Chronic fatigue: 8 deficiencies no one screens for

Why deficiencies multiply, even among people who eat well

The observation is documented and reproducible: the concentration of vitamins, minerals and trace elements in fruits and vegetables has decreased by 20 to 80% over half a century, depending on the nutrient and variety. The work of Anne-Marie Mayer (1997, 2022) and that of Fan et al. (2008) on wheat measured it food by food, over decades. Soils are becoming impoverished; varieties selected for their yield are rarely selected for their nutritional density.

This is not a question of individual willpower. An exemplary 2025 dietary model — rich in quality proteins, two plates of varied vegetables per day, fatty fish, legumes, oilseeds — still shows deficits of between 19 and 72% compared with an ordinary peasant day in 1940, according to our internal food-by-food micronutritional comparison (CIQUAL 2020, Mayer 1997/2022 decline coefficients). Eating better reaches its limits when the foods themselves contain less.

Here are the eight most frequently encountered deficits, their consequences on physiology, and why they often escape standard panels.

1. Magnesium — the deficit of modern civilisation

Magnesium intervenes in more than 300 enzymatic reactions: ATP production, nerve transmission, muscle contraction, DNA synthesis, blood-sugar regulation, hormonal balance. Its presence even conditions the conversion of vitamin D into its active form — meaning that vitamin D supplementation without sufficient magnesium can paradoxically prove counter-productive.

The usual signs of a subclinical deficit are rarely connected to their cause: night cramps, an eyelid twitching spasmodically, irritability, non-restorative sleep, anxiety, persistent fatigue despite sufficient rest. This clinical picture, omnipresent in consultations, is statistically linked to insufficient magnesium status.

The structural reason: industrial food is impoverished in magnesium, and chronic stress increases urinary losses. Average requirements are around 360 to 420 mg per day depending on body weight; most dietary surveys in Europe show real intakes below 250 mg.

A note on forms: magnesium oxide, the ubiquitous form in entry-level supplements, has a bioavailability of barely 4%. Citrate and bisglycinate exceed 40% absorption with better digestive tolerance. The chosen form entirely conditions the real effectiveness of the supplementation.

2. Iodine — the underfed thyroid gland

Iodine is the indispensable constituent of thyroid hormones T3 and T4, which regulate basal metabolic rate, thermogenesis, neurological development, bone growth and cellular differentiation. The WHO still classifies iodine deficiency as one of the main causes of preventable mental retardation in the world.

In Switzerland and across much of Europe, iodised-salt policy has attenuated severe forms of the deficiency but has not eliminated subclinical forms.

A moderate iodine deficit translates into a slowed thyroid function: fatigue, sensitivity to cold, unexplained weight gain, hair loss, cognitive fog, slowed transit. These symptoms are often attributed to other causes, in particular because standard TSH screening remains normal in early stages.

An important biochemical point: selenium and zinc are also indispensable to the conversion of T4 to active T3 via deiodinases — selenium-dependent enzymes. A deficiency in selenium and zinc could thus disturb thyroid function even in the presence of sufficient iodine intake. These micronutrients must be considered jointly.

3. Iron — the most common deficiency, the worst corrected

Iron deficiency is the most widespread in the world according to the WHO, and it remains one of the most poorly managed in routine practice. It cannot be reduced to anaemia: well before haemoglobin drops, ferritin — the indicator of reserves — collapses, with measurable consequences on cognitive functions, exercise tolerance, thermal regulation and hair quality.

Haem iron, from meat and fish, is absorbed at 15-35%. Non-haem iron, present in plants and eggs, shows an absorption of 2 to 10% under standard conditions. Vitamin C significantly improves this absorption by reducing ferric iron (Fe³⁺, poorly soluble) to ferrous iron (Fe²⁺, actively transported by the enterocyte's DMT-1).

An often-ignored point: iron, zinc and copper share the same intestinal transporter DMT-1. Administered simultaneously and at high concentrations, they compete for the same absorption sites. This is one of the biochemical reasons that justifies not including them together in the same multivitamin supplement: mutual inhibition can reach 40% or more depending on proportions and galenic form.

Women of childbearing age, endurance athletes and regular blood donors constitute the most exposed populations.

4. The B-vitamin complex — an ecosystem, not isolated molecules

B-group vitamins are not interchangeable, but they are profoundly interdependent. They share common metabolic pathways — Krebs cycle, mitochondrial respiratory chain, methylation cycle — and their clinical effectiveness is amplified when the complex is complete. An isolated B12 deficit, for example, hinders the methylation cycle as much as a combined B9 or B6 deficit.

Vitamin B12 — the deficit that masks itself for years

B12 hepatic reserves allow a clinical picture to settle in only three to five years after intake ceases, making screening late. Deficiency entails progressive demyelination, megaloblastic anaemia, hyperhomocysteinaemia — an independent cardiovascular and cognitive risk factor — and memory disturbances. Vegan populations and people over 60 (decreased absorption due to reduced gastric intrinsic factor) are particularly concerned.

Vitamin B9 (Folate) — the mutation no one knows about

Folic acid administered in classical supplementation must be converted to 5-MTHF by the MTHFR enzyme. However, 30 to 50% of the population carries a mutation of the MTHFR gene (C677T polymorphism) that drastically reduces this conversion. For these individuals, supplementation with folic acid alone remains poorly effective: only the already-methylated form, 5-MTHF, is directly assimilable independently of MTHFR status. The consequences of an active folate deficiency include depression, cognitive disorders, neural tube malformation risks and hyperhomocysteinaemia.

Vitamins B1, B2, B3, B5, B6, B8 — the energy backbone

Thiamine (B1) catalyses the entry of pyruvate into the Krebs cycle; riboflavin (B2) supplies FAD to complexes I and II of the respiratory chain; niacin (B3) is the precursor of NAD⁺, cofactor of more than 400 enzymatic reactions; pantothenic acid (B5) constitutes acetyl-CoA; pyridoxine (B6) conditions the synthesis of dopamine, serotonin and GABA; biotin (B8) supports glycogenesis and keratinisation. A deficit in any of these links translates into a drop in ATP production: fatigue is its first and most constant expression.

Consumers of coffee, tea or alcohol have increased thiamine needs, the molecule being degraded or its absorption inhibited by these substances. Chronic stress increases needs for vitamins B5 and B6 via the adrenal axis.

5. Vitamin D — the hormone we think we know

Vitamin D is not strictly speaking a vitamin: it is a hormonal precursor, synthesised in the skin under the action of B-ultraviolets, then converted to calcitriol (1,25-dihydroxyvitamin D) in the kidney. It acts via nuclear receptors present in almost all tissues and regulates the expression of several hundred genes. Its role in calcium absorption is known; its involvement in immune regulation, mood balance, muscle function and cardiovascular protection is today also documented.

At European latitudes, cutaneous synthesis is insufficient from October to March. A large fraction of the population shows serum 25-OH-vitamin D levels below 30 ng/mL, the threshold below which clinical effects of the deficiency become measurable. Autumnal and winter fatigue, recurring ENT infections, low mood, diffuse muscle pain: all signs that invite an evaluation of this status.

Synergy to remember: magnesium is the indispensable cofactor for the conversion of vitamin D into its active form. Insufficient magnesium status limits the effectiveness of any vitamin D supplementation, however well dosed. This point is rarely mentioned in routine consultations.

6. Zinc — the silent cofactor of immunity and reproduction

Zinc is a cofactor of about 300 enzymes. It conditions the structure and activity of zinc-finger proteins (transcription factors), regulates T and NK lymphocytes, participates in insulin release, in spermatogenesis, in DNA synthesis and in cell membrane protection via Cu/Zn superoxide dismutase.

Its deficiency is particularly frequent in those under prolonged antibiotic therapy. Clinical signs associate white spots on the nails, taste and smell disorders, hair loss, slow healing, immune depression and, in men, decreased sperm quality.

An antagonism to know: an excess of zinc reduces copper absorption via the same intestinal transporter. This is why orthomolecular formulations do not dose zinc at excessive levels. The Zn/Cu ratio recommended in the literature lies between 8 and 10 to 1. The inclusion of copper in the same supplement is however not automatically the solution: at high concentrations and in aqueous solution, the two minerals mutually inhibit themselves on DMT-1, reducing the absorption of both.

7. Selenium — a trace element whose soil is emptying

Selenium is the cofactor of glutathione peroxidases (GPx), major antioxidant enzymes of endogenous cellular defence. GPx4, in particular, neutralises membrane lipid peroxides and prevents a cell-death mechanism called ferroptosis, implicated in numerous chronic pathologies. Deiodinases, other selenoenzymes, convert T4 to active T3: selenium is thus directly linked to thyroid function.

European soils, particularly in Finland, Switzerland and much of central Europe, are naturally poor in selenium. Plants that grow there therefore contain little, independent of agricultural quality. Average dietary intake in Europe struggles to reach recommendations (55 to 70 μg/day according to EFSA).

The form matters here too: L-selenomethionine, the organic form present in vegetable proteins, is absorbed at more than 90% and integrates directly into endogenous proteins. Sodium selenite, the inorganic form, shows limited absorption (around 25%), without toxicity at usual doses but with lesser functional effectiveness.

8. Vitamin C — much more than a cold remedy

Ascorbic acid is a cofactor of more than ten hydroxylases, including the prolyl- and lysyl-hydroxylases indispensable to collagen synthesis — each collagen molecule requires it in stoichiometric quantity. It is also the unique catalyst for the conversion of dopamine to noradrenaline (dopamine-β-hydroxylase) and conditions the synthesis of adrenaline: each adrenaline molecule produced consumes one vitamin C molecule. In periods of chronic stress, adrenal reserves collapse rapidly.

Vitamin C is the only water-soluble antioxidant capable of regenerating oxidised vitamin E in membranes. It potentiates non-haem iron absorption, blocks the formation of carcinogenic nitrosamines and supports immunoglobulin production. It also improves the hepatic conversion of cholecalciferol to 25-hydroxyvitamin D, thus indirectly participating in vitamin D status.

Contrary to a received idea, vitamin C is not systematically covered by contemporary diet. Chronic oxidative stress, tobacco, pollution, recurring infections and intense exercise increase needs well beyond the RDA of 80 mg set to prevent scurvy.

What this article does not replace

The deficits described here are frequent, well documented and clinically significant. They are nonetheless individual in their expression, depth and interactions. An in-depth micronutritional assessment — distinct from standard biological analyses that do not always look for the right markers — is the only way to obtain a precise picture.

If you recognise yourself in several of the pictures described above, I encourage you to consult a health professional trained in micronutrition or orthomolecular medicine: physician, pharmacist, naturopath, dietician or nutritionist with specific training in these fields. An accurate diagnosis always precedes an adequate supplementation solution.

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