A. Case study
A 24-year-old man visited his general practitioner after he observed what he thought was blood in his urine that persisted for 2 days. The doctor examined him for possible urinary tract infection, renal disease and trauma. He did not have an increased temperature, painful micturition or other pain, malaise of discomfort, or recent significant weight loss. The patient assured his doctor that he felt quite healthy and had not experience any type of trauma recently.

The doctor asked the patient for a urine sample and tested for the presence of blood with a dipstick. The result was negative.

What could be the possible reasons for the test to be negative?

The doctor questioned the patient about consumption of red colorings in, for example, red soft drinks, sweets, etc. The patient denied eating any of these products. The doctor then decided to redo the dipstick test with newer stock and made sure that he used the correct technique. But the result was negative once again. He decided to send a urine sample to a laboratory that would examine it for of red blood cells, but none were detected.

When discussing the case with a colleague, the doctor was asked if he had queried the patient about beetroot, also know as beets. He explained that the ingestion of beetroot could result in the passing of red urine. The doctor said that he ate beetroot regularly and had never experienced this. But the colleague explained that this phenomenon, known as beeturia, occurs only in about 10-14% of people. The doctor questioned his patient and found that he had in fact eaten beetroot on both days in question. The color of the patient's urine returned to normal when he did not eat beetroot. He was advised that beeturia is a harmless occurrence and that, even though beetroot colored his urine, he did not need to exclude the vegetable from his diet.

TIP for Allergy Advisor users: When entering "beetroot" in the search function of Allergy Advisor, the following information on beetroot can be obtained: background information on the vegetable (where it is grown, what it is used for including the uses of its red pigment in the food industry); the allergens that have been identified in beetroot; what allergy reactions have been previously reported, how common the allergy reactions are; what non-allergic reactions may occur; and that beetroot can contain the following constituents: betanin, nitrates, oxalate, phenolic acids and succinic acid to which adverse reactions can be experienced.

B. More information
The production of pink or red urine following beetroot ingestion is known as beeturia. This phenomenon is often misinterpreted as hematuria (blood in the urine) by the unsuspecting. However, it is in fact the red beetroot pigment that colors the urine. In some individuals the pigment passes intact along the gastrointestinal tract. A proportion is absorbed and excreted in the urine, and the remainder passes out in the stool.^1,2,3,4,5

How many experience beeturia? Beeturia occurs in about 10-14% of the human population. There is a variable frequency in the occurrence of beeturia in some individuals, while others consistently experience it after eating beetroot.1,2,3,4,5 It has also (incorrectly) been suggested that beeturia is linked with food allergies and malabsorption syndromes.1 Beeturia is most common in individuals with enhanced iron absorption: in 66-80% of patients with untreated iron-deficiency anemia, 45% of patients receiving treatment for pernicious anemia (augmented iron absoption occurs in this disease during Vitamin B12 treatment), and 33% in non-anemic patients with both malabsorption and biopsy-proven jejunal atrophy (the jejenum plays an important role in iron absorption).3,4,6,7 This suggests that beeturia is more likely to occur at a time of "iron hunger" perhaps via the pathway for iron absorption. Because beeturia can appear and disappear in individuals, at least some of the 14% incidence may be due to the fluctuating nature of iron absorption in normal individuals. 6,7 The complete mechanism has not been identified and the methods used in these studies have received critisism. In any case, a history of or the observation of beeturia in an infant or child should alert the physician to the presence of an associated iron deficiency anemia.2

Why might this occur?
It has been suggested that beeturia is controlled by a single autosomal gene, with 43% of the population being heterozygous for the gene.⁴ But this viewpoint has received criticism. It has been found that beeturia will always be present in any population study that is done, and during repeat investigations the results for any particular individual within a group may change. This is to be not expected for an event under genetic control.^1,7(There is room, however, for disagreement with this conclusion, as genetically determined enzyme deficiency is not necessarily absolute, but can occur in many degrees of severity.)

It is also suggested that beeturia is dose-related, but studies have contested this.⁴

Beetroot's red pigment, widely used in the food industry as a colorant, is betalain (also known as betalaine) consisting of betacyanines and betaxanthines. About 0.5-1% of extracted beet juice solids are betalains. In addition to the pigments, the root contains about 700-800mg oxalic acid and 5-6mg ascorbic acid per 100g beetroot.⁴

The pigment is a pH and redox indicator. It is structurally unstable at the extremes of pH, loosing its color in alkaline conditions and undergoing irreversible decomposition (to red or yellow) in acid solution. Studies have shown that betalain is decolorized by hydrochloric acid, ferric ions and colonic bacteria preparations, but not by pancreatic or mucosal enzymes. It has been suggested that the red color is stabilized by reducing agents, including oxalic acid and ascorbic acid, until it can reach the colon and be absorbed.^1,4

In non-beeturic individuals the pigment is decolorized by non-enzymic processes in the stomach and colon. The acid conditions of the stomach might also be expected to decolorize the red pigment, but it has been postulated that the oxalic acid and ascorbic acid stabilize the pigment throughout the passage through the stomach. Beeturia results from colonic absorption of betalain. Although it has been suggested that oxalic acid and ascorbic acid preserves the red color to the colon, it has now been shown that an intake of 1g ascorbic acid together with beetroot does not induce beeturia. The reason suggested for this was that ascorbic acid is absorbed from the jejenum and does not pass to the colon. (But it might still help in preserving the red color up to that point.) It is thus oxalic acid that preserves the red color all the way to the colon.⁴

It seems that the difference between a non-beeturic individual and a beeturic individual rests with oxalic acid in the colon. The more oxalic acid present in the colon, the more pigment available for absorption, which then determines if the urine will be colored. The concentration of oxalic acid will depend on the residue of the enteric oxalic acid not absorbed from the small intestine (which can vary between individuals). Another variable is the colonic bacterial metabolism. It has been hypothesizeded that beeturia can be influenced by the presence or absence of a bacterial decolorizing system. This theory was based on in vitro experiments and is difficult to prove or disprove. There are around 500 species of bacteria in the colon whose enzymes can be induced and have an influence on the pigments that are present in the colon. Urinary oxalic acid content probably has no influence on beeturic status, and little relationship with the colonic concentration.^1,4

Also, one could expect an association with beeturia and certain conditions, e.g., calcium oxalate kidney stones and short bowel syndrome where the level of oxalate intake is generally restricted.

Beeturia is thus affected by the quantity of pigment entering the systemic circulation, and this in turn is influenced by:

Beeturia is thus a function of an individual's physiological constitution and not a phenomenon under direct polymorphic genetic control as originally implied.¹

What factors can influence beeturia? The type of beetroot. Individuals who produce an intense coloration with one variety can produce urine with a virtually normal coloration with another. The pigment concentration of the "Detroit Rubidus" variety is twice than that of the "Firechief" variety, for example.1,7 The times of planting and harvesting. Additionally, concentrated beetroot extract is added to certain brands to enhance coloration. These factors, amongst others, can help in explaining the variation in results in the literature.1,7 Preparation. Boiled beetroot does not predictably lead to beeturia, whereas pickled beetroot does. The acid vinegar may alter the state of the oxalic acid.4 Intestinal function. Where there is reduced absorption from the small intestine, as in malabsorption, more oxalic acid would pass to the colon to protect the pigment and induce beeturia.1,4

More newsletters on other food idiosyncracies will follow in the next 6 months.

C. Comments by our editors

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D. References
1. Mitchell SC. Food idiosyncrasies: beetroot and asparagus. Drug Metab Dispos 2001;29:539-43.
2. Tunnessen WW, Smith C, Oski FA. Beeturia. A sign of iron deficiency. Am J Dis Child 1969 Apr;117(4):424-6.
3. Sotos JG. Beeturia and iron absorption. Lancet 1999 Sep 18;354(9183):1032.
4. Eastwood MA, Nyhlin H. Beeturia and colonic oxalic acid. QJM 1995 Oct;88(10):711-7.
5. Watts AR, Lennard MS, Mason SL, Tucker GT, Woods HF. Beeturia and the biological fate of beetroot pigments. Pharmacogenetics 1993 Dec;3(6):302-11.
6. Watson WC, Luke RG, Inall JA. Beeturia: its incidence and a clue to its mechanism. Br Med J 1963;2:971-2.
7. Charlton RW, Bothwell TH. Iron absorption. Ann Rev Med 1983;34:55-68.
8. Pearcy RM, Mitchell SC, Smith RL. Beetroot and red urine. Biochem Soc Trans 1992 Feb;20(1):22S.

E. CPD Questions (South Africa, Australia)

This CPD session is now closed. Please contact karen@allergyadvisor.com for more information.

PLEASE ANSWER ALL THE QUESTIONS
1. What percentage of the human population is affected by beeturia?
(a.) 5%
(b.) 10-14%
(c.) 43%
(d.) 95%

2. True or false: There is a variable frequency in the occurrence of beeturia in some individuals, while others consistently experience it after eating beetroot.
(a.) True
(b.) False

3. Which of the following has beeturia not been associated with?
(a.) Food allergies
(b.) Malabsorption syndromes
(c.) Iron-deficiency anemia
(d.) Hematuria

4. For which of the following statements are there sufficient scientific evidence?
(a.) Beeturia is controlled by a single autosomal gene
(b.) Beeturia is dose dependant
(c.) Beeturia is determined by the concentration of ascorbic acid present in the colon
(d.) Beeturia is determined by the concentration of oxalic acid present in the colon

5. Which of the following is betalain decolorized by in the human body?
(a.) Hydrochloric acid and ferric ions
(b.) Pancreatic enzymes and mucosal enzymes
(c.) Oxalic acid and ascorbic acid
(d.) Oxalic acid alone

6. Which of the following does not influence the concentration of oxalic acid in the colon?
(a.) The residue of oxalic acid not absorbed from the small intestine
(b.) The colonic bacterial metabolism
(c.) Urinary oxalic acid content
(d.) Amount of oxalic acid absorbed from the gut

7. True or false: Individuals who present with beeturia after ingestion of one variety can have no beeturia with another.
(a.) True
(b.) False

8. True or false: Boiled beetroot leads to beeturia, whereas pickled beetroot does not.
(a.) True
(b.) False

Answers

1. a [ ] b [X] c [ ] d [ ]		2. a [X] b [ ]		3. a [ ] b [ ] c [ ] d [X]
4. a [ ] b [ ] c [ ] d [X]		5. a [X] b [ ] c [ ] d [ ]		6. a [ ] b [ ] c [X] d [ ]
7. a [X] b [ ]		8. a [ ] b [X]

1. b. 10-14%
2. a. True
3. d. Hematuria
4. d. Beeturia is determined by the concentration of oxalic acid present in the colon
5. a. Hydrochloric acid and ferric ions
6. c. Urinary oxalic acid content
7. a. True
8. b. False

Index