Concept:Vitamin B1 Thiamine and TrPs

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Vitamin B₁ (thiamine) is an essential water-soluble vitamin whose primary biological role is in the oxidative metabolism of glucose. It is the vitamin most directly linked to the energy crisis at the heart of myofascial trigger point (TrP) pathophysiology. Thiamine insufficiency increases the susceptibility of muscles to TrPs that are resistant to local therapy until the serum thiamine level is raised to the mean normal level or above.

Thiamine has been relatively unexplored in relation to myofascial pain syndromes, yet it is considered potentially important because it is essential for the oxidative metabolism of glucose that leads to the production of pyruvate — the molecule at the gateway to the Krebs cycle and to ATP synthesis. Since an energy crisis is a key link in the chain of histochemical changes characteristic of TrPs, anything that interferes with the energy supply of the muscle will aggravate TrPs.

Discovery and History

In 1884, Takaki of Japan decreased the disastrous incidence of beriberi in the Japanese navy by adding meat, vegetables and condensed milk to the rice diet of the sailors. By 1912, the therapeutic effectiveness of rice polishings had been demonstrated. In 1936, Williams and his coworkers announced the chemical structure and synthesis of the active principle, thiamine.

The disease beriberi — its name deriving from a Sinhalese word meaning extreme weakness — had been the scourge of Asian populations dependent on polished white rice, stripping away the germ and bran where thiamine is concentrated. The demonstration that a single dietary factor could eliminate a devastating neurological and cardiac syndrome was a founding event of nutritional biochemistry.

Biochemical Functions

The active form of vitamin B₁ in the body is thiamine pyrophosphate (TPP), also known as thiamine diphosphate (TDP).

TPP is an essential coenzyme in three critical enzyme complexes:

  1. Pyruvate dehydrogenase — converts pyruvate to acetyl-CoA, which enters the Krebs citric acid cycle. Without TPP, pyruvate accumulates and the cell cannot proceed to oxidative phosphorylation. This is the rate-limiting step for glucose-derived energy in aerobic metabolism.
  2. α-ketoglutarate dehydrogenase — a second Krebs cycle reaction requiring TPP. Blockade here impairs the full citric acid cycle.
  3. Transketolase — a key enzyme of the anaerobic glycolytic pathway (pentose phosphate pathway); thiamine is therefore a coenzyme for transketolase, essential for normal energy production within the cell.

TPP is therefore essential for:

  • Normal energy production at the cellular level
  • The energy crisis that is part of the pathophysiology of a TrP (see Chapter 2, Part D of the source volume)
  • Normal nerve function — neuropathy can be a significant factor in the development of myofascial TrPs. These issues urgently need well-designed research.
  • Synthesis of neurotransmitters
  • Normal thyroid hormone function: thiamine seems to potentiate the effectiveness of thyroid hormone; both are essential to energy metabolism. Patients with low thiamine levels given thyroid supplement may develop symptoms of excess thyroid hormone — the dose of thyroid supplement must be reduced once the thiamine deficiency is corrected

Thiamine and Thyroid Function

The interaction between thiamine and thyroid hormone is clinically important. In the presence of thiamine insufficiency, even a small dose of thyroid hormone may precipitate symptoms of acute thiamine deficiency, which in some respects mimics thyrotoxicosis and may be misinterpreted as intolerance to the thyroid medication. After the thiamine deficiency has been corrected, the same small dose, and often larger doses, of thyroid hormone are well tolerated. Conversely, thiamine insufficiency patients already taking thyroid supplement who receive sufficient thiamine to correct a deficiency of that vitamin may then develop symptoms of excess thyroid hormone, and the dose of thyroid supplement must be reduced.

Insufficiency and Deficiency in the Context of Myofascial Pain

Thiamine insufficiency is indicated by a low normal, or marginally abnormal, serum thiamine level. The muscles of these patients have increased susceptibility to TrPs that are resistant to local therapy until the serum thiamine level is raised.

Clinically, thiamine insufficiency can be detected by the presence of peripheral neuropathy, characterised by:

  • Diminished distal pain and temperature perception in the legs and feet
  • Loss of vibration sense
  • Loss of ankle tendon reflexes (not necessarily present in mild sensory neuropathy)

Some thiamine-inadequate and many thiamine-deficient patients have:

  • Nocturnal calf cramps
  • Mild dependent oedema
  • Constipation, fatigue
  • Decreased vibratory perception in relation to nerve fibre length

When given thiamine parenterally, these patients may promptly lose several pounds by diuresis (the body ceases retaining fluid to supply the oedema), have softer stools, and are relieved of nocturnal calf cramps.

In contrast to the painful calf cramps sometimes associated with thiamine deficiency, painless contractions of the hand or other muscles may be due to a lack of pantothenic acid, and relieved by its oral supplementation. Tinnitus may be relieved by a combination of thiamine and niacin therapy, but not by one vitamin alone if both are low.

Thiamine Deficiency and Alcohol

The abuse of alcohol can lead to signs and symptoms that are a variable composite of three diseases: alcoholism, thiamine deficiency, and liver dysfunction. Not only is the diet of the alcoholic likely to be deficient in thiamine, but the intake of ethyl alcohol seriously reduces thiamine absorption in either the presence or absence of liver disease. The liver disease itself can severely impair the conversion of ingested thiamine to its active form, aggravating the thiamine deficiency. Of 43 alcoholic patients who showed enzyme evidence of thiamine deficiency, 74% also had gait and oculomotor disturbances; the others did not.

Laboratory Tests

Tests for thiamine include:

  • Chemical identification
  • Microbiologic assay
  • Erythrocyte transketolase (ETK) activity — historically used, but now considered an inadequate method as it is less sensitive than HPLC, has poor precision, and has specimen stability concerns. Its use has been supplanted by direct measurement.
  • Whole blood or erythrocyte HPLC for thiamine diphosphate (TDP) — the active form of vitamin B₁; this is the preferred current method. Reference values (fasting): 70–180 nmol/l. A TDP level below 70 nmol/l suggests deficiency.
  • Blood levels of pyruvate and α-ketoglutarate: the fasting blood pyruvate is elevated above 1.0 mg/dl in thiamine deficiency. Following ingestion of glucose, serum pyruvate peaks in nearly 1 hour due to the disturbed glycogenesis — this is a more specific indicator of thiamine deficiency than increased serum α-ketoglutarate.
  • Lactobacillus viridescens is the most widely employed microbiologic test organism; the phytoflagellata Ochromonas danica appears to be the most sensitive indicator of thiamine deficiency, especially in the presence of severe liver disease.

Requirements and Sources

The need for thiamine is directly related to caloric intake when this corresponds to energy expenditure. Recommended daily allowances (RDA) by age group:

  • Infants 0–12 months: 0.2–0.3 mg/day
  • Children 1–8 years: 0.5–0.6 mg/day
  • Children 9–13 years: 0.9 mg/day
  • Ages 14–18 years: 1.0–1.2 mg/day
  • Adults ≥19 years: 1.1–1.2 mg/day
  • Pregnant and lactating women: 1.4 mg/day

The RDA is increased for pregnant and lactating women. Normal thiamine reserves usually provide at least 5 weeks of protection from severe thiamine deprivation.

Food Sources

Thiamine is widely distributed in both animal and vegetable foods, but few foods are rich in it. Best sources:

  • Lean pork (the richest common food source)
  • Beans, nuts, and certain whole grain cereals
  • Kidney, liver, beef, eggs, and fish

In cereal grains, the vitamin is present almost exclusively in the germ and hull. Since these are lost in milling and refining, processed grains need to have the thiamine replaced.

Factors That Destroy or Impair Thiamine

  • Heat — thiamine can be destroyed by heating above 100°C (212°F); it is quickly leached out of foods during washing or boiling; degraded rapidly in foods fried in a hot pan or cooked under pressure; rapidly degraded in an alkaline medium
  • Canned vegetables generally contain only about 30% of the thiamine initially available
  • Retention in preprocessed meats ranges from 40–85%; increasing the roasting temperature of beef or pork reduces thiamine content from 62–51% of the original
  • Pasteurisation of cow's milk destroys from 3–10% of its thiamine; additional heat in processing evaporated milk reduces its thiamine by 30%
  • Bracken fern — grows in upland pastures where it can pose a hazard to foraging animals; destroyed by vitamin B₁ by a thiaminase enzyme
  • Alcohol — seriously reduces thiamine absorption; excretion of thiamine is potentiated by diuretics and by regularly drinking large amounts of water
  • Tea and gastric alkalinisers — tannic acid in tea, and also antacids, taken with food impair thiamine absorption
  • Conversion of dietary and synthetic thiamine to thiamine pyrophosphate, the physiologically active form, is seriously compromised in liver disease

Bioavailability

  • Impaired by alcohol ingestion, magnesium deficiency, tannic acid (tea), antacids, and diuretics
  • Excretion is potentiated by diuretics and by drinking large amounts of water, which causes a diuresis

Therapy

Thiamine is available over-the-counter in 10-, 50- and 100-mg tablets. It is also available for injection at a concentration of 100 mg/ml.

Oral therapy:

  • The therapeutic oral dose usually recommended is 10 mg daily for several weeks, or until all evidence of deficiency has disappeared
  • Increasing this to 50 mg daily will cause no harm and will ensure providing for patients with an exceptional need for the vitamin
  • A B-50 vitamin supplement contains 50 mg of thiamine and is an ample daily dose to protect nearly all individuals from thiamine insufficiency — it can be taken indefinitely as a safe, inexpensive form of health insurance

Parenteral therapy (for established deficiency or malabsorption):

  • 100 mg three times daily intravenously for several days, followed by 100 mg/day orally until complete recovery
  • Infantile beriberi: 5–20 mg intravenously
  • Biweekly intramuscular injections of 100 mg for 3–4 weeks bring serum concentration to an optimal level in patients with poor intestinal absorption or exceptional need

Toxicity

When taken in much larger amounts, excess thiamine is excreted in the urine and has no reported human toxicity. Intolerance to oral thiamine is extremely rare; daily doses of 500 mg have been administered for as long as a month without ill effects. However, in rare instances, intravenous thiamine has produced fatal anaphylactic shock. Most of these reactions occurred in patients who had previously received large doses of thiamine by injection — they apparently developed sensitivity to additives in the injected solution.

In one study, increasing an oral intake of thiamine above 10 mg altered neither its blood level nor the amounts excreted in the urine, supporting the belief that intestinal absorption was likely the limiting step.

The Biology of Starvation: Thiamine

In starvation or severe caloric restriction, thiamine deficiency emerges with characteristic urgency because the body has no significant storage depot for this vitamin (normal reserves last only about 5 weeks). The timeline of thiamine depletion illustrates the relationship between nutrient availability and neurological function:

  • Thiamine is consumed in proportion to caloric expenditure, specifically carbohydrate metabolism
  • In glucose-overloaded states (refeeding syndrome with excessive glucose after starvation, or overloading thiamine-depleted tissues with glucose), acute Wernicke's encephalopathy can be precipitated — the brain, with its absolute dependence on glucose oxidation, is catastrophically vulnerable
  • Wet beriberi (high-output cardiac failure with oedema) reflects the dependence of myocardial contractility on pyruvate dehydrogenase activity; without TPP, the heart cannot efficiently generate ATP and begins to fail at high-output, then low-output states
  • Dry beriberi (peripheral sensorimotor neuropathy) reflects the dependence of axonal transport and myelin maintenance on thiamine-dependent energy metabolism
  • Wernicke-Korsakoff syndrome (ophthalmoplegia, ataxia, confusion, and amnesia) represents the selective vulnerability of certain brainstem and diencephalic neurons to thiamine deficiency, mediated by the intense requirement of those neurons for oxidative glucose metabolism

The evolutionary logic is that starvation produces caloric deficit before thiamine deficit; but when dietary thiamine is low while caloric intake is maintained (polished rice diet, alcohol-displaced diet), the metabolic machinery runs down without the warning of starvation — a biochemical ambush that beriberi represents.

In the context of myofascial pain, this biology implies that any state of chronic partial caloric restriction, selective food avoidance, excessive alcohol, malabsorption, or high metabolic demand (illness, pregnancy, lactation) places a patient in a zone of thiamine insufficiency that directly aggravates TrP irritability, even when serum levels remain within the "normal" range.

References

  • Travell JG, Simons DG. Myofascial Pain and Dysfunction: The Trigger Point Manual, Volume 1. 2nd ed. Baltimore: Williams & Wilkins; 1999. Chapter 4, Section C.
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