche deserticola (ECD) could extend the life span measured by Kaplan-Meier survival analysis in dose-dependent manner. Dietary supplementation of SAM-P8 mice for 4 weeks with 100, 500, and 2500 mg/kg of ECD was shown to result in significant increases in both naive T and natural killer cells in blood and spleen cell populations. In contrast, peripheral memory T cells and proinflammatory cytokine, IL-6 in serum, were substantially decreased in the mice that ingested 100 and 500 mg/kg of ECD daily.”  13

The study revealed that the average life span was significantly increased (by 15.4%) in the Cistanche deserticola supplemented mice:  14

  • Control mice averaged about 325 days
  • Cistanche deserticola supplemented mice averaged about 375 days

601383_fig_001a

601383_fig_001b

Figure 1: The effects of extracts of Cistanche deserticola (ECD) on life span of SAM-P8 mice. Eight-month-old male senescence-accelerated mouse/prone 8 (SAM-P8) mice were randomly divided into 4 groups (in each group, ): 3 treatment groups, and a no treatment control group. The nonsenescent substrain (SAM-R1) of mice was used as an experimental control. The food intake of all of animals was monitored throughout the experiment at 3-day intervals. The 3 treatment groups were fed ad libitum on diets supplemented with low (50 mg/kg), medium (150 mg/kg), and high (450 mg/kg) doses of Cistanche deserticola extract (ECD). The two control animal groups were fed with the same diet without ECD supplementation. (a) Kaplan-Meier survival curves of SAM-P8 mice dieted ECD or vehicle control. The Kaplan-Meier survival analysis was conducted using the Log-rank (Mantel-Cox) and Gehan-Breslow-Wilcoxon tests. (b) Histogram of the average life span of the groups of mice. The error bars show that the standard deviation from the mean and statistical significance was carried out using ANOVA analysis followed by post hoc -test. SAM-P8 versus SAM-R1; high dose treated group versus SAM-P8; medium dose treated group versus SAM-P8 (in each group, ).  (Source:  Extracts of Cistanche deserticola Can Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8 (SAM-P8) Mice, Evidence-Based Complementary and Alternative Medicine Volume 2014 (2014), Article ID 601383, 14 pages)

The results and conclusion of the study found the following promising health benefits of Cistanche destericola:  15

  • Induced a significant reversal of age-related immunosenescence alterations
  • Reduction in peripheral and spleen cell populations of naive T cells and NK cells
  • Reduction in redundant memory T cells
  • Suppression of necrosis in peripheral lymphocytes
  • Suppression of the proinflammatory cytokine, IL-6
  • Prolonged the life span of senile SAM-P8 mice

Resources:

Life Extension Standardized Cistanche Capsules, 30 Count

Swanson Health Products – Cistanche Tubulosa Extract

Life Extension – Immune Senescence Protection Formula™

Rou Cong Rong


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Vitamin D Deficiency is Associated with a Substantially Increased Risk of All-Cause Dementia and Alzheimer Disease

Vitamin D refers to a group of fat-soluble secosteroids (pro-hormones) responsible for increasing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc, among other multiple functions.

For human therapeutic purposes, there are two important compounds in the vitamin D group:

  • Vitamin D2 (also known as ergocalciferol)
  • Vitamin D3 (also known as cholecalciferol)
Image result for cholecalciferol ergocalciferol

Vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease

A  number of research studies have indicated that low levels of 25-hydroxyvitamin D is associated with the development of dementia and ultimately Alzheimer’s disease.

In a study from October 2014, epidemiological evidence strongly suggests that circulatory levels of 25-hydroxyvitamin D below 50 nmol/l are associated with cognitive impairment and the development of dementia.  1    

Image result for vitamin d alzheimers

Figure 1. Circulatory levels of 25-hydroxyvitamin D below 50 nmol/l are associated with cognitive impairment and the development of dementia   (Source)

In another study from August 2014, researchers sought to determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. 

One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population–based Cardiovascular Health Study between 1992–1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992–1993.

During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease.

Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23–4.13) and 1.53 (95% CI: 1.06–2.21) compared to participants with sufficient concentrations (≥50 nmol/L).

The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02–4.83) and 1.69 (95% CI: 1.06–2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

Researchers confirmed that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.  2

171 participants developed all-cause dementia

102 participants developed Alzheimer disease

The risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

In a study from May 2014, researchers hypothesized that reduced plasma 25-hydroxyvitamin D (25[OH]D) is associated with increased risk of Alzheimer’s disease (AD) and vascular dementia in the general population.  They measured baseline plasma 25(OH)D in 10,186 white individuals from the Danish general population.

During 30 years of follow-up, 418 participants developed AD and 92 developed vascular dementia. Multivariable adjusted hazard ratios for AD were 1.25 (95% confidence interval [CI], 0.95-1.64) for 25(OH)D less than 25 nmol/L vs. greater than or equal to 50 nmol/L, and 1.29 (95% CI, 1.01-1.66) for less than the 25th seasonally adjusted 25(OH)D percentile vs. more than the 50th seasonally adjusted 25(OH)D percentile. Multivariable adjusted hazard ratios for vascular dementia were 1.22 (95% CI, 0.77-1.91) for 25(OH)D less than 50 nmol/L vs. greater than or equal to 50 nmol/L, and 1.22 (95% CI, 0.79-1.87) for less than or equal to the 50th vs. more than the 50th seasonally adjusted 25(OH)D percentile.

Researchers observed an association of reduced plasma 25(OH)D with increased risk of the combined end point of AD and vascular dementia in this prospective cohort study of the general population.  3

418 participants developed Alzheimer disease

92 participants developed vascular dementia

The risk of vascular dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

Testing for Vitamin D levels in Blood Serum

Vitamin D levels in the blood serum can be tested with a blood draw test.  Both forms of vitamin D can be tested.  The names of the tests are:

  • 25-hydroxyvitamin D3 (cholecalciferol)
  • 25-hydroxyvitamin D2 (ergocalciferol)

The Vitamin D Council has written about the various levels of 25(OH)D and their recommendations of how much vitamin D3 to supplement to raise it to safe levels.

Image result for vitamin d council vitamin d levels

The Vitamin D Council suggests that a level above 50 ng/ml and below 80 ng/ml is the ideal level to aim for. This is why the Council recommends that adults take 5,000 IU/day of vitamin D supplement in order to reach and stay at this level.

Foods that Contain Vitamin D2 and Vitamin D3

There are a limited number of foods that contain vitamin D2 and vitamin D3.  There are more of a variety of foods that contain vitamin D3 than vitamin D2.  Of all the foods that contain vitamin D2 and D3, none of them have high quantities, with maybe cod liver oil as the exception.

Because there are limited amounts of foods that contain vitamins D2 and D3, it is necessary to supplement with vitamin D3 to reach the acceptable levels of 25-OH-D.

Vitamin D2

Very few foods contain Vitamin D2:

All of the above listed foods contain less than 600 IU’s per 100 grams.

Vitamin D3

Most vitamin D3 found in food is from animal sources (fish, eggs, beef):

  • Lichen (Cladina arbuscula)
  • Cod liver oil (4.5 g (1 teaspoon) provides 450 IU (100 IU/g))
  • Salmon
  • Mackerel
  • Tuna
  • Sardines  (canned in oil)
  • Egg yolk  (cooked)
  • Beef liver  (cooked, braised)

Other than cod liver oil, all other foods that contain vitamin D3 contain less than 600 IU’s per 100 grams.

Very few foods contain vitamin D so the synthesis of vitamin D (specifically cholecalciferol) is through the skin. Dermal synthesis of vitamin D from cholesterol is dependent on sun exposure (specifically UVB radiation).  

Informational References:

Vitamin D Council

Vitamin D Day  

Nattokinase May Be Effective in Breaking Down Toxic Amyloid Fibrils in Alzheimer’s Disease

Nattokinase is an serine proteinase enzyme extracted and purified from the Japanese food called nattō. 1  Nattō is produced by taking boiled soybeans and fermenting them with the bacterium Bacillus subtilis var. natto.  

Image result for nattokinase

Figure 1.  Natto

Nattokinase is produced by the bacterium acting on the soybeans.

Figure 2.  Crystal structure of nattokinase from Bacillus subtilis natto.  (Source)

Nattokinase exhibits a strong fibrinolytic (fibrinolysis) activity.  2  Fibrinolysis is a process that prevents blood clots from growing and becoming problematic.  In the process of fibrinolysis, a fibrin clot, which is the product of coagulation, is broken down and then cleared by the kidneys and liver.

A research study from 2009 and published in the Journal of Agriculture and Food Chemistry showed that nattokinase may be effective in breaking down toxic amyloid fibrils associated with Alzheimer’s disease.   3 

The study’s authors noted that

“[t]his amyloid-degrading ability of nattokinase suggests that it may be useful in the treatment of amyloid-related diseases,” particularly as “[p]revious results in rats, dogs and humans have suggested that nattokinase can enter the circulation when taken orally.”

Abstract Image

Figure 3.  Nattokinase breaking amyloid fibrils  (Source)

The authors cautioned that their results were preliminary, and made the following suggestion:

“[S]ince natto has been ingested by humans for a long time, it would be worthwhile to carry out an epidemiological study on the rate of occurrence of various amyloid-related diseases in a population regularly consuming natto.”