Introduction
Thiamine | Vitamin C | Vitamin D | |
---|---|---|---|
Other names | Vitamin B1 | Ascorbic acid | Native forms D3: cholecalciferol D2: ergocalciferol Active form Calcitriol |
Molecular characteristics | Water-soluble | Water-soluble | Fat-soluble |
Formula | C12H17N4OS | C6H8O6 | D3: C27H44O |
Molar mass (g/mol) | 265.35 | 176.12 | D3: 384.64 |
Source | Diet (seeds, legumes, rice, cereals, corns, pork, spinach) | Diet [fruits and vegetables (lost by long cooking)]; supplements | Mainly from skin: synthesis from cholesterol elicited by sun exposure (UVB radiation); diet (fatty fish); supplements |
Excretion | Renal Daily loss with CRRT ± 4-5 mg/day | Renal Daily loss with CRRT ± 70 mg/day | Bile/feces and renal Catabolizing enzymes Daily loss with CRRT unknown |
Risk of deficiency | Poor diet Alcoholism Hypermetabolism Increased loss (CRRT) | Poor diet Oxidative stress: sepsis, ischemia–reperfusion, trauma, burns, CRRT Increased loss (CRRT) | Low sun exposure Comedication Obesity Dark skin Chronic disease Malnutrition |
Stores and time to deficiency | Half-life of 18 days. Stores are rapidly depleted when metabolic demands are high | In otherwise healthy persons, scurvy develops in 4–8 weeks. Stores are rapidly depleted if oxidative stress is high | Half-life of 2–3 weeks Metabolism in acute illness unknown |
Functions | Coenzyme for glucose metabolism, Krebs cycle, generation of ATP, pentose phosphate pathway, NADPH production | Donation of electrons Cofactor/co-substrate Anti-oxidant Anti-inflammatory and immune-promoting actions | Classic: regulation of intestinal calcium absorption Nonclassic: cell-specific regulation of transcriptional activity, inhibition of PTH secretion, promotion of insulin secretion, regulatory action on adaptive and innate immunity, inhibition of cell proliferation, stimulation of differentiation |
Clinical consequences of deficiency | Lactic acidosis Wet beriberi: high-output cardiac failure Dry beriberi: polyneuropathy, muscle weakness, confusion, ataxia, nystagmus Wernicke–Korsakoff encephalopathy | Scurvy Poor wound healing Lassitude, depression Hypotension Capillary leakage Bleeding Infections | Rickets (children) Osteomalacia (adults) Unspecific or absent symptoms Musculoskeletal pain in some cases |
Side effects, toxicity | Unknown | Oxalate nephropathy (ESM) in susceptible persons | Hypercalcemia Acute renal failure Nephrocalcinosis |
Recommended dosea | Healthy persons: 1.5 mg/day Acute critical illness: 100–300 mg/day CRRT: 100 mg/day of therapy to safely compensate effluent losses | Healthy persons: 200 mg/day Acute critical illness: 2–3 g/day iv to correct deficiency (ESM) Chronic critical illness: 0.2–1 g/day? Dialysis/hemofiltration: 0.5–1 g/day Burns: 0.5–1 g/day | Native vitamin D3 or D2 Healthy persons: 600–800 IU/day Risk groups: 1500–2000 IU/day Safe dose: up to 10 000 IU/day Acute critical illness: unknown Dialysis/CRRT: unknown |
Thiamine
Function
Thiamine and acute illness
Dose and future
Vitamin C
Function
Vitamin C and acute illness
Dose and future
Vitamin D
Function
Vitamin D and acute illness
Dose and future
Summary, conclusions and outlook
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The requirements for vitamin C, vitamin D, and thiamine are likely higher in severe illness than in health (ESM).
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The beneficial effect on clinical outcomes will be greater in depleted subjects.
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Determination of thiamine and vitamin C deficiency is not possible without major delay and may be invalidated by improper sampling.
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A better understanding of the role of micronutrients in critical illness may be achievable by means of novel methods including genomics and metabolomics.
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The time is ripe for pragmatic randomized trials in different high-risk populations exhibiting overwhelming oxidative stress using different treatment regimes.