Amino Acids and Nucleos . . . The One, Two Punch?

DRAFT PAGE – MORE EXCITING INFO COMING SOON!

TERMINOLOGY

ESSENTIAL NUTRIENT: An “Essential Nutrient” is one required through dietary intake in order for the body to function properly. Essential Nutrients must be consumed frequently and in adequate quantities for the body to function. Essential nutrients include: water, fat (fatty acids), protein (amino acids), vitamins and minerals.

“Essential Amino Acids” (EAA) and “Essential Fatty Acids” (EFA) are subsets to Essential Nutrients that the body has no way to synthesis (can’t create them from other nutrients). We will discuss these more in-depth later.

IMPORTANT NOTE REGARDING LOW CARBOHYDRATE DIETS and FATTY ACID METABOLISM DISORDERS: There has been a shift in the research that questions carbohydrates as an essential nutrient. However, it is impractical to completely eliminate carbohydrates from the diet. In fact, inclusion of low carbohydrate, fiber-rich foods can play a role in providing important vitamins and minerals. Although the benefits of a low carbohydrate, high healthy-fat diet continue to mount, there are always caveats that require consideration. Certain disorders, including some liver and gall bladder issues, defects of Gluconeogenesis or one of several Fatty Acid Metabolism disorders, could make fat consumption detrimental and require frequent small meals containing dietary carbohydrates as the main source of glucose to drive metabolic processes.

HOW IMPORTANT IS NUTRITION?

In my quest to find ways to heal my Mitochondria, I ran across cellular biology research that was occurring right in my own hometown. At the University of South Alabama, researchers discovered that Mitochondrial DNA had a repair sequence (like a repair program). This was an amazing discovery based on diligent observation. Studying Mitochondria over the long-term, they realized that damaged DNA was self-correcting, though it was an extremely slow process, which is why no one had caught it before.

Scouring their website failed to reveal any contact information for these researchers, but I did find an article announcing their brand new facility. I did what any desperate, bullheaded patient would have done. I drove the campus until I found their new facility and started wondering the halls seeking one of these researchers. After watching me shuffling up and down the halls, out of breath and hunched over my rollator, a nice young man showed me to the Department Head’s door. I paused nervously. Finding an expert so close to me was so exciting that I got in my car and drove there not even knowing what I was going to say. I took a deep breath and knocked. “Come in.” After confirming he was one of the contributors to the study, I froze for a moment before blurting out, “Can I take you to lunch and pick your brain about Mitochondria?” (After all, it was lunchtime.) Puzzled, he asked if I were a student. I said, “No,” looking down at my rollator, “I’m a Mitochondrial patient.” Graciously, he responded, “You don’t have to take me to lunch. Just sit down. What do you want to know?”

For the next two hours, I listened to an excited researcher describe the latest research in Mitochondria. He explained how the processes of aging and disease were greatly influenced by what was termed, “Mitochondrial DNA Repair Rate”; the speed and effectiveness of Mitochondria to deal with deletions and other damage that effect Mitochondrial DNA and impact overall Mito function. I couldn’t help getting hopeful as he spoke about their current project aimed at increasing DNA Repair Rate in cardiac tissue following a heart attack. I guess he could see that hope in my face. He paused his discussion to caution me, “What we are working on won’t improve your particular condition.” And if that wasn’t bad enough news he continued, “And I wouldn’t expect a cure for your form of Mitochondrial damage in your lifetime….” It was harsh to hear. There simply were not enough people with my condition to garner the attention or funding of the pharmaceutical industry. Then he confirmed to me what most people already speculate. “We uncover information that prompts us to take different paths in our research. However, we are prevented from pursuing those paths unless we can convince a pharmaceutical company to fund it. It’s the cold, hard truth; but somebody has to pay the bills and the bills are expensive.” Also not a surprise, he confirmed that drug companies were not in the business of finding cures; but to identify conditions effecting large numbers of people and develop a pill those people will have to take for the rest of their lives.

He hadn’t told me anything I didn’t already believe to be true. But I have to admit, his words came with full force and effect, him being someone so intricately tied to the business. I remember sitting there like the life had been sucked out of me. I don’t know what I expected to get out of this meeting, but I imagined it a much happier occasion. Whether it was sympathy or straight up pity, he spoke up again while reaching for a post-it note. “Look, I’m going to write something down and I want you to go look it up. Several universities are performing clinical trials with it right now. It isn’t a cure, but I think it will help.”

Jotted down on the post-it was “Nicotinamide Riboside.” They were using a synthesized form of B3 to improve Mitochondrial function and stimulate mtDNA Repair. I was absolutely shocked that some the best research on improving Mitochondrial function focused on a readily available nutrient! Over the years, more Mitochondrial clinical trials were being reported. But as with Columbia, they each were utilizing different components or analogues of other nutrients and nutrient compounds. EVERY SINGLE ONE OF THEM!

Dichloroacetate: An analogue of Pyruvate (which comes from glucose from splitting sugars or from fatty acid oxidation).

Arginine: An Essential Amino Acid.

CoQ10: Both the natural form of the antioxidant CoQ10 (Ubiquinone and Ubiquinol) and Idebenon (a CoQ10 derivative).

RTA-408 (Omaveloxolone): A synthetic Oleanane Triterpenoid. Oleanane is a natural Triterpene found in certain flowering plants.

EPI-743: Based on Vitamin E sourced from sesame seeds and sesame seed oil.

Creatine: A tripeptide produced from the Amino Acids Arginine, Glycine and Methionine.

Creatine, CoQ10 and Lipoic Acid: Creatine (Tripeptide), CoQ10 (Antioxidant), Lipoic Acid (Antioxidant).

Then came MTP-131, better known as Bendavia, Elamipretide, or Ocuvia and formerly referenced as SS-31. A friend contacted me to let me know she was entering the clinical trial. I had barely heard of this “drug” before; but seeing that every other “drug” that had been tested turned out to be nutrient-based, I decided to do a little digging. I eventually found a medical journal article that disclosed the chemical name and structure. (H-d-Arg-Dmt-Lys-Phe-NH 2 , Dmt = 2′,6′-dimethyl-Tyr).

Breaking down the formula, this is what is revealed:

There are two main parts to this drug. FIRST is a group of Amino Acids (D-Arginine, Dimethyl-Tyrosine, Lysine, Phenylalanine). This grouping of amino acids have a high affinity to be “readily taken up by a variety of cell types without the need for specific transporters or receptors,” and also has “highly selective mitochondrial targeting.” “Unlike lipophilic cations such as MitoQ, the uptake [of the family of compounds referred to as Szeto–Schiller (SS) peptides] does not rely on mitochondrial potential (in other words, does not rely on gradient effect) and it does not cause mitochondrial depolarization.” (See Serendipity and the Discovery of Novel Compounds That Restore Mitochondrial Plasticity, 2014.)

This grouping of Amino Acids also provides capacity to carry other nitrogen and hydrogen molecules (the H and the NH2 in the formula represent the additional bonding). And since the compound targets Mitochondria and readily passes barrier membranes, it delivers these high energy electrons directly to the Mitochondrial Matrix for use in the Electron Transport Chain (ETC), the most effective method of generating ATP-energy.

SECOND, the NH2 in the formula is also associated with Cytosine, one of four nucleobases: Adenine and Guanine are double-ringed purines and Cytosine/Uracil and Thymine are Pyrimidines. Just to get a glimpse at how important nucleobases are, consider that Adenine, in conjunction with D-ribose, creates Adenosine… otherwise known as the “A” in Adenosine Triphosphate or ATP. Cytosine is equally as important to ATP production. Not only does Cytosine provide additional Nitrogen and Hydrogen into the ETC, it goes on to be converted into Cytidine Triphosphate (CTP), thus able to donate phosphates to the creation of ATP.

MTP-131 studies are showing great promise in improving ATP production. The intravenous form was boasted for improving ATP production in as little as two hours post IV administration. But for study participants, the results could wear off in a matter of hours following treatment. Knowing the nutrient-based chemical structure of MTP-131, it wasn’t a big leap to speculate that the benefits were so brief and temporary because the body had completely utilized the nutrients that had been provided.

The question became, if these substances are readily available in whole food sources, could a diet rich in these foods help the body improve functioning like MTP-131 was being studied for? IV delivery could potentially aid in delivery of these substances, thus likely better overall results. But since oral and topical delivery of MTP-131 is now being studied, my curiosity was definitely heightened over whether dietary intake could stimulate similar improvements.

“These amino acid–based compounds have surprisingly remarkable drug-like properties, making us question many of the old dogmas about drug design in the pharmaceutical industry.” (See Serendipity and the Discovery of Novel Compounds That Restore Mitochondrial Plasticity, 2014.)

AMINO ACIDS: WHAT YOU SHOULD KNOW

Up to 20% of the human body is protein. Amino Acids make up those proteins. When we think of protein, we often think of muscle. This is not the whole picture because Amino Acids are found in every microscopic corner of our existence. There are 270+ Amino Acids. Humans depend on 20 Amino Acids designated as “proteinogen” (able to build protein components). The importance of these Amino Acids should not be ignored. Through Protein Biosynthesis, the body uses these 20 Amino Acids and transforms them into literally hundreds of biological protein structures that perform functions all over the body. These structures influence our metabolic processes (Mitochondria) and play important roles in detoxification and waste removal, gland and organ function, hormone function, and are intricately tied to healing / regeneration in every tissue and structure of the body (including Mitochondrial DNA repair). Additionally, Amino Acids are also the catalyst for countless other chemical reactions that occur in the body. This is why I stress the importance of NOT focusing on one or just a few Amino Acids, but rather using multiple food sources with a wide variety of all relevant Amino Acids.

Of the Proteinogen Amino Acids, there are three groups: Essential, Conditionally Essential, and Non-Essential. But as I am finding in several realms, don’t get too hung up in the descriptive words or it will lead you astray. All 20 Amino Acids are essential to optimal health. These terms only refer to how they are obtained by the body. But as you will see, even those that can be synthesized internally require the precursors that are often other Amino Acids or other nutrients.

NOTE: The body cannot store amino acids. Therefore, consumption of a full complement of Amino Acids should be done throughout the day, every day.

ESSENTIAL AMINO ACIDS:

The body CANNOT synthesize (create) these Amino Acids. They must be acquired from protein sources that contain these individual nutrients. There are 10 Essential Amino Acids:

Arginine

Histidine

Isoleucine

Leucine

Lysine

Methionine

Phenylalanine

Threonine

Tryptophan

Valine

CONDITIONALLY ESSENTIAL:

Certain conditions can make a Conditional Amino Acid become an Essential Amino Acid. There are 6 Conditional Essential Amino Acids:

Arginine: Essential for pre-term infants or other conditions interfering with synthesis of Arginine.
Also essential for people experiencing severe catabolic distress.

Cysteine: Considered an Essential Amino for infants, elderly, those with certain metabolic disorders or certain malabsorption syndromes. Produced from Methionine; thus, a Methionine deficiency will cause a Cysteine deficiency.

Glycine: Produced from Serine (and also requires Pyridoxal 5′-Phosphate [active form of B6] and a Methyl- based Folate). Deficiencies in any of these can cause a deficiency of Glycine. Additionally, there is some evidence that metabolic biosynthesis is not sufficient to properly support collagen synthesis; this would indicate Glycine is closer to being an Essential Amino Acid.

Glutamine: Excessive stress can increase Glutamine demand past synthesis capabilities, requiring increased dietary intake of Glutamine.

Proline: Produced from Glutamic Acid; thus, a Glutamic Acid deficiency will cause a Poline deficiency.

Tyrosine: Produced from Phenylalanine; thus, a Phenylalanine deficiency will cause a Tyrosine deficiency. It is also highly water soluble; therefore, it can be flushed quickly from the body requiring higher consumption.

NON-ESSENTIAL:

The body can produce these Amino Acids, given the right precursors. There are 5 Non-Essential Amino Acids:

Alanine: Can be manufactured from Pyruvate and Branched Chain Amino Acids (Valine, Leucine, and Isoleucine)

Asparagine: Synthesized by transferring the amino group from Glutamate to Oxaloacetate, creating α-Ketoglutarate and Aspartate. Also synthesized from Aspartate, Glutamine, and ATP by the enzyme Asparagine Synthetase; producing Asparagine, AMP, Glutamate, and Pyrophosphate.

Aspartic Acid: Synthesized by transferring the amine group from Alanine or Glutamine. Also created as a byproduct of the Urea Cycle.

Glutamic Acid: Glutamic Acid can be synthesized by at least seven (7) different reactionary biological processes.

Serine: Synthesized from Glycine and Threonine.

EXCELLENT SOURCES OF AMINO ACIDS:

EGGS! Anyone who knows me knows how much I advocate for eating eggs… and lots of them. In regards to total nutrient value, eggs top out on the super food list and crops up in more research than you can shake a stick.
Note:  Eggs do not cause high cholesterol. Diets high in carbohydrate intake cause the liver to produce high levels of a different form of cholesterol than the cholesterol we consume from food. I eat no less than 2 eggs a day, usually 3 to 6 on average. The doctors keep telling me it is going to give me high cholesterol and high blood pressure; however, I’ve been doing this all my life, and especially since 2012 and both my blood pressure and cholesterol level is remarkable. (Also, eggs contain nucleo-bases that can bind with Ribose to create Nucleosides. We will talk about this below.)

MEAT: red meat being the highest (red meat is also the highest in naturally occurring Carnitine and the best absorbed form of Carnitine [80% absorption verses 14-18% from supplements!])

Chicken and Turkey

Salmon (cold-water, wild Alaskan is the best, and also contains the full range of Omegas in the proper ratios that can help reduce inflammation rather than cause it)

LENTILS: lentils and blackeyed peas contain a lot of amino acids (and are one of the best non-organ-meat sources of Nucleotides.) HOWEVER, you need to consume Methionine with them in order to utilize the aminos. In fact, this is true with most amino acids… they need the amino Methionine in order to be used properly. Yet another reason one should not focus on only a few amino acids but rather a full complex of aminos.

COOKING AND ITS IMPACT ON AMINO ACID CONTENT:

There is little evidence that cooking food to temperatures up to 212 degrees F (100 degrees C) are destructive to Amino Acids. Temperatures above 212 degrees F and extended cooking times can impact nutrient content.

Check out my recipes for Whey Protein Shakes and Homemade Aloe Water:

CLICK HERE FOR HEATHER’S WHEY PROTEIN SHAKE RECIPE

CLICK HERE FOR HEATHER’S HOMEMADE ALOE WATER RECIPE

 

NUCLEOBASES / NUCLEOSIDES / NUCLEOTIDES (NUCLEOs): WHAT YOU SHOULD KNOW

Nucleos have been utilized successfully by farmers and in veterinarian medicine for decades. Nucleos were identified as a vital component in breast milk, with particularly high levels in human breast milk. Eventually, in the 1960s, Nucleos were determined to be at least semi-essential nutrients that were necessary components that needed to be added to baby formula to avoid conditions such as failure to thrive, neurological disorders, GI disorders, and poor immunity.

Nucleotides have become a huge focus of research. I will let the research speak for itself:

Nucleotide Supplementation for Infants

(1998) The role of dietary nucleotides in neonatal and infant nutrition.

(1999) Dietary Nucleotide Supplementation Raises Erythrocyte 2,3-Diphosphoglycerate Concentration in Neonatal Rats.

(2002) Scientific rationale and benefits of nucleotide supplementation of infant formula.

(2007) Immune response to nucleotide-supplemented infant formulae: systematic review and meta-analysis.

Research on Nucleo- effects on Various Aspects of Health

(1994) The role of nucleotides in adult nutrition.

(1994) Dietary nucleotides: cellular immune, intestinal and hepatic system effects.

(2006) The effects of a nucleotide supplement on salivary IgA and cortisol after moderate endurance exercise.

(2007) The effects of a nucleotide supplement on the immune and metabolic response to short term, high intensity exercise performance in trained male subjects.

(2012) The role of nucleotides in the immune and gastrointestinal systems: potential clinical applications.

(2012) Sublingual nucleotides and immune response to exercise.

(2013) Dietary nucleotide improves markers of immune response to strenuous exercise under a cold environment.

(2013) Sublingual Nucleotides Prolong Run Time to Exhaustion in Young Physically Active Men.

(2015) Performance-enhancing effects of dietary nucleotides: do mitochondria play a role?

(2017) Nucleotide pools dictate the identity and frequency of ribonucleotide incorporation in mitochondrial DNA.

Whole Food Options for Nucleos

Researching whole food options for Cytosine was proving more difficult, and a lot less appealing. Foods richest in Cytosine are those foods rich in Nucleobases (DNA and RNA) like organ meat; heart, liver, kidney, brain…. Now if you enjoy organ meat, by all means, enjoy your organ meat. For me, the thought was a little “hard to swallow.” But one day while consuming my daily dose of fresh yard eggs I had an epiphany, “Why on earth was I NOT coming up with eggs as a source for Nucleos? Eggs (whether from chickens, fish, etc.) are the epitome of being a vessel for delivery of DNA and RNA… which are made up of those four nucleobases Adenine, Guanine, CYTOSINE / Uracil and Thymine. Other sources of Nucleos include lentils (pulse), blackeyed peas, and split peas. Also, ginger (which I already use daily in an extract liquid form) and RAW (local, unpasteurized) honey. Although quantities aren’t as significant, fresh fruits and vegetables also contain some amounts of Nucleos including: apples, oranges, bananas, strawberries, tomatoes, green leafy vegetables and seeds. Maybe an apple a day really can help keep the doctor away. 😉 Though whole grains can also provide Nucleos, this source should be used sparingly if you have determined you have issues with gluten, or feel better on a low- or no gluten diet.

Supplementing Necleos

Adenine, Guanine, Cytosine / Uracil and Thymine each can combine to form other extremely important compounds that help run the great many processes that give us live and support our health. These Nucleobases help form DNA and RNA, play an important role in immune capabilities, and contribute significantly as a vital precursor to ATP production in a multitude of ways. Nucleobases join with D-Ribose (a 5-carbon sugar) to form Nucleosides. When these Nucleosides join with one or more phosphate groups they become Nucleotides. (In the case of the Nucleobase Adenine, in combination with D-Ribose it forms the Nucleoside version called Adenosine, which is the “A” in FAD/FADH2 and NADH, NAD+. When the Nucleoside Adenosine combines with the phosphate group it becomes ATP/ADP/AMP.)

Nucleos cannot be isolated from their whole food source without rendering them useless. However, Nucleos can come in a supplement utilizing the whole food. The Nucleo Immune contains all the major Nucleotides sourced from Brewer’s Yeast. There are other options coming on the market. A good rule of thumb when comparing Nucleo supplements is whether or not they bother to tell you on the label where their Nucleos are being sourced from. If they don’t disclose the source, don’t waste your money.

⬅️ Diet and Nutrition

⬅️ Supplementation

⬅️ Hydration

Amino Acids and Nucleo Intake