KREBS CYCLE INTERMEDIARIES-OXYGEN AND VINEGAR FATIGUE TEST

June 30th, 2017 - Brian Maguire

A fairly large percentage of the diets and lifestyles in industrialized nations, like the US in particular, tend to be acidogenic.

This means a typical diet is high in acid forming animal protein, refined grains, sugar, and iodized table salt, low in alkaline forming fruits and vegetables, and lifestyles high in multitasking stress. These habits lead to latent or low-grade chronic metabolic acidosis, and the overproduction of lactic acid at the cellular level!

As discussed in previous sections, these are some of the major causes and results of Krebs cycle malfunction as oxygen levels diminish and cellular consumption of nutrients and excretion of waste is jeopardized. The electron transport chain (part of the Krebs or citric acid cycle) is inhibited and cannot be completed in a low oxygen environment , initiating oxidative stress, and increasing free radical production. As a result, mitochondrial cellular energy is further diminished leading to increased intra-cellular oxidative stress. This ADVANCES the aging process, introduces a host of illnesses, and makes it much harder to restore homeostatic balance.

So how does diet come into play? In a nut shell, the food that you eat contains stronger acids or weaker acids. Stronger acids are typically found in high protein foods like meats, eggs, commercial dairy and grains, and damaged processed food products. These are high in protein and acid minerals and oxidize into sulfuric, phosphoric, and uric acids, which are highly net-acid producing.

On the contrary, most fruits and vegetables are net alkaline forming foods as they are low in protein and high in alkaline minerals calcium, magnesium, organic sodium, and potassium. However, not all of them are alkaline forming due to their alkaline mineral content alone. Many fruits and vegetables, some more than others, contain certain weak or organic acids like citric, malic, fumaric, succinic, acetic, and more. This may sound somewhat paradoxical, but it’s also the weak acids in these foods that commence an alkaline response as well.

Citrate is an alkaline forming derivative of citric acid and is an intermediary in the central metabolic pathway. Citrate is part of a sequence of compounds involving the oxidation of acetate (derivative of acetic acid) from macronutrients (carbs, fats, proteins) that you consume on a daily basis provoking a chain of chemical reactions to produce energy via the Krebs Cycle.

With that being said, the citric acid cycle does not require citric acid from fruits and vegetables to function per say. However, being that citrate is an intermediary in the Krebs cycle, if you consume foods, or take certain supplements that contain citric acid or citrates, it can work wonders to augment the functioning and efficiency of this aerobic energy producing Cycle! Citric acid is found in larger quantities in lemons, limes, oranges, and grapefruits, pineapples, tomatoes, and onions, with lemons and limes being the most alkaline forming.

The same goes for malic acid found in certain fruits and vegetables and naturally formed in your body’s cells in the form of malate. Apples are high in malic acid and form another Krebs Cycle intermediary called malate. Besides in apples, malates are also formed in higher amounts in apple cider vinegar, which also contains acetic acid, another player in the Krebs cycle, making it a very powerful anti-inflammatory alkalizer. Cider vinegar with its malates and acetates is touted as a miraculous remedy for painful gout and other forms of arthritis, as it neutralizes uric and other acids that collect in the joints and extremities.

These acetates, malates, and citrates are paired up with alkaline minerals like sodium, potassium, magnesium, and calcium, formed in our foods and through dissociation upon digestion of foods that contain citric acid, acetic acid, or malic acid, and act as Citric Acid Cycle intermediary helpers.

When weak acids like in apple cider vinegar or citric acid in lemons partially dissociate they become ready to act as a base or alkali as only some of its protons are lost and is therefore ready to accept protons (H+) or acids, and that cycle continues producing alkaline by-products. These weak acids have the propensity to NEUTRALIZE the H+(acid) that increases from ingesting too many stronger acid producing substances!

Conversely, strong acid by-products from meats like sulfuric acid largely dissociate giving up their protons (H+), releasing acid into the body’s fluids lowering pH levels. So, besides the digestive fire in the stomach that requires strong Hydrochloric acid to digest your food, you can say strong acids are weak in excess, and weak acids are strong for the body.

The Krebs cycle intermediates proves to directly impact acid/alkaline balance! Citric acid like in lemons and malic acid and acetic acid found in cider vinegar induce acetate, citrate, and malate intermediates that feed the Krebs cycle generating the alkaline end product sodium bicarbonate which raises urine pH. With all the wonderful health promoting benefits of these weak acids if behooves the majority of us to consume them on a regular basis!

Here is the raw science behind citrate as an intermediate in the Krebs cycle! When oxygen is present, the pyruvate dehydrogenase complex forms acetyl-CoA, from pyruvate and five co-factors (thiamine pyrophosphate, lipoamide, FAD, NAD+, and CoA), citrate synthase catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate then continues in the TCA cycle via aconitase, at some point regenerating oxaloacetate, which can combine with another molecule of acetyl CoA and continue cycling. 

Magnesium, which is responsible for over 300 biochemical reactions in the body, is also a MAJOR player in the production of ATP cellular energy production. Magnesium is required to assist in half of the 23 or so ATP energy producing phases of Glycolysis, the Krebs, and Electron Transport Chain. Most people are deficient in this critical mineral that supports cellular energy which supports disease prevention and longevity.

Studies show when you consume foods or supplements that are high in these Krebs Cycle intermediates like malates, and citrates, along with sufficient supporting minerals like magnesium and potassium, it can have a profound effect on acid/alkaline balance and overall health status. Citrates, malates, and succinates have also been found to have a strong affinity for calcium, PREVENTING and DISSOLVING stones and other highly damaging calcifications in the joints and soft tissues, as well as life threatening calcifications in the arteries. In addition, their ability to counteract acid waste buildup helps to prevent bone loss and the resultant calcium deposits.

Researchers and authors Caudarella R1, Vescini F., who published Urinary citrate and renal stone disease: the preventive role of alkali citrate treatment (Pub Med 2009), are convinced on the alkalizing power of Citrate. Their data shows; “Citrate is a weak acid that is synthesized inside Krebs’ cycle. It can also enter the body through dietary intake. The protective role of citrate is linked to several mechanisms; in fact citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. Furthermore, citrate increases the activity of some macro-molecules in the urine (e.g. Tamm-Horsfall protein) that inhibit calcium oxalate aggregation.

The therapy with potassium citrate, or magnesium potassium citrate, is commonly prescribed in clinical practice in order to increase urinary citrate and to reduce stone formation rates. Our data, as well as those of the literature, confirm that alkali citrate induces both an increase of protective urinary analytes (e.g. citrate, potassium and pH) and a decrease of calcium oxalate supersaturation.

Moreover, alkali treatment reduces the rate of stone recurrence and increases the clearance rates and dissolution of stone fragments. Last but not the least, an increasing number of papers pointed out the protective role of alkali citrate in preserving bone mass in stone former’s as well as in healthy subjects with bone loss.”

According to Fredric Coe, MD, Professor of Medicine; Medical Director, Kidney Stone Prevention Program; Director, Clinical Research Training Program at The University of Chicago Medicine, “Those unfamiliar with the matter may not realize that the diet we eat in the US and most of the other first world countries imposes an acid load that must be excreted daily in the urine. So the urine citrate excretion we find in our clinics and in experiments on ‘normal’ diets are those consistent with an acid load. When we give potassium citrate or other alkali we often do little more than neutralize this acid load, yet urine citrate usually rises.” When we give potassium citrate or any other alkali in doses of 40 to 60 mmol/day or (1.5-2.5 grams), we neutralize a large fraction of diet acid. This is best considered not so much as an ‘alkali load’ as it is the removal of that acid load to which we have long been adapted.”  

Adding to the words of acid/base expert Fredric Coe, so called ‘normal’ Western Diets are highly acid forming and initiate an incredible burden on the body, especially invaluable organs like the kidneys. If you are to have any chance of preserving your health and avoiding the onset of disease, establishing a more alkaline forming diet and lifestyle is primordial for most.

NOTE: potassium citrate was used in a clinical setting and should not be taken in high doses unless under doctor supervision. Large doses of supplemental potassium can throw off electrolyte balance and lead to an irregular heartbeat. Being that most people are deficient in magnesium, magnesium citrate would be a better option. Primarily, opt for increasing consumption of whole foods like potassium rich fruits and vegetables to optimize pH.

Succinate is a citric acid cycle intermediate like citrate, but its uptake by the citrate transporter is not affected as much by the acidity or alkalinity of the medium (pH). Citrate uptake, however, is powerfully affected which shows a comparison of the two intermediaries in this study. 

Malic acid has been shown to SIGNIFICANTLY improve muscle performance! It reduces muscle fatigue after exercise by reversing lactic acid buildup, and increases energy levels and overall mental clarity as tissues are oxygenated. So, whether you are experiencing fatigue, brain fog, joint or muscle pain, digestive issues, or suffering from the debilitating effects of fibromyalgia or Chronic Fatigue Syndrome, malic acid can be highly beneficial.

Researchers and scientists working at the Department of Medicine, University of Texas Health Science Center in the US performed a six-month study. They gave 1,200 mg of malic acid plus 300 mg of magnesium a day to 24 fibromyalgia sufferers and evaluated the effect it had on them. Half of the patients were given the malic acid treatment, while the rest received a placebo.

The scientists concluded that all the patients treated with malic acid and magnesium experienced significant improvements, including less pain, reduced muscle stiffness, increased mental clarity, and overall happiness.

Dr. Russell, who led the team of scientists, stated “The data suggest that malic acid and magnesium are safe and may be beneficial in the treatment of patients with fibromyalgia. Future studies should use malic acid at this dose and continue the therapy for at least two months”

VINEGAR TEST– Consuming 1-2 tbs of apple cider vinegar (ACV) in 8 oz of water begins to eliminate fatigue in less than two hours.

You can prove this by examining your urine a few hours after you take the vinegar. You will notice it to be clearer.  In addition take a pH strip or litmus paper and test the urine pH.  Before you take vinegar and two hours after you take vinegar. The test strip will read more alkaline two hours after you take the vinegar as fatigue promoting excess acidity diminishes.

Some of us, most often temporarily, may be metabolically handicapped so to speak, so weak acids may be an issue and need to be buffered until the imbalance is corrected.

**For those who have trouble metabolizing weak acids refer to issues metabolizing fruit and weak acid