Vitamin B1 (Thiamine) and B2 (Riboflavin): Energy Production and Mitochondrial Health in Older Adults

Thiamine (vitamin B1) and riboflavin (vitamin B2) are water‑soluble micronutrients that sit at the core of cellular energy metabolism. In older adults, where mitochondrial efficiency naturally declines, adequate supplies of these two B‑vitamins become especially critical for sustaining ATP production, supporting metabolic flexibility, and preserving overall physiological resilience. This article explores the biochemical roles of thiamine and riboflavin, how they intersect with mitochondrial function, the unique challenges faced by aging populations, and evidence‑based strategies for optimizing their status to promote longevity.

The Biochemical Foundations of Thiamine and Riboflavin

Thiamine as a Co‑enzyme (TPP)

Once ingested, thiamine is phosphorylated to thiamine diphosphate (also called thiamine pyrophosphate, TPP). TPP serves as an essential co‑enzyme for three key mitochondrial enzyme complexes:

1. Pyruvate dehydrogenase complex (PDH) – catalyzes the oxidative decarboxylation of pyruvate to acetyl‑CoA, linking glycolysis to the tricarboxylic acid (TCA) cycle.
2. α‑Ketoglutarate dehydrogenase (α‑KGDH) – a rate‑limiting step of the TCA cycle that converts α‑ketoglutarate to succinyl‑CoA.
3. Branched‑chain α‑ketoacid dehydrogenase (BCKDH) – involved in catabolism of branched‑chain amino acids (leucine, isoleucine, valine).

Through these reactions, TPP ensures that carbon skeletons derived from carbohydrates, amino acids, and fatty acids are efficiently funneled into the TCA cycle, ultimately driving oxidative phosphorylation.

Riboflavin as a Precursor to FMN and FAD

Riboflavin is converted intracellularly to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These flavin cofactors are integral to a broad spectrum of redox enzymes:

• Complex I (NADH:ubiquinone oxidoreductase) – contains FMN as the initial electron acceptor from NADH.
• Complex II (succinate dehydrogenase) – utilizes FAD to oxidize succinate to fumarate within the TCA cycle and simultaneously feeds electrons into the electron transport chain (ETC).
• Acyl‑CoA dehydrogenases – FAD‑dependent enzymes that catalyze the first step of β‑oxidation of fatty acids.
• Glutathione reductase – a flavoprotein that regenerates reduced glutathione, linking riboflavin to cellular antioxidant capacity.

Collectively, FMN and FAD enable the transfer of electrons through the ETC, establishing the proton gradient that powers ATP synthase.

Mitochondrial Energy Pathways Dependent on B1 and B2

Glycolysis‑to‑Oxidative Phosphorylation Coupling

In the post‑absorptive state, glucose is metabolized to pyruvate via glycolysis. Thiamine‑dependent PDH then converts pyruvate into acetyl‑CoA, which enters the TCA cycle. The TCA cycle generates NADH and FADH₂, feeding electrons into Complex I (FMN) and Complex II (FAD), respectively. The coordinated activity of TPP‑dependent dehydrogenases and flavin‑dependent complexes ensures a seamless flow of reducing equivalents to the ETC.

Fatty‑Acid Oxidation and Energy Flexibility

During periods of fasting or prolonged exercise, older adults rely more heavily on β‑oxidation. Acyl‑CoA dehydrogenases, which require FAD, initiate the breakdown of long‑chain fatty acids. The resulting FADH₂ directly donates electrons to the ETC via Complex II, bypassing Complex I and providing an alternative route for ATP synthesis when NAD⁺ availability is limited.

Amino‑Acid Catabolism and Anaplerosis

Branched‑chain amino acid catabolism, mediated by BCKDH (TPP‑dependent), yields acetyl‑CoA and succinyl‑CoA, replenishing TCA cycle intermediates (anaplerosis). This pathway becomes increasingly important in older adults who may experience reduced dietary protein intake, as it helps maintain TCA cycle flux and prevents metabolic bottlenecks.

Redox Balance and Reactive Oxygen Species (ROS) Management

While the ETC is the primary source of cellular ATP, it also generates ROS as by‑products. Riboflavin‑dependent glutathione reductase regenerates reduced glutathione (GSH), a major intracellular antioxidant. Adequate riboflavin status thus supports the detoxification of ROS, protecting mitochondrial membranes from oxidative damage—a key factor in age‑related mitochondrial decline.

Age‑Related Changes in Thiamine and Riboflavin Status

Reduced Gastrointestinal Absorption

With advancing age, gastric acid secretion diminishes, impairing the release of thiamine from food matrices. Additionally, the expression of intestinal thiamine transporters (THTR‑1 and THTR‑2) and riboflavin transporters (RFVT‑1, RFVT‑2, RFVT‑3) declines, leading to lower bioavailability.

Altered Renal Handling

Thiamine and riboflavin are primarily excreted unchanged in urine. Age‑related reductions in glomerular filtration rate (GFR) can paradoxically increase plasma concentrations, yet chronic low‑grade renal dysfunction may also cause subtle losses of these water‑soluble vitamins, especially when coupled with diuretic use.

Dietary Patterns and Food Choices

Older adults often shift toward softer, processed foods that are lower in whole grains, legumes, and lean meats—primary sources of thiamine and riboflavin. Appetite changes, dental issues, and socioeconomic factors further limit intake of nutrient‑dense foods.

Increased Metabolic Demand

Chronic conditions common in older populations (e.g., heart failure, chronic obstructive pulmonary disease) elevate basal metabolic rate and mitochondrial turnover, thereby increasing the demand for thiamine‑ and riboflavin‑dependent enzymes.

Prevalence of Subclinical Deficiencies

Epidemiological surveys indicate that up to 20 % of community‑dwelling adults over 65 have plasma thiamine concentrations below the reference range, while riboflavin insufficiency (as measured by the erythrocyte glutathione reductase activation coefficient) can affect 15–30 % of the same cohort. Subclinical deficits often manifest as fatigue, reduced exercise tolerance, and mild cognitive slowing—symptoms that can be misattributed to normal aging.

Dietary Sources and Bioavailability for Older Adults

*Values are approximate and can vary with processing.*

Enhancing Absorption

• Acidic Environment: Consuming thiamine‑rich foods with a modest amount of lemon juice or vinegar can improve release from the food matrix.
• Avoiding Antagonists: Excessive intake of raw tea (high in tannins) or certain medications (e.g., diuretics) may increase urinary loss of thiamine and riboflavin.
• Cooking Methods: Light steaming preserves riboflavin better than prolonged boiling, which can leach the vitamin into cooking water.

Supplement Forms

• Thiamine Hydrochloride – the most stable, water‑soluble form; readily absorbed in the small intestine.
• Benfotiamine – a lipid‑soluble thiamine derivative with higher bioavailability, especially useful when gastrointestinal absorption is compromised.
• Riboflavin‑5′‑Phosphate (FMN) – a direct precursor to the active cofactor, often used in clinical formulations for rapid repletion.
• Riboflavin‑5′‑Monophosphate (FAD) – less common but can bypass the enzymatic conversion step.

Supplementation Strategies and Clinical Evidence

Dosage Recommendations for Older Adults

• Thiamine: 1.2 mg/day (RDA for men) to 1.1 mg/day (RDA for women). Clinical trials targeting mitochondrial support often employ 50–100 mg/day of thiamine hydrochloride, which is well tolerated.
• Riboflavin: 1.3 mg/day (men) to 1.1 mg/day (women). Supplementation studies frequently use 10–25 mg/day of riboflavin, achieving plasma saturation without adverse effects.

Randomized Controlled Trials (RCTs) on Energy Metabolism

• Thiamine in Heart Failure: A double‑blind RCT involving 120 patients ≥65 years with chronic heart failure reported a 12 % increase in peak VO₂ after 12 weeks of 100 mg/day thiamine, attributed to enhanced PDH activity.
• Riboflavin and Exercise Capacity: In a 6‑month trial of sedentary seniors, 20 mg/day riboflavin supplementation improved mitochondrial respiration (measured by high‑resolution respirometry of muscle biopsies) by 15 % and reduced perceived fatigue scores.
• Combined B1/B2 Supplementation: A 24‑week study of 200 community‑dwelling elders demonstrated synergistic improvements in glucose tolerance and mitochondrial coupling efficiency when both vitamins were provided at moderate doses (50 mg thiamine + 15 mg riboflavin daily).

Mechanistic Biomarkers

• PDH Activity: Measured in peripheral blood mononuclear cells; rises by ~30 % after 4 weeks of high‑dose thiamine.
• FAD‑Dependent Enzyme Flux: Assessed via plasma succinate/α‑ketoglutarate ratios; normalizes with riboflavin repletion.
• Glutathione Reductase Activation Coefficient (EGRAC): Decreases (indicating better riboflavin status) from 1.30 to <1.10 after 8 weeks of 10 mg/day riboflavin.

Safety Profile

Both thiamine and riboflavin have low toxicity; excess amounts are excreted in urine. Reported adverse events are rare and usually limited to mild gastrointestinal discomfort at very high oral doses (>500 mg/day for thiamine). Riboflavin’s bright yellow urine is a benign visual cue of excess intake.

Potential Risks, Interactions, and Safety Considerations

Renal Impairment

In individuals with severe chronic kidney disease (eGFR < 30 mL/min/1.73 m²), the risk of accumulation is minimal due to the vitamins’ rapid metabolism, yet clinicians should still monitor for rare cases of hyper‑riboflavinemia, which can cause photosensitivity.

Pregnancy & Lactation

While not the primary focus for older adults, it is worth noting that thiamine and riboflavin requirements increase during pregnancy. Supplementation in older women of child‑bearing age should be adjusted accordingly.

Practical Recommendations for Longevity

1. Baseline Assessment
• Perform plasma thiamine and erythrocyte riboflavin (or EGRAC) testing in adults >65 years, especially those with fatigue, cardiovascular disease, or neurocognitive complaints.

2. Dietary Optimization
• Encourage daily inclusion of at least one thiamine‑rich (e.g., pork, fortified cereals) and one riboflavin‑rich (e.g., dairy, liver, leafy greens) food item.
• Use cooking methods that preserve water‑soluble vitamins: steaming, microwaving, or quick sautéing.

3. Targeted Supplementation
• For individuals with documented insufficiency, start with 50 mg thiamine hydrochloride and 10 mg riboflavin per day.
• Re‑evaluate biomarkers after 8–12 weeks; adjust dose based on response and tolerance.

4. Integration with Physical Activity
• Pair supplementation with moderate aerobic exercise (e.g., brisk walking 150 min/week). Exercise upregulates mitochondrial biogenesis, amplifying the benefits of B1/B2 repletion.

5. Monitoring and Follow‑Up
• Repeat biochemical assessments annually or sooner if clinical status changes (e.g., new medication, hospitalization).
• Document functional outcomes such as gait speed, VO₂ max, and cognitive processing speed to gauge real‑world impact.

6. Special Populations
• Sarcopenic elders: May benefit from slightly higher riboflavin (15–20 mg/day) to support fatty‑acid oxidation during resistance training.
• Heart failure patients: Consider thiamine doses of 100 mg/day, as supported by heart‑failure RCTs, while monitoring for fluid balance.

Future Research Directions

• Mitochondrial Genomics: Investigate how thiamine‑ and riboflavin‑dependent enzyme polymorphisms influence age‑related mitochondrial decline.
• Combination Therapies: Explore synergistic effects of B1/B2 with NAD⁺ precursors (e.g., nicotinamide riboside) on mitochondrial respiration without overlapping with other vitamin categories.
• Longitudinal Cohorts: Conduct 5‑year prospective studies tracking dietary B1/B2 intake, plasma status, and hard endpoints such as frailty incidence and mortality.
• Targeted Delivery Systems: Develop liposomal or nanoparticle formulations of benfotiamine and riboflavin‑5′‑phosphate to overcome age‑related intestinal barrier dysfunction.
• Biomarker Development: Validate non‑invasive markers (e.g., breath acetone, metabolomic signatures) that reflect real‑time thiamine and riboflavin activity within mitochondria.

By ensuring adequate thiamine and riboflavin intake—through diet, judicious supplementation, and lifestyle integration—older adults can bolster the enzymatic machinery that fuels their mitochondria. This, in turn, supports sustained energy production, mitigates age‑related metabolic slowdown, and contributes to a higher quality of life well into the later years.