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The Nutrition InvestigatorThe health and nutrition blog by Dr. Roc Ordman.

A supplement to extend healthspan and maintain a healthier brain

by Roc (click here for full post)

By Alfred “Roc” Ordman

ABSTRACT

  AARP magazine has stated that brain supplements do not work. I report here on a supplement designed based on peer-reviewed scientific journal reports of biochemical mechanisms and epidemiological studies which justify a formulation likely to prevent protein misfolding (PM).  PM is one of the major causes contributing to brain disorders like Alzheimer’s and Parkinson’s.  When mRNA is translated too rapidly, it produces protein clumps that contribute to senescent cells.  There are a variety of new nutrients with defined actions that will contribute to a longer healthspan for our aging population. This article provides citations and explanations of the rapid progress to new ways to maintain health as we age. This formulation is being produced by MDR, with the brandname Mito-C, for a healthy mind and body.

INTRODUCTION

   On June 11, 2019 AARP magazine had an article stating that brain supplements do not work.  Here I describe Mito-C, a supplement designed to address serious concerns particularly for our aging brains, and how each ingredient addresses them.  In peer-reviewed scientific publications, these ingredients are also reported to reduce other age-related declines and diseases. 

   Research has shown that caloric restriction (CR) substantially lengthens the lives of animals, and reduces the rate of age-associated diseases, extending life 600% in C. elegans. CR involves maintaining all essential nutrients in the diet, while reducing caloric intake substantially.  Even 12 hours of fasting on a regular basis has been shown to improve the health of humans. Recently a biochemical mechanism for this has been identified [Hahm 2019].  It involves inhibition of translation, so that proteins are properly synthesized from mRNA.  This indicates that a process which can reduce protein misfolding will slow decline from aging. 

   A major recent unifying theme in research about why we age is the protein misfolding theory of aging [Kikis 2010, SENS 2009]. The basic concept is that as we age, our bodies synthesize proteins too rapidly. Because of insufficient time to find the proper amino acids during translation or enough time during synthesis for them to fold into the proper shape to function correctly, our cells make dysfunctional proteins. When we are young, these are degraded by proteasomes [Tanaka 2009].  But as we age, they accumulate more quickly, clump together, and form globs too large for the proteasomes to degrade.  This leads to mitochondria unable to produce energy, senescent cells that persist and produce harmful signals, and plaque consisting of dysfunctional proteins.  In the general circulatory system, plaque consisting of macrophages bloated from consuming oxidized low-density lipoproteins (ox-LDL) contributes to heart disease.  In the brain, both forms of plaque contribute to memory loss, Alzheimer’s, Parkinson’s, and other dementias [NIH 2019]. So reducing both forms of plaque from PM and from ox-LDL is likely to increase healthspan of the body and brain significantly.

COMPOSITION AND JUSTIFICATION

  To reduce the amount of protein misfolding, I have developed a nutritional supplement, to be produced by MDR Fitness Corp (Sunrise, FL USA), to be marketed as Mito-C, for healthy mind and body.  The composition is shown in Table 1.  For the other form of plaque caused by ox-LDL, it contains additional ingredients to reduce the production of free radicals.

Based on the work of Ordman [King 1994], the level of vitamin C in the tablet will maintain near its highest concentration in people’s blood. It is assumed one is taking another supplement containing vitamin C to achieve a total dosage of 500 mg twice a day, such as another MDR Supplement, AM/PM Fitness Tabs. There are numerous likely benefits. A major cause of plaque in the arteries and the brain is oxidized low-density lipoprotein (ox-LDL). When free radicals are generated in the blood, if there is inadequate vitamin C to maintain the reduction of LDL, ox-LDL is formed.  Macrophages recognize this as a foreign molecule, consume it, and turn into foam cells. It is these cells that are sticky, attach to the circulatory system, for instance in small capillaries in the brain, and produce plaque [NIH 2019]. Besides heart disease, this plaque can contribute both to major and mini-strokes, harming brain function.  Another molecule that traps free radicals is glutathione, often called the body’s master antioxidant. It also provides cysteine to help prevent protein misfolding, as described below.

        The levels of quercetin and EGCG (Epigallocatechin gallate) are based on peer-reviewed articles about their functions to maintain health as we age.  Quercetin blocks the action of the enzyme responsible for degrading EGCG, which is the active ingredient in green tea [Wang 2012]. Servings of green tea consumed daily have been shown to be correlated with health [Blumberg 2012]. By combining quercetin with the amount of EGCG in a single cup of tea, our supplement provides the benefit equal to the exposure from six cups. This reduces protein misfolding and activates the beneficial processes similar to those of dietary restriction.  

Alpha-lipoic acid (ALA), N-acetyl-carnitine (NAC)  and niacinamide are nutrients known to diminish with age [Ames 2009].  All three are vital to brain function and energy.  NAC transports fatty acids into the mitochondrion, and ALA aids their degradation to generate energy. NAD+ levels diminish with age and are replenished by supplemental niacinamide [Johnson 2018].

Bioflavonoids, including quercetin, have numerous health benefits. It was recently discovered that one bioflavonoid, apigenin, especially high in parsley, inhibits CD 38, also known as cyclic ADP ribose hydrolase, a glycoprotein found on the surface of many immune cells and the main reducer of NAD+ concentration during aging [Escande 2013]. These ingredients help restore NAD+ toward more youthful levels.

Deficiency of the amino acids tyrosine and cysteine contributes to protein misfolding during transcription. Many diets are deficient in these 2 amino acids, and people in regions of the world where people live longest have higher levels of these 2 amino acids in their diets.  In addition, EGCG slows the transcription process so proteins can fold properly.  These findings are based on work with Rolf Martin [Chaudhuri 2009]. Protein misfolding contributes to Alzheimer’s, Parkinson’s, and other age-associated diseases [Darnell 2014] 

When Vitamin K is consumed at levels above the daily value, it has been shown by metabolomic analysis to activate a variety of decalcifying enzymes, removing calcium where it is hazardous as we age and maintaining it where it is needed.  This may have numerous health benefits.  You are less likely to break a hip. You are more likely to maintain a stronger bone mass. You will reduce your risk for Alzheimer’s and Parkinson’s diseases. You may maintain a healthier blood pressure and have a better cardiac rhythm. Many of these effects occur because K-induced enzymes decalcify soft tissues where excess calcium causes harm [Maresz 2015].

Finally, the supplement contains parsley leaf. Parsley is a rich source of apigenin, but also has been praised as a dietary source of many other benefits. “[A] wide range of pharmacological activity including antioxidant, hepatoprotective, brain protective, anti-diabetic, analgesic, spasmolytic, immunosuppressant, anti-platelet, gastroprotective, cytoprotective, laxative, estrogenic, diuretic, hypotensive, antibacterial and antifungal activities have been exhibited for this plant in modern medicine.” [Allam 2016, Farazei 2013]

DISCUSSION

   The number of scientists alive today is greater than all who have lived previously.  The level of medical knowledge is projected to double every 7 months by 2020.  Because of an abundance of deceptive products and claims, we are not effectively informed of the great increase in knowledge of the benefits of proper nutrition.

   As an example, in 2019 the pathway by which dietary restriction [DR] slows the aging process was discovered [Hahm 2019].  DR slows the process by altering a signal so that proteins are synthesized more slowly, reducing the rate of protein misfolding described above. Thus, consuming quercetin and EGCG has an effect similar to DR, without the need to fast for 12 hr or longer.  The formula for Mito-C is thus likely, based on peer-reviewed published scientific mechanisms, to slow the rate of declining health associated with aging, particularly by maintaining a healthier brain.

   The formulation in this supplement reflects current knowledge of safe and inexpensive nutritional supplements likely to maintain the health of our brains and reduce the risk of diseases associated with aging.  As additional research provides further advances, the product will be reformulated to maintain its basis for optimal health.

TABLE 1: Ingredients in Mito-C: Supplement for a healthy body and brain

250 mg Vitamin C 

75 mcg Vitamin K 

25 mg alpha-lipoic acid – Based on Ame’s research (2009)

25 mg N-acetyl-carnitine – Based on Ame’s research (2009)

  5 mg niacinamide – We lose NAD+ as we age, and need niacinamide to keep our mitochondrial levels up (Darnell 2014)

25 mg quercetin– The amount in 5 cups blueberries 

40 mg EGCG– The amount in 1 cup of green tea

25 mg tyrosine – Needed for correct protein synthesis 

25 mg Glutathione – One of the body’s most powerful antioxidants, it also detoxifies xenobiotics and provides cysteine for correct protein synthesis

25 mg bioflavonoids and 15 mg Parsley leaf – Rich sources for the flavonoid apigenin [Escande 2013]

REFERENCES

Allam AA et al 2016 Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain. Oxid Med Cell Longev 2016: 2646840. PMCID: PMC4761399 PMID: 26966507

Ames BN 2009 Mitochondrial Decay in the Brains of Old Rats: Ameliorating Effect of Alpha-Lipoic Acid and Acetyl-L-carnitine. Neurochem Res. 34: 755–763

Blumberg J 2012 Proceedings of the Fifth International Scientific Symposium on Tea and Human Health. USDA

Chaudhuri TK, Paul S 2009 Protein-misfolding diseases and chaperone-based therapeutic approaches. Neurochem Res. 34: 755–763

Darnell JC 2014. Ribosome rescue and neurodegeneration. Science 345: 378-379  

Escande C et al 2013 Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism. Diabetes 62:1084-93

Farzaei MH et al 2013 Parsley: a review of ethnopharmacology, phytochemistry and biological activities. J Tradit Chin Med. 33:815-26

Hahm J et al 2019. Diet restriction‐induced healthy aging is mediated through the immune signaling component ZIP‐2 in Caenorhabditis elegans. Intl Fed Assoc Anatomists. 19th Congress. https://doi.org/10.1111/acel.12982

Johnson S, Imai S 2018. NAD + biosynthesis, aging, and disease. F1000Res 7: 132. PMID: 29744033

Kikis EA, Gidalevitz T, Morimoto RI 2010. Protein homeostasis in models of agingand age-related conformational disease.  Adv Exp Med Biol  694: 138–159. PMCID: PMC3402352 NIHMSID: NIHMS311662 PMID: 20886762

King, G, Beins, M, Larkin, J, Summers, B, and Ordman AB 1994. Rate of Excretion of Vitamin C inHuman Urine. AGE 17:87-92 

Maresz K 2015. Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integr Med (Encinitas) 14(1): 34–39. PMCID: PMC4566462 PMID: 26770129

NIH. Accessed 2019. Causes of Alzheimer’s disease: What Happens to the Brain in Alzheimer’s Disease? https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease

SENS Research Foundation 2019. The Root Causes of Aging. 

https://www.fightaging.org/archives/2019/06/exosomes-in-harmful-senescent-cell-signaling/

Tanaka K 2009. The proteasome: Overview of structure and functions. Proc Jpn Acad Ser B Phys Biol Sci 85: 12–36. doi: 10.2183/pjab.85.12 PMCID: PMC3524306 PMID: 19145068

Wang P, Heber D, Henning SM 2012. Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells. Nutr Cancer 64:580-7. doi: 10.1080/01635581.2012.

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