| Supplement | Properties | Indications | Dosage | Contraindication | Side Effects | Synergistic Combinations |
|---|---|---|---|---|---|---|
| Coenzyme Q10 (CoQ10) | Essential cofactor in the electron transport chain for ATP production [1,2]. Acts as a powerful antioxidant protecting mitochondrial membranes [3]. Helps transport electrons in oxidative phosphorylation [4]. Supports cellular energy metabolism [5]. | Chronic fatigue syndrome [6,7]. Mitochondrial dysfunction [3]. Heart failure and cardiovascular disorders [8]. Age-related energy decline. Exercise performance enhancement. Migraine prevention [9]. | General health: 100-200 mg/day. Mitochondrial support: 100-300 mg/day [10]. Exercise performance: 300 mg/day [10]. Divide doses if taking >100mg daily Take with meals containing fat for optimal absorption [11]. Morning or afternoon dosing (avoid evening to prevent insomnia). | Hypersensitivity to CoQ10 or excipients. Pregnancy and breastfeeding (insufficient data). Caution with diabetes (may lower blood glucose). Bile duct obstruction. AVOID with Warfarin: Reduces anticoagulant effectiveness. | Generally well-tolerated. Mild insomnia (especially with doses >100mg). Stomach upset, nausea, diarrhea. Headache, dizziness. Skin rash (rare). Liver enzyme elevation at high doses (>300mg). | Acetyl-L-Carnitine: Enhanced mitochondrial function [12]. Alpha-Lipoic Acid: Improved antioxidant protection [12]. PQQ: Complementary mitochondrial biogenesis [13]. Magnesium: Support for ATP synthesis. Resveratrol: Enhanced SIRT1 activation. [14] |
| Acetyl-L-Carnitine (ALC) | Facilitates fatty acid transport into mitochondria for β-oxidation [15]. Supports ATP production and energy metabolism [16,17]. Maintains acetyl-CoA/CoA ratio for metabolic flexibility [15]. Neuroprotective effects and cognitive support [18]. | Chronic fatigue and low energy [19]. Age-related cognitive decline [20]. Peripheral neuropathy [21]. Mitochondrial dysfunction [15-17]. Exercise recovery [22,23]. Alzheimer’s disease support [18,20]. | General support: 500-1000 mg/day [23]. Cognitive support: 1500-3000 mg/day [20]. Exercise performance: 2000-3000 mg/day [23]. Divided into 2-3 doses throughout the day. Take on empty stomach for better absorption. Can be taken with or without food. Morning or early afternoon (may be stimulating). Avoid late evening dosing. | Hypothyroidism (may interfere with thyroid hormone). Seizure disorders (may lower seizure threshold) [24]. Pregnancy and breastfeeding (insufficient data). | Generally well-tolerated. Mild gastrointestinal upset. Nausea, vomiting. Restlessness, insomnia. Fishy body odor (rare). Increased appetite. | Alpha-Lipoic Acid: Enhanced mitochondrial protection [12]. CoQ10: Improved energy production [12]. PQQ: Mitochondrial biogenesis support [13,25,26]. B-vitamins: Enhanced energy metabolism [16]. Magnesium: ATP synthesis support. |
| Pyrroloquinoline Quinone (PQQ) | Promotes mitochondrial biogenesis (creation of new mitochondria) [27]. Potent antioxidant protecting against oxidative stress [13]. Supports mitochondrial function and ATP synthesis [13]. Enhances PGC-1α expression and SIRT3 activation [13, 27-28] | Mitochondrial dysfunction [13]. Age-related fatigue [13,29]. Cognitive decline [13]. Exercise-induced oxidative stress [13]. Metabolic disorders [29]. Sleep quality improvement | Standard dose: 10-20 mg/day [29]. Fatigue/sleep support: 20 mg/day for 8 weeks [29]. Exercise performance: 20 mg/day [29]. Can be taken with or without food. Avoid evening dosing (may be stimulating). Consistent daily timing recommended. | Pregnancy and Breastfeeding: Avoid (insufficient safety data). No other specific contraindications established. | Generally very well-tolerated [30]. Rare mild digestive upset [30]. | CoQ10: Enhanced mitochondrial energy production [13]. NAD+ precursors: Complementary cellular energy pathways [13,28]. Resveratrol: SIRT activation synergy. Alpha-Lipoic Acid: Enhanced antioxidant protection [26]. Creatine: Improved cellular energy buffering. |
| Alpha-Lipoic Acid (ALA) | Cofactor for mitochondrial enzyme complexes (pyruvate dehydrogenase, α-ketoglutarate dehydrogenase) [31]. Universal antioxidant (both water and fat-soluble) [31]. Supports glucose metabolism and insulin sensitivity. Promotes mitochondrial biogenesis [32]. | Mitochondrial dysfunction [31]. Diabetic neuropathy [31]. Age-related mitochondrial decline [31]. Oxidative stress [31]. Metabolic syndrome [31]. Chronic fatigue. | General support: 300-600 mg/day [31,32]. Diabetic neuropathy: 600-1800 mg/day [32]. Mitochondrial support: 50-200 mg/day (primary mitochondrial disorders) [31]. Seniors: Stay at lower range (300-600 mg/day) [31,32]. Take on empty stomach for better absorption, 30-60 minutes before meals [31,32]. Morning or early afternoon dosing | Thiamine deficiency (may worsen) [32]. Caution with diabetes medications [32]. Pregnancy and breastfeeding (insufficient data) [32]. | Mild gastrointestinal upset [32]. Nausea, stomach discomfort [32]. Skin rash (rare). Metallic taste. Hypoglycemia (monitor blood sugar) [32]. | Acetyl-L-Carnitine: Enhanced mitochondrial protection [12]. CoQ10: Improved antioxidant status [12]. Vitamin E: Antioxidant regeneration [32]. Vitamin C: Enhanced antioxidant network [32]. B-complex: Energy metabolism support. |
| NAD+ Precursors (NMN/NR) | Increase cellular NAD+ levels for energy metabolism [33,34]. Support SIRT1/3 activation and mitochondrial function [35]. Enhance DNA repair and cellular stress resistance [33]. Promote mitochondrial biogenesis and dynamics [35]. | Age-related energy decline [33,35]. Mitochondrial dysfunction [35]. Neurodegenerative diseases [36]. Metabolic disorders [35]. Cellular aging [33,35]. Cognitive decline [37,38]. | NMN: 250-1000 mg/day [37,38]. NR: 100-1000 mg/day [37,38]. Start with lower doses and increase gradually [37,38]. Morning dosing preferred, can be taken with or without food [37,38]. Consistent timing important | Pregnancy and breastfeeding (insufficient data) [33]. Cancer patients (theoretical concern about cell proliferation) [33]. No specific contraindications established. | Generally well-tolerated [34,38]. Mild nausea (rare) [34,38]. Flushing (rare) [34,38]. No significant adverse effects in human trials. Long-term safety still being studied. | Resveratrol: Enhanced SIRT1 activation [33,35]. PQQ: Complementary mitochondrial support [13,28]. CoQ10: Improved electron transport [34,35]. Pterostilbene: Enhanced longevity pathways [38]. Magnesium: NAD+-dependent enzyme support [33]. |
| D-Ribose | Direct substrate for ATP synthesis via pentose phosphate pathway [39]. Bypasses rate-limiting steps in ATP production [40]. Supports rapid ATP recovery after depletion [39,40]. Essential component of nucleotide synthesis [39]. | Heart failure and cardiac dysfunction [39,40]. Chronic fatigue syndrome [39,40]. Fibromyalgia [39,40]. Post-exercise recovery [39,40]. Mitochondrial energy disorders [39,40]. Athletic performance enhancement [39,40]. | General support: 5-15 g/day [39,40]. Athletic performance: 10-15 g/day [39,40]. Chronic fatigue: 15 g/day [39,40]. Mix powder in non-carbonated liquid, Take within 30 minutes of mixing [40]. Divide into 3 doses throughout the day [40]. Take with food to reduce GI upset. [39,40]. | Diabetes (monitor blood glucose closely) [39,40]. Pregnancy and breastfeeding (insufficient data). Gout (may increase uric acid) [39,40]. | Generally well-tolerated [39,40]. Mild diarrhea, slight nausea, stomach discomfort [39,40]. Hypoglycemia (may lower blood sugar) [39,40]. | CoQ10: Enhanced ATP production [39,40]. Creatine: Improved energy buffering [39,40]. Magnesium: ATP synthesis support [39,40]. B-vitamins: Energy metabolism enhancement [39,40]. Carnitine: Improved fatty acid oxidation [39,40]. |
| Magnesium Malate | Magnesium cofactor for ATP synthesis and energy enzymes [41]. Malic acid supports Krebs cycle energy production [42]. Muscle function and energy metabolism [41]. Less gastrointestinal side effects than other Mg forms [41]. | Chronic fatigue syndrome [41]. Fibromyalgia [43,44] Muscle pain and cramping [42] Energy production support [41,42] Exercise performance [42] Magnesium deficiency [41]. | General support: 100-400 mg elemental magnesium/day [41]. Fibromyalgia: 300-600 mg/day, Start with 100-150 mg and increase gradually [43]. Divide doses if taking >200 mg/day [42]. Take with meals to reduce GI upset. Avoid late evening (may be stimulating). | Kidney disease (risk of toxicity) [41]. Severe heart block [41]. Myasthenia gravis [41]. CAUTION with: Antibiotics, bisphosphonates, diuretics [41]. | Generally well-tolerated [41,44]. Mild GI effects if taken on empty stomach, diarrhea, stomach cramps. May be stimulating if used late in day | D-Ribose: Enhanced Krebs cycle function [41]. CoQ10: ATP synthesis support [41]. B-vitamins: Energy enzyme activation [41]. Calcium: Balanced mineral status [41]. Vitamin D: Improved absorption [41]. |
| Creatine Monohydrate | Rapid ATP regeneration via phosphocreatine system [45]. Cellular energy buffer and sensor [46]. Mitochondrial stabilization and protection [47]. Antioxidant properties and calcium regulation [47]. | Chronic fatigue syndrome [48]. Mitochondrial disorders [49]. Exercise performance [50]. Muscle weakness [47]. Neurodegenerative diseases [47]. Age-related energy decline [47]. | Maintenance: 3-5 g/day [50]. Loading phase (optional): 20 g/day for 5-7 days, then 3-5 g/day [50]. ME/CFS/FM: 4-20 g/day (higher doses may be more effective) [48]. Start low and increase gradually. Mix powder in liquid (poorly water-soluble) [49]. Can be taken anytime, but post-workout may be beneficial [49]. Consistent daily timing recommended [49,50]. | Kidney disease [49]. Safe in children, adults, and elderly [49]. | Generally very safe [49]. Weight gain (water retention) [49]. Mild GI upset with large doses [49]. Rare: Nausea, stomach discomfort [49]. Take gradually to tolerance [49]. | D-Ribose: Enhanced ATP production [39,40]. Protein powder: Improved muscle synthesis [49]. Beta-alanine: Exercise performance [49]. BCAA: Muscle recovery [49]. CoQ10: Mitochondrial energy support [49]. |
| Resveratrol | SIRT1 activation and mitochondrial biogenesis [51]. Promotes PGC-1α activation and gene expression [51]. Antioxidant and anti-inflammatory effects [52,53]. AMPK activation and metabolic enhancement [51]. | Age-related mitochondrial decline [51,54]. Metabolic syndrome [51,52]. Cardiovascular health [51,52]. Neurodegeneration prevention [51]. Exercise performance [51,53]. Longevity support [51,54]. | General health: 100-500 mg/day [55]. Mitochondrial support: 150-500 mg/day, preferred for SIRT1 activation. Take with meals for better absorption, fat-containing meal preferred [56]. Morning or early afternoon dosing [55,56]. Trans-resveratrol form preferred [57]. | Hormone-sensitive conditions [57]. Blood clotting disorders [57]. Surgery (discontinue 2 weeks prior) [57]. Pregnancy and breastfeeding. | Generally well-tolerated [55]. Mild GI upset[55]. Headache, dizziness. May have mild estrogenic effects. | NAD+ precursors: Enhanced SIRT1 activation [51,53]. PQQ: Complementary mitochondrial biogenesis [51]. Quercetin: Enhanced bioavailability and effects [56]. CoQ10: Improved mitochondrial function [51,53]. Curcumin: Anti-inflammatory synergy [57]. |
| L-Citrulline | Nitric oxide precursor via arginine conversion [58]. Supports mitochondrial function through NO signaling [59]. Promotes mitochondrial biogenesis via PGC-1α [59]. Improves blood flow and exercise performance [58,60]. | Exercise performance and endurance [60]. Mitochondrial dysfunction [59]. Cardiovascular health [61]. Muscle fatigue and weakness [59]. Blood flow improvement [61]. Potential heat stress protection [58,59]. | General support: 1.5-5 g/day [60,61]. Exercise performance: 6-8 g (single dose) [60,62]. Endurance: 2.4-6 g/day [60]. Start with lower doses and assess tolerance Take on empty stomach for best absorption [58,60]. 30-60 minutes before exercise for performance, Morning or pre-workout timing [58,60]. | Major interaction with PDE-5 inhibitors (Viagra, Cialis) – risk of hypotension and Nitrates – risk of dangerous blood pressure drop [61]. Moderate caution with Blood pressure medications [61]. Pregnancy and breastfeeding (insufficient data) [61]. Kidney disease [61]. Liver disease [61]. | Generally very well-tolerated [60]. Mild stomach discomfort (rare) [60]. Heartburn (rare) [60]. | Arginine: May compete for absorption (use separately) [61]. Beetroot extract: Enhanced NO production [60]. Citrulline malate: Combines with malic acid benefits [62]. CoQ10: Improved mitochondrial function [59]. Magnesium: Enhanced muscle function [59]. B-vitamins: NO synthesis support [59]. |
General Recommendations
Stacking Considerations
- Start with one supplement at a time to assess tolerance
- Core stack: CoQ10 + Magnesium + D-Ribose
- Advanced stack: Add PQQ + NAD+ precursor + ALA
- Performance stack: Add Creatine + L-Citrulline
Timing Optimization
- Morning: NAD+ precursors, PQQ, ALA, Magnesium Malate
- With meals: CoQ10, Resveratrol
- Pre-workout: L-Citrulline, Creatine
- Anytime: D-Ribose, Acetyl-L-Carnitine
Quality Considerations
- Look for standardized extracts
- Consider bioavailable forms (ubiquinol vs ubiquinone)
- Store properly to maintain potency
Monitoring
- Track energy levels, exercise performance, and sleep quality
- Monitor for side effects, especially GI issues
- Consider periodic lab work for comprehensive assessment
- Adjust doses based on individual response
References
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