Vitamin C and the common cold

CORRESPONDENCE

Vitamin

C

and

the

common

cold

To

the

Editor:

The

review

of

my

book,

Vitamin

C

and

the

Common

Cold,

which

was

published

in

the

August

21

issue

ofthe

Journal

as

a

"Viewpoint",

contains

some

serious

misstatements

and

mis-

representations

which

I

wish

to

cor¬

rect.

The

statement

is

made

that

the

author

and

his

critics

seem

to

agree

on

one

central

point.at

the

moment

there

is

no

scientifically

valid

evi¬

dence

that

"Pauling's

proposed

pro¬

phylaxis"

will

work.

This

statement

is

wrong.

Some

of

the

scientifically

valid

evidence

is

dis¬

cussed

in

the

following

paragraphs,

essentially

as

it

was

in

my

book.

In

my

book

I

stated

that

the

well-

designed

investigations

that

have

been

carried

out

have

involved

the

use

of

rather

small

quantities

of

ascorbic

acid

(1000

milligrams

per

day

or

less),

and

that

no

large-scale

study

had

been

carried

out

with

ascorbic

acid

in

large

amounts.

The

statement

by

Beaton

and

Whalen

was

probably

based

on

their

misunderstanding

of

this

com¬

ment

by

me.

The

reviewers

also

say

that

the

doses

that

I

propose,

1

to

2

g.

per

day,

have

never

been

subjected

to

con¬

trolled

clinical

trials.

This

statement

is

false.

The

investigation

by

Dr.

G.

Ritzel,

a

physician

with

the

Medical

Service

of

the

public

schools

of

the

city

of

Basel,

Switzerland,

published

in

1961,

was

carried

out

with

1000

mg.

of

ascorbic

acid

per

day,

and

gave

results

with

high

statistical

signifi¬

cance.

Beaton

and

Whalen

make

an

as-

tounding

misrepresentation

of

the

carefully

controlled

double-blind

study

carried

out

by

Drs.

Cowan

Diehl,

and

Baker

ofthe

University

of

Minnesota.

These

physicians

carried

out

a

very

good

double-blind

study

with

nearly

400

subjects,

half

of

whom

received

ascorbic

acid

in

aver¬

age

amount

180

mg.

per

day,

and

the

other

half

a

placebo,

over

a

period

of

28

weeks.

Careful

records

were

kept

of

the

number

of

colds

and

the

ma¬

nifestations

of

illness.

The

observa¬

tions

showed

a

decrease

in

incidence

of

the

common

cold

by

14%

in

the

ascorbic-acid

subjects,

relative

to

the

placebo

subjects.

Moreover,

there

was

a

decrease

in

integrated

morbidi¬

ty,

as

measured

by

the

average

num¬

ber

of

days

lost

from

school

because

of

colds,

per

subject,

by

31%

in

the

ascorbic-acid

subjects,

as

compared

with

the

placebo

subjects.

Both

of

these

decreases

are

statistically

sig¬

nificant.

Cowan,

Diehl

and

Baker

state

that

statistical

analysis

of

the

data

reveals

that

a

difference

as

large

as

this

would

arise

only

three

or

four

times

in

a

hundred

through

chance

alone,

and

that

one

may

consider

this

as

probably

a

significant

difference,

and

vitamin

C

supplement

to

the

diet

may

therefore

be

judged

to

give

a

"slight"

advantage

in

reducing

the

number

of

colds

experienced,

al¬

though

one

might

question

the

practi¬

cal

importance

of

such

a

difference.

It

is

my

opinion,

as

stated

in

my

book,

that

a

decrease

in

incidence

by

14%

and

decrease

in

integrated

morbidity

(days

of

illness)

by

31%

is

more

than

a

"slight"

advantage,

and

that

it

does

indeed

have

practical

importance.

Beaton

and

Whalen

misrepresent

this

study

by

introducing

a

confusing

discussion

of

an

insigniflcant

matter.

Cowan,

Diehl

and

Baker

asked

their

subjects

to

make

an

estimate

of

the

number

of

colds

that

they

had

had

during

the

preceding

year,

and

the

averages

of

these

estimates

are

given

in

the

paper.

It

is

pure

nonsense

to

lay

any

weight

on

these

values

for

es¬

timated

number

of

colds

during

the

preceding

year,

based

upon

the

mem¬

ory

of

the

subjects.

Yet

Beaton

and

Whalen

have

chosen

to

introduce

in

their

review

a

table

comparing

these

unreliable

numbers

with

the

observed

numbers

of

colds

during

the

period

of

the

investigation,

and

have

minimized

the

discussion

ofthe

reliable

decrease

in

incidence

of

colds

during

the

period

ofthe

study.

Moreover,

Beaton

and

Whalen

mention

that

the

number

of

complica¬

tions

might

be

considered

a

measure

of

severity

and

that

this

was

reported

in

the

original

paper

to

be

somewhat

higher

in

the

experimental

group

than

in

the

control

group.

Cowan,

Diehl

and

Baker

say

"those

who

took

the

vitamin

C

had,

if

anything,

more

complications

such

as

bronchitis,

oti¬

tis,

and

sinusitis

than

did

those

in

the

control

group."

The

fact

is

that

the

number

of

complications

in

these

groups

is

so

small

that

the

difference

does

not

have

statistical

significance,

and

accordingly

cannot

be

used

as

an

argument

for

impeaching

the

statisti¬

cally

significant

results

of

the

careful

study

by

Cowan,

Diehl

and

Baker.

Before

1961

there

might

have

been

some

justification

for

saying

that

more

evidence

is

needed

before

the

conclusion

is

accepted

that

ascorbic

acid

has

greater

value

than

a

placebo

in

providing

protection

against

the

common

cold

for

subjects

who

receive

ascorbic

acid

regularly

over

a

period

of

time

beginning

before

the

colds

have

been

incurred,

and

who

are

ex¬

posed

to

cold

viruses

in

the

ordinary

way,

by

contact

with

other

people.

448

C.M.A.

JOURNAL/SEPTEMBER

4,

1971/VOL.

105

In

1961,

however,

the

careful

study

by

Ritzel

was

published

in

Helvetica

Medica

Acta.

This

study

involved

279

subjects,

of

whom

140

received

1000

mg.

of

ascorbic

acid

per

day and

139

received

an

identical

placebo.

The

study

was

a

double-blind

one,

with

neither

the

subjects

nor

the

physicians

knowing

which

subjects

received

as-

corbic

acid

and

which

received

the

placebo.

Only

after

the

conclusion

of

the

work

were

the

records

turned

over

to

a

completely

independent

team

of

professionals,

who

carried

out

the

statistical

analysis,

and

were

provided

with

the

identification

of

the

tablets.

Each

subject

was

examined

every

day

by

physicians,

and

the

number

of

subjective

symptoms

of

illness

report-

ed

were

noted,

and

verified

to

some

extent

by

objective

examination

(measurement

of

body

temperature,

inspection

of

the

respiratory

organs,

auscultation

of the

lungs,

and

so

on).

Persons

who

showed

cold

symptoms

on

the

first

day

were

excluded

from

the

investigation.

The

results

were

that

the

ascorbic-acid

subjects

had

45%

fewer

colds

than

the

placebo

subjects,

and

that

the

average

number

of

days

of

illness

per

subject

was

61%

less

for

the

ascorbic-acid

subjects

than

for

the

placebo

subjects,

and

the

integrated

number

of

symptoms

(re-

corded

daily)

was

64%

less.

Accord-

ingly

the

number

of

colds

was

found

by

Ritzel

to

be

45%

less,

and

the

integrated

morbidity

(total

amount

of

illness

per

subject)

was

found

to

be

61

to

64%

less.

Each

of

these

results

is

statistically

significant.

The

null

hy-

pothesis

that

ascorbic

acid

has

no

more

value

than

a

placebo

is

rejected

with high

statistical

significance,

at

the

level

P(one-tailed)

less

than

0.01.

This

investigation

was

very

well

planned

and

executed.

I

have

not

seen

any

significant

criticism

of

it

that

would

justify

rejection

of

the

observa-

tions.

My

conclusion

is

that

the

regular

ingestion

of

about

200mg.

of

ascorbic

acid

per

day

leads

to a

decrease

in

incidence

of

colds

by

about

15%,

and

a

regular

ingestion

of

1000

mg.

a

day

leads

to

the

decreased

incidence

of

colds

by

about

45%.

Moreover,

these

quantities

of

ascorbic

acid

ingested

are

indicated

by

the

reported

results

to

lead

to

a

decrease

in

total

illness

(integrated

morbidity)

by

about

30%

and

60%,

respectively.

No

double-blind

investigation

that

has

been

published

has

led

to

the

result

that

the

hypothesis

that

ascor-

bic

acid

has

the

foregoing

amount

of

protective

value,

relative

to

a

placebo,

is

to

be

rejected

with

statistical

sig-

nificance.

There

is

no

doubt

that

vitamin

C

is

far

less

toxic

and

has

far

fewer

side

effects

than

aspirin

and

other

com-

monly

used

cold

medicines.

As

men-

tioned

above,

there

is

evidence

show-

ing

with

high

statistical

significance

that

vitamin

C,

taken

in

proper

amounts,

has

the

effect

of

decreasing

the

incidence

and

severity

of

the

com-

mon

cold,

whereas

the

ordinary

cold

medicines

do

not

have

this

effect.

I

find

it

shocking

that

physicians

and

nutritionists

should

misrepresent

the

facts

and

should

refuse

to

recognize

the

value

of

this

important

food,

vita-

min

C,

in

improving

health.

Linus

Pauling

Stanford

University,

Stanford,

Calif.

94305

To

the

Editor:

In

response

to

Dr.

Pauling's

letter

we

would

disagree

that

we

have

mis-

represented

either

his

book

or

the

controversy

that

has

surrounded

its

publication.

In

our

view

we

have

clearly

identified

our

personal

re-

sponses

to

a

series

of

pertinent

ques-

tions.

We

would

encourage

the

reader

to

examine

the

book

and

the

many

reviews

that

have

been

published

be-

fore

reaching

his

own

conclusion.

While

we

have

no

wish

to

alter

any

part

of

our

statement,

we

would

again

emphasize

our

major

conclusion.

In

our

opinion,

Dr.

Pauling's

proposal

has

had

insufficient

field

testing

to

warrant

the

widespread

implementa-

tion

he

advocates.

The

solution,

as

we

suggest

in

our

article,

is

further

field

testing

with

full

clinical

supervision.

Until

such

testing

is

done,

the

con-

troversy

will

continue

or

the

proposal,

sound

or

unsound,

will

be

gradually

forgotten.

Perhaps

a

Canadian

clini-

cal

group

would

be

prepared

to

under-

take

a

study

designed

to

provide

defi-

nite

answers.

G.

W.

Beaton,

Ph.D.

and

S.

Whalen,

B.Sc.

Department

of

Nutrition,

School

of

Hygiene,

University

of

Toronto,

Toronto

5,

Ont.

Levodopa

and

amyotrophic

lateral

sclerosis

To

the

Editor:

In

a

recent

paper1

we

suggested

that

the use

of

high

doses

of

levodopa

might

be

useful

in

the

treatment

of

progressive

amyotrophic

lateral

scle-

rosis

(ALS).

This

statement

was

based

on

biochemical

observations

in

Darvon

Compound-65

Oesc,iption:

Darvon

is

a

unique

analgesic

discovered

and

synthesized

in

the

Lilly

Research

Laboratories.

Damon

Compound-OS

combines

the

analgesic

advantages

of

Darvon

with

the

annipyrenic

and

anti-inflammatory

bene-

fits

of

acenylsalicylic

acid

and

phenacenin.

When

inflam-

mation

is

present,

the

combination

redoces

discomfort

to

a

greater

extent

than

dues

either

analgesic

given

alone.

Each

Pulvole

contains:

65

mg.

propoxyphene

hydro-

chloride,

Lilly;

227

mg.

ASA..

162

mg.

phenacetin.

and

32.4

mg.

caffeine.

If

indicated,

Darvon

with

ASA.,

which

replaces

phenacetin

and

caffeine

with

additional

ASA..

may

be

used.

Indic.vtions:

Darvon

is

indicated

for

the

reduction

or

amelioration

of

mild

no

moderate

pain.

In

is

of

particular

value

for

pain

associated

with

re-current

or

chronic

dis-

ease.

When

propoxyphene

is

given

in

therapeutic

doses.

euphoria

is

non

observed,

tolerance

dues

not

occur,

and

physical

dependence

does

non

develop.

Damon

does

not

reduce

fever

or

diminish

inflammatory

reactions.

Conf,aindiceiions:

No

definite

contraindicanions

to

the

use

of

propoxyphene

have

been

reported.

Therapeutic

doses

have

produced

no

demonstrable

effects

on

respiro-

tion,

blood

pressure,

or

reflex

activity.

The

presence

of

acute

or

chronic

disease

has

not

pro-

duced

unusual

responses

during

therapy

with

propoxy-

phene.

Wa,nings:

Salicylates

should

be

used

with

caution

in

the

presence

of

gastric

ulcers

and

annicoagulanos.

The

pro-

longed

and

excossive

use

of

phenacesin-connaining

prod-

ucts

may

aggravate

renal

disease.

Side-Effects:

Moderate

constriction

of

the

pupils

has

been

observed

with

single

doses

of

100

and

200

mg.

Huge

doses

may

be

accompanied

by

dizziness,

sedation,

and

somnolence.

Occasionally,

a

skin

rash

or

a

gastro-innosninal

dis-

turbance

has

occurred.

If

such

symptoms

appear,

adminis-

tration

of

Darvon

Compound-OS

should

he

discontinued

until

the

cause

of

the

symptoms

can

be

determined.

In

some

instances,

gastric

irritation

accompanying

the

use

of

Darvon

Compound-65

or

Darvon

with

ASA.

may

be

directly

attributable

so

the

salicylane

in

the

preparation.

In

such

cases,

in

is

suggested

that

the

medication

be

taken

with

food

or

a

small

amount

of

milk.

P.ecauIions:

Patients

who

have

received

other

analgesic

drugs

for

long

periods

of

time

may

have

developed

physi-

cal

dependence

on

those

medications.

The

sudden

sub-

snisusion

of

propoxyphene

for

analgesics

so

which

patients

are

addicted

will

allow

withdrawal

symptoms

to

develop.

These

symptoms

are

nor

produced

by

propoxyphene

and

may

be

avoided

by

gradually

reducing

the

dose

of

the

old

medication

as

prupoxyphene

is

substituted.

This

process

may

require

from

several

days

no

one

week.

The

con-

comitant

administration

of

propoxyphene

and

orphena-

drine-connaining

compounds

is

non

recommended.

Overdosage:

Manifestations

of

accidental

or

intentional

overdusage

with

propoxyphene

are

similar

no

those

of

narcotic

overdosage

and

includo

convulsions

(more

com-

mon

than

ix

usually

noted

in

caste

of

narcotic

poisoning),

coma,

respiratory

depression,

and

circulatory

collapse.

When

combination

products

containing

salicylases

as

well

as

propoxyphene

have

been

ingested,

the

clinical

picture

may

be

complicated

by

salicylism.

Analeptic

drugs

(for

example,

caffeine

or

amphetamine)

should

nun

be

used

because

of

their

tendency

no

precipitate

fatal

convulsions.

Intravenously

administered

narcotic

antagonists

(nalorphine

and

lovallorphan)

are

the

drugs

of

choice

no

roverse

signs

of

intoxication.

Those

agents

should

be

given

repeatedly

until

the

patients

status

re-

mains

satisfacoory.

Gastric

lavage

also

may

be

helpful.

In

addition,

supportive

measures,

such

as

assisted

oxygena-

tion

and

intravenous

fluids,

should

be

used

as

indicated.

Dialysis

is

of

little

value

with

respect

no

propoxyphene

alone;

salicylanes

and

phenacetin

are

dialyzable.

Adminisueg

ion

andOosage.-

Taken

orally,

the

usual

dosage

of

Darvon

Compound-65

or

of

Damon

with

A.S.A.

is

1

Pulvule

3

or

4

times

daily.

ELI

LILLY

AND

COMPANY

(CANADA)

LIMITED

TORONTO,

ONTARIO

450

C.M.A.

JOURNAL/SEPTEMBER

4,

1971/VOL.

105