Psychomicrobiology - Yeast infection and Psychiatric disorders

OCTOBER 2010 DELHI PSYCHIATRY JOURNAL Vol. 13 No. 2

Psychomicrobiology

Delhi Psychiatry Journal 2010; 13:(2) © Delhi Psychiatric Society

Yeast Infection and Psychiatric disorders

Malhotra S*, Nirmaljit Kaur*, Bhatia MS**, Kumar P*, Hans C*

*Department of Microbiology, Dr RML PGIMER and Hospital, New Delhi-110001.

** Department of Psychiatry, UCMS & GTB Hospital, Delhi-110095

Introduction

Millions of people suffer from depression

caused by multiple factors including certain

infections like candidiasis every year and the cause

in most cases is not known and this can be attributed

to the fact that in modern medicine and CNS, there

are very few knowns. It is well known that yeast

like Candida albicans can penetrate any area of the

body including CNS and henceforth there could be

a link between Candida infection and depression.

It has been observed that sign and symptoms of

yeast infection include skin rash, fatigue, headache,

irritability, intestinal pain, respiratory disorders,

urinary problems, vaginitis and depression1. Other

symptoms include digestive disorders hypoglycemia,

hyperactivity, memory loss, impotence,

learning difficulty, menstrual problems,

premenstrual tension and short attention. As evident

from the above list many symptoms are associated

with nervous system which plays a role in

psychiatric diseases. So we review this topic to

understand and highlight the correlation between

yeast infection and psychiatric disorders.

Terminology

Depression: is a universally understood

condition of sadness and despondency where patient

feels that life has lost its luster. People normally

recover from such gloomy spells and may carry on.

Some conditions of sadness may require lifestyle

changes such as resolving a rocky marriage,

dropping bad habits, or removing oppressive factors

from one’s life. Still other situations may require

the counsel of a good friend or priest or ministersomeone

one can trust and discuss his or her

troubles with. However sometimes people don’t

recover from life’s setbacks. Or they become

depressed over insignificant matters for no reason

at all. The feelings of sadness may simply slow them

down or can debilitate them to the point where they

weep continuously, cannot function in life or may

consider suicide. These are the situations where an

emergency psychiatric treatment is required2.

Causes of depression: When a person remains

depressed despite normal efforts to treat the

depression, a physical source of the depression

should be considered. This is particularly true in

the case of debilitating or suicidal depression2.

Physiological causes of depression are very

common, like endocrinal disorders in the form of

hypothyroidism.

Physical causes of depression include:

Nutritional deficiencies, lack of exercise, hypothyroidism,

hyperthyroidism, fibromyalgia, candida

(yeast infection), poor adrenal function, other

hormonal disorders including (cushing’s disease

(excessive pituitary hormone production, addison’s

disease (low adrenal function), high levels of

parathyroid hormone and low levels of pituitary

hormones), hypoglycemia, food Allergies, heavy

metals (such as mercury, lead, aluminium,

cadmium, and thallium), selenium toxicity,

premenstrual syndrome and sleep disturbances.

Infectious causes: AIDS, influenza, mononucleosis,

syphilis (late stage), tuberculosis, viral

hepatitis and viral pneumonia

Medical ailments/causes: Heart problems,

lung disease, diabetes, multiple sclerosis,

rheumatoid arthritis, chronic pain, chronic

inflammation, cancer, train tumors, head injury,

multiple sclerosis, parkinson’s disease, stroke,

temporal lobe epilepsy, systemic lupus

erythematosus and liver disease

Drugs related causes: Tranquilizers and

sedatives, antipsychotic drugs, amphetamines

(withdrawal from), antihistamines, beta blockers,

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high blood pressure medications, birth control pills,

anti inflammatory agents, corticosteroids (adrenal

hormone agents, cimetidine, cycloserine (an

antibiotic), indomethacin, reserpine, vinbiastine and

vincristine

Candidiasis – Common yeast infections called

candidiasis is caused by the yeast Candida albicans

which thrives in the large intestines of human body.

Yeast infections can manifest on skin, mouth or

systemic sites. It affects people of all ages and both

sexes3.

􀁺 Pre disposing factors – Moist environment

supports fungal growth and that’s the

reason most of fungi exist as saprophytes

in soil. Whenever human body’s immune

system gets compromised, fungal infections

manifest as opportunistic pathogen. The

prevalence of fungal infections has

increased since 1980 since the emergence

of HIV which causes AIDS where patient

is bound to get opportunistic fungal

infections when the CD4 count falls ,<500.

Of all the identified fungal mycosis, yeast

infection account for almost 70-80% of

infections4.

􀁺 Stages of Candidiasis – Today there are

millions of people in USA and other

countries who do not feel well and do not

seen to get a definitive answer as to why.

One potential reason which could be

hypothesized is of is the overgrowth of

Candida. While the human body has

abundant normal flora including Candida,

excess of Candida gives rise to any kind of

physical problem in the form of instant

fatigue, sugar craving, weight gain, lower

concentration, confusion, bloating, low

blood sugar, sensitivity to smells/alcohol,

migraine/headache and depression. The

course of Candidiasis has been divided into

following 5 stages3.

Stage One – During the first stage of Candida

infection, the mucosal lining or mucous membrane

become infected leading to allergic reactions along

with various types of infections such as

streptococcus throat, bronchiolitis, pneumonia,

tonsillitis, mononucleosis, sinusitis etc5.

Stage Two – This stage manifests in the form

of headache or migraine, joint pain, fatigue,

arthritis, nail infection, muscle soreness etc. due to

over production of certain metabolic chemicals by

Candida.

Stage Three – This is the stage during which

patient develops behavioral and psychiatric

problems. This includes decreased concentration,

mood swings, depression, forgetfulness and

confusion. At this stage, the patient feels out of

control. Patients may land up in severe depression

leading to thoughts of suicide, irrational fears, panic

attacks, phobias, epilepsy and uncontrolled

violence.

Stage Four – As Candida continues to grow

and destroy the body cells, organ system within the

body start reacting negatively and target towards a

shutdown e.g. when Candida infections affects GIT,

patient may not feel like eating and also the

absorption of nutrients from GIT also get

compromised. It is also hypothesized that it can

affect CVS and lead to hypertension, numbness of

extremities, bruising, and palpitations etc6. During

the fourth stage, endocrine system may also get

affected along with musculoskeletal system and

respiratory system.

Stage Five – In the fifth and final stage, the

person would land up with systemic spread of

Candida which can prove to be fatal7.

Possible Etiologies

Role of Tartaric acid in Autism: Innumerable

studies in past have implicated the role of abnormal

organic acid produced by GIT flora in causing

human diseases e.g. inborn errors of metabolism

like phenylketonuria, tyrosinemia, maple syrup

urine diseases etc. The same have been

hypothesized as playing a role in psychiatric

diseases like, autism, schizophrenia, Alzheimer’s

diseases and even fibromyalgia. Urine organic

testing in all these clinical conditions has shown

elevated excretions of acidic products8.

These metabolic end products associated with

Candida infection is tartaric acid. This compound

forms sludge in the wine brewing process and has

to be removed. Wine is sugar water fermented by

yeast saccharomyces cerevisiae to alcohol and other

yeast products. Humans do not produce this

chemical.

Effect of antifungal agents on Tartaric acid:

There are a lot of clinical cases where the

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psychiatric symptoms in patient have been

controlled by giving antifungal treatment to the

patient e.g. a two year old patient was being

evaluated for autism and his urine tested positive

for organic acids. The child had been treated several

times for ear infection with antibiotics and had

developed oral thrush. Child’s behavior was badly

affected and he became hyperactive with insomnia,

lost his speech and eye contact with parents. Since

child’s organic acids including tartaric acid was

elevated in urine, a differential diagnosis of yeast

infection was kept in mind and he was started on

topical Nystatin (oral thrush). The child’s behavior

improved within a week and elevated organic acids

decreased in urine although it took over 60 days

for the urine tartaric acid to return to normal range8.

After 68 days of treatment the child’s mother

started running out of Nystatin and began giving

only half doses. During that time the tartaric acid

starting increasing. When she got the Nystatin

prescription refilled and restored the full dose of

Nystatin, the tartaric acid decreased. Thus it was

proved that Nystatin causes a marked reduction in

the urine tartaric acid. The other significant finding

was that even after two months of Nystatin, the

biochemical abnormality can reappear within a

short time of stopping the antifungal drug. Even

after six months of antifungal treatment, there is

often a biochemical “rebound” and loss of

improvements after discontinuing antifungal

therapy. This rebound also occurs after other

antifungal drugs as well. Several explanations are

possible for this phenomenon. One reason could

be that because of one or more defects in the

immune system such as lgA deficiency lgG

deficiency, or severe combined immunodeficiency

disease (SCID) which are found in most children

with autism, the yeast, which are everywhere in our

environment including the food we eat, repopulate

the intestinal tract very rapidly and these yeast being

very resistant may not be completely eliminated

even after six months of antifungal therapy. Another

theory proposed is that the yeast can genetically

transform some of the human cells that line the

intestinal tract and thus some of the human cells

then contain yeast DNA due to transformation.

These genetically transformed human cells produce

both yeast and human products and are somewhat

sensitive to antifungal drugs but are not killed by

them and produce yeast products whenever

antifungal drugs are absent. Moreover some of the

yeast are embedded deep in recesses of the intestinal

tract or in the deeper layers of the mucosa that lines

the intestine where they are relatively safe from the

drug. Although their numbers are small, they readily

repopulate the intestine after antifungals are

stopped. The most logical explanation given from

immunology.8

In addition to the immune system taking

inventory of its own cells, it seems increasingly

likely that the immune system also takes an

inventory of bacteria and yeast cells present in the

intestinal tract soon after birth. This inventory is

performed by a group of cells called the CD5 +Bcells,

which are among the which are among the

very first immunological cells to appear in the

developing embryo and appear to play a role in

tolerance to intestinal microorganisms in postnatal

life. These cells may play a role in regulating the

secretion of lgA, the antibody class that is secreted

into the intestinal tract and which may select which

microorganisms are tolerated in the intestinal tract.

Furthermore, the eradication of normal flora

especially when antibiotics are administered

repetitively during infancy may cause the

CD5+cells to reject these normal organisms at a

later age. Any cells that are on this early inventory

may be awarded immune tolerance and will not be

attacked later on by the immune system. Either

antibiotic use in infancy or yeast infection of the

mother during pregnancy may result in later immune

tolerance to yeast.

Response of Children with Autism to

Antifungal Therapy: Improvements commonly

cited by parents of autistic children treated with

antifungal therapy include: decreased hyperactivity,

more eye contact, increased vocalization (more

words and more usage), better sleep patterns, better

concentration, increased imaginative play, reduced

stereotypical behaviors (such as spinning objects),

and better academic performance.

More than 1000 children with autism have been

treated with a wide variety of antifungal agents such

as Nystatin, Lamisil, Sporanox, Nizoral, Diflucan,

caprylic acid, grapefruit seed extract, and garlic

extract with good clinical response in perhaps 80-

90%7. A survey of parents of autistic children by

Rimland reports that antifungal therapy is ranked

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the most effective (by a wide margin) of all drug

therapies used for the reduction of autistic

symptoms9.

Molecular Basis of Tartaric Acid Toxicity in

autism: Patients with autism generally excrete

tartaric acid in urine and it has been observed that

many of these patients have accompanying

hypotonia8. Biopsy of the muscle of autistic patients

with hypotonia revealed normal structural features

except for an unexplained “granularity” by electron

microscopy. Electromyography, EEG’s, brain scans,

and nerve conduction velocities have been found

to be all normal. Literature indicates that tartaric

acid is a highly toxic substance. As little as 12 gm

can cause human fatality with death occurring from

12 hours to 9 days after ingestion. Gastrointestinal

symptoms can be marked (violent vomiting and

diarrhea, abdominal pain, thirst) followed by

cardiovascular collapse and/or acute renal failure.

This compound especially damages the muscles and

the kidney and may even cause fatal human

nephropathy (kidney damage).

A Korean study found that a patient with autism

had a value of 6000 mmol/mol creatinine, a value

that is about 600 times the median normal value.

Assuming that the yeast in the intestine of the child

were producing tartaric acid at a constant rate, this

child was exposed to 4.5 grams per day of tartaric

acid, (over one-third of the reported lethal dose of

tartaric acid!) The child’s was given antifungal

treatment for 6 weeks and his Creatinine value

returned to normal within few weeks8.

Mechanism of Tartaric acid toxicity: Tartaric

acid is an analog (a close chemical relative) of malic

acid (Figure 1). Malic acid is a key intermediate in

the Krebs cycle, a biochemical process used for the

extraction of most of the energy from our food.

Presumably tartaric acid is toxic because it inhibits

the biochemical production of the normal

compound, malic acid. Tartaric acid is a known

inhibitor of the Krebs cycle enzyme fumarase which

produces malic acid from fumaric acid.

Role of Malic acid supplements in

Fibromyalgia

Interestingly, it has been found that tartaric acid

and/or other yeast byproducts are also elevated in

urine samples of adults with the disorder

fibromyalgia, a debilitating disease associated with

muscle and joint pain, depress-ion, foggy thinking,

and chronic fatigue8.

A large percentage of patients with fibromyalgia

respond favorably to treatment with malic

acid which is present in health food supplements

such as Fibrocare and Supermalic. This is because

supplements of malic acid are able to overcome the

toxic effects of tartaric acid by supplying deficient

malic acid.

Treatment with the antifungal drug Nystatin

kills the yeast and values for tartaric acid steadily

diminish with antifungal treatment. Fifty percent

of patients with fibromyalgia often suffer from

hypoglycemia even though their diet may have

adequate or even excessive sugar8.

One of the reasons for the hypoglycemia may

be due to the inhibition of the Krebs cycle by tartaric

acid. The Krebs cycle is the main provider of raw

materials such as malic acid that can be converted

to blood sugar (Figure 2) by the process called

gluconeogenesis when the body uses up its glucose

supply.

Fig. 1 – Composition of Malic and Tartaric Acids Fig. 2 - The Krebs cycle demonstrates the conversions of raw

materials into Glucose, the main fuel for the brain.

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If sufficient malic acid cannot be produced, the

body cannot produce the sugar glucose, which is

the main fuel for the brain. The person with

hypoglycemia feels weak and their thinking is foggy

because there is insufficient fuel for their brain. Of

course, consumption of sugar may provide shortterm

relief but which also stimulates yeast

overgrowth and within a short time symptoms are

even worse.

Role of Arabinose in Autism, Alzheimer’s

Disease and Schizophrenia

Arabinose is a five carbon sugar with an

aldehyde function called an aldose, which is

frequently elevated in autism. In some children with

autism, arabinose concentrations may exceed 50

times the upper limit of normal.

The exact biochemical role of arabinose is

unknown, but a closely related yeast alcohol arabitol

has been used as a biochemical indicator of invasive

candidiasis. None of studies have found elevated

arabitol in any of the urine samples tested and

arabinose has not been found in the culture media

of multiple isolates of Candida albicans isolated

from stool samples of autistic children8.

It is assumed that arabitol produced by yeast

in the intestinal tract is absorbed into the portal

circulation and then converted to arabinose by the

liver. Hypoglycemia occurs in inborn errors of

fructose metabolism in which fructose inhibits

gluconeogenesis and it is possible that children with

autism might be deficient in one or more enzymes

involved in the metabolism of pentoses. Elevated

protein-bound arabinose has been found in the

serum glycoproteins of schizophrenics and in

children with conduct disorders and alteration of

protein function by arabinose is another mechanism

by which arabinose might effect biochemical

processes.

Women with vulvovaginitis due to Candida

have been found to have elevated arabinose in the

urine; restriction of dietary sugar brought about a

dramatic reduction in the incidence and severity of

the vulvovaginitis. Thus, one of the mechanisms of

action of antifungal drug therapy for autism might

be to reduce the concentration of an abnormal

carbohydrate produced by the yeast that can not be

tolerated by the child with defective pentose

metabolism. Arabinose tolerance tests should be

able to rapidly determine if such biochemical

defects are present in children with autism8.

Molecular basis of Pentosidines toxicity in

Autism and Alzheimer’s diseases: Protein

modification caused by pentosidine formation is

associated with crosslink formation), decreased

protein solubility, and increased protease resistance.

The characteristic pathological structures associated

with Alzheimer disease contain modifications

typical of pentosidine formation. Specifically,

antibodies against pentosidine immunocytochemically

label neurofibrillary tangles and senile

plaques in brain tissue from patients with Alzheimer

disease8.

In contrast, little or no staining with antipentosidine

antibodies is observed in apparently

healthy neurons of the same brain. The modification

of protein structure and function caused by

arabinose could account for the biochemical and

insolubility properties of the lesions of Alzheimer

disease through the formation of protein crosslinks.

Since the process of pentosidine formation is

an oxidative one, the use of antioxidants as well as

antifungal therapy appears to be a promising therapy

for Alzheimer’s disease. Glutathione has been

reported to inhibit pentosidine formation.

Supplementation with the vitamins biotin, pyridoxal

(B-6), and lipoic acid (whose function at protein

epsilon amino groups may be blocked by

pentosidines derived from arabinose) might also be

beneficial because of functional deficiencies due

to pentosidine formation8.

Not surprisingly, neurofibrillary tangles similar

to those found in the brains of Alzheimer’s victims

have also been reported in the brain of an autistic

person at autopsy. It has been reported that frequent

urinary tract infections and high amounts of

circulating immune complexes are associated with

more severe Alzheimer disease. The use of

antibiotics to treat urinary tract infections would

of course lead to yeast overgrowth of the

gastrointestinal tract.

Conclusion

Products of gastrointestinal microorganisms

including yeast that have been largely ignored in

the past appear to play major roles in human

metabolism, development, aging, and disease10.

Elevation of yeast metabolites such as tartaric

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acid and arabinose are found in many of the same

disorders and are even more common in autism,

SLE, Alzheimer’s disease, fibromyalgia, attention

deficit hyperactivity, and chronic fatigue syndrome.

The arabinose may interfere with gluconeogenesis

and also may through pentosidine formation

significantly alter protein structure, transport,

solubility, and enzymatic activity as well as

triggering autoimmune reactions to the modified

proteins.

The finding of pentosidine in the neurofibrillary

tangles of Alzheimer’s brains and its absence from

normal areas of the brain may indicate a direct role

of a yeast byproduct in accelerating the normal

aging process. Tartaric acid from yeast overgrowth

has a direct toxic effect on muscles and is an

inhibitor of a key Krebs cycle enzyme that supplies

raw materials for gluconeogenesis and offers an

explanation for many of the symptoms of

fibromyalgia.

Thus psychiatric disorders require not only the

antipsychotic treatment but also antifungal to treat

the organic cause behind such illness.

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http.www.yeast infection advisor.com.

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yeast.

9. Biamonte M. Does your child have a yeast

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www.holistic help.net/candida.html

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