“Krebs Cycle intermediates reflect how efficiently your cells convert food into energy via the mitochondria.”

 

For more details on the Krebs Cycle, you can read more about it as part of the MTHFR series, click here.

In an Organic Acid Test (OAT), the Krebs Cycle Intermediates (also called the Citric Acid Cycle or TCA Cycle) assess the efficiency of your body’s cellular energy production system—specifically, how well your mitochondria are converting carbohydrates, fats, and proteins into ATP (energy).

🔬 Key Metabolites Measured Under Krebs Cycle Intermediates:

1. Citric Acid (Citrate)

   • First step in the cycle (formed from acetyl-CoA + oxaloacetate)

   • High = possible mitochondrial overload or blocked downstream steps

   • Low = poor carbohydrate or fat intake, B-vitamin deficiency

2. Cis-Aconitic Acid (Aconitate)

   • Formed from citrate by aconitase (iron-dependent)

   • Sensitive to oxidative stress and iron deficiency

3. Isocitric Acid (Isocitrate)

   • Isomer of citrate; used to produce α-ketoglutarate

   • High = block in the downstream enzyme, low NAD+

4. α-Ketoglutaric Acid (Alpha-Ketoglutarate)

   • Central molecule in energy metabolism and amino acid processing

   • Elevated in B-vitamin (especially B1, B3) or magnesium deficiency, or gut dysbiosis

5. Succinic Acid (Succinate)

   • Converted to fumarate via succinate dehydrogenase (complex II of the electron transport chain)

   • High = B2 (riboflavin) or CoQ10 deficiency, mitochondrial stress

6. Fumaric Acid (Fumarate)

   • Part of the energy conversion cycle

   • High = possible downstream enzyme block or oxidative stress

7. Malic Acid (Malate)

   • Recycles to oxaloacetate, continuing the cycle

   • High = impaired conversion due to low NAD+, magnesium, or mitochondrial strain

🧬 Clinical Significance:

• Disruptions in this section suggest:

  • Mitochondrial dysfunction

  • B-vitamin deficiencies (especially B1, B2, B3, B5)

  • Magnesium deficiency

  • Toxin overload or oxidative stress

  • Impaired energy production (ATP synthesis)

Dr Lindenberg comment: Low levels of Krebs Cycle Metabolites

Succinic acid                                               10.09 (result)  L / 16 – 156 (range)

A low succinic acid level typically means that there’s reduced activity or throughput in the Krebs (TCA) Cycle, particularly at the step where alpha-ketoglutarate is converted into succinate, and onward to fumarate.

🔍 What Succinic Acid Represents:

• Succinic acid (succinate) is a key intermediate in the Krebs Cycle, involved in mitochondrial ATP production.

• It is also involved in complex II of the electron transport chain, linking energy production with antioxidant regulation (via FADH₂ and CoQ10).

🔽 Possible Reasons for Low Succinic Acid:

✅ 1. Low Mitochondrial Activity / Low Energy Demand

• Seen in:

  • Sedentary lifestyle

  • Low metabolic rate (e.g., hypothyroidism)

  • Low calorie or carb intake

  • Chronic fatigue

✅ 2. B-Vitamin Deficiency

• Especially Riboflavin (B2) – essential for succinate dehydrogenase

• Also possibly B1, B3, and B5, which support other Krebs cycle enzymes

✅ 3. Low Substrate Availability

• Not enough acetyl-CoA, often due to:

  • Poor glucose or fat breakdown

  • Protein deficiency (amino acids needed for TCA cycle entry)

  • Fasting or restrictive diets

✅ 4. Magnesium or CoQ10 Deficiency

• Both are essential cofactors in the Krebs cycle and oxidative phosphorylation

✅ 5. Efficient Krebs Cycle Flow

• In rare cases, a low level may simply reflect efficient use and minimal excess of succinate, particularly when all other cycle intermediates are also low and the person is healthy.

⚠️ Context Is Key:

Low succinic acid is best interpreted in combination with:

• Other Krebs cycle intermediates (e.g., citrate, alpha-ketoglutarate, fumarate)

• Energy-related markers (e.g., lactate, pyruvate, ketones)

• Nutrient markers (e.g., B-vitamins, carnitine-related markers)

Foods that contain Succinic acid include broccoli, rhubarb, sugar beets, fresh meat extracts, various kinds of cheese, and sauerkraut.  

 

2-Ketoglutaric acids/ 2-Oxoglutaric acid             1.72 (result)  L / 36 – 103 (range)

A low 2-Ketoglutaric acid (also known as α-Ketoglutaric acid or 2-Oxoglutaric acid) suggests reduced activity or input in the Krebs cycle and can point to several possible physiological or nutritional issues.

🔬 What is 2-Ketoglutaric Acid?

• A central intermediate in the Krebs (TCA) Cycle, formed from isocitrate and converted into succinyl-CoA.

• It plays a critical role in:

  • Energy production (ATP)

  • Amino acid metabolism (especially glutamate ↔ alpha-ketoglutarate)

  • Nitrogen balance and detoxification (via the urea cycle)

  • Neurotransmitter balance (glutamate/GABA cycling)

🔽 What Low 2-Ketoglutaric Acid May Indicate:

✅ 1. Low Krebs Cycle Activity

• May result from:

  • Low mitochondrial function (fatigue, chronic stress, illness)

  • Reduced fuel availability (low carb, protein, or fat intake)

  • Thyroid or adrenal insufficiency (low metabolic demand)

  • Ageing or sedentarism (reduced energy turnover)

✅ 2. Low Glutamate or Amino Acid Input

• Alpha-ketoglutarate is also produced from glutamate deamination

• Low levels can reflect:

  • Low protein intake

  • Poor digestion/absorption of amino acids

  • Impaired transamination reactions (B6-dependent)

✅ 3. B-Vitamin Deficiency

• Especially:

  • Vitamin B1 (thiamine)

  • Vitamin B3 (niacin/NAD)

  • Vitamin B5 (pantothenic acid)

These are needed for the proper function of the enzymes in this part of the TCA cycle.

✅ 4. Magnesium or Manganese Deficiency

• These are cofactors for enzymes involved in the TCA cycle.

✅ 5. Efficient Utilization

• In some cases, low levels may simply reflect efficient conversion/use of alpha-ketoglutarate with no excess excretion.

• This is more likely if the person is otherwise healthy, and other energy markers are normal.

 

Citric Acid                                                           31.44 (result)   / < 656

A low citric acid (also called citrate) typically indicates reduced entry of acetyl-CoA into the Krebs (TCA) cycle, and therefore reduced mitochondrial energy production.

🔬 What is Citric Acid?

• The first molecule formed in the Krebs cycle when acetyl-CoA (from carbohydrates, fats, or proteins) combines with oxaloacetate.

• Its levels reflect how well your body is generating energy from food.

🔽 What Low Citric Acid May Indicate:

✅ 1. Low Substrate Availability

• Not enough acetyl-CoA entering the Krebs cycle due to:

  • Low calorie or carb intake

  • Poor fat metabolism

  • Low protein intake

  • Fasting or restrictive diets

✅ 2. Mitochondrial Dysfunction

• Mitochondria are struggling to process fuel efficiently.

• Common in:

  • Chronic fatigue

  • Neurodegenerative diseases

  • Oxidative stress

✅ 3. B-Vitamin Deficiency

• Especially:

  • B1 (thiamine) – needed to form acetyl-CoA

  • B3 (niacin) – for NAD⁺, a key cofactor

  • B5 (pantothenic acid) – precursor to CoA

✅ 4. Magnesium Deficiency

• Required for citrate synthase, the enzyme that forms citrate from acetyl-CoA and oxaloacetate.

✅ 5. Low Metabolic Demand

• Low thyroid function, chronic stress, or sedentarism may decrease the need for ATP production and reduce citrate levels.

✅ 6. Efficient Utilisation (less likely)

• In rare cases, low citrate may mean the cycle is running efficiently and not producing excess to be excreted.

Interestingly, Malic acid contributes to the “sour” taste in fruits and vegetables, such as apples, grapes, and rhubarb.

Elevations in Krebs Cycle metabolites are commonly due to environmental toxins such as heavy metals or mould, yeast/fungal or bacterial overgrowth, high oxalate levels, or high oxidative stress. A less common indication of high levels would be a genetic issue.

 

PLEASE NOTE: ANY VIEWS REGARDING THE RESULTS ARE MY UNDERSTANDING AND DO NOT SERVE AS PROFESSIONAL ADVICE. THE TREATMENT RECOMMENDATION IS STRICTLY RELATING TO ALEX’S RESULTS AND IS NOT MEANT FOR SELF-TREATMENT. ALWAYS SPEAK TO YOUR HEALTHCARE PROVIDER BEFORE STARTING ANY TREATMENTS.