. 2022 Jan 3;12(1):62. doi: 10.3390/life12010062

Table 1.

Citations of major vitamin C common cold trials.

Trial [Refs] ⁽¹⁾	Total No. of Episodes	Total Citations from 1997–2020 ⁽²⁾	Constituent of the Placebo	p for Testing Vitamin C Effect (2-t)
Karlowski (1975) [33]	249	109	Lactose	0.046
Lewis (1975) [34] ⁽³⁾		11
Ludvigsson (1977) [51] ⁽⁴⁾	1279	20	not stated ⁽⁴⁾	0.016
Pitt (1979) [52] ⁽⁵⁾	1219	31	citric acid	0.023
Anderson (1972) [53] ⁽⁶⁾	1170	7	citric acid	0.001
Total excluding the Karlowski trial	3668	41
Hemilä (1996) re-analysis [47] of the Karlowski (1975) trial		29

⁽¹⁾ All four trials were randomized, double-blind, and placebo-controlled. ⁽²⁾ Web of Science search 2021-11-5. Total number of citations is smaller than the sum for the 3 RCTs, because some citing papers cited 2 or 3 of the above vitamin C RCT reports. ⁽³⁾ The Lewis (1975) [34] is another report of the Karlowski (1975) [33] trial. It reports standard errors and other data not described in the primary JAMA report. ⁽⁴⁾ Ludvigsson trial [51]: Outcome: “Absence from school because of upper respiratory tract infection”: decrease of 14% in vitamin C group. “Every class was divided at random into two groups…In one of the groups the children received daily a fizzy tablet which contained 1000 mg vitamin C; in the other group the fizzy tablet looked and tasted the same but contained 10 mg [vitamin C] carried out totally double blind” (p. 91–92). ⁽⁵⁾ Pitt and Costrini trial [52]: Outcome: “Severity of colds”: decrease of 5.1% in vitamin C group. “… recruits were assigned randomly to either the vitamin C or placebo group from a list of consecutive numbers randomized in pairs…The vitamin C tablets each contained 500 mg of ascorbic acid in the anhydrous form, and the placebo tablets were formulated from citric acid and were indistinguishable in appearance and taste from the vitamin C tablets…Neither the recruits or drill instructors nor the physicians and corpsmen who treated the recruits were aware of which pill any individual recruit was taking” (p. 908). ⁽⁶⁾ Anderson trial [53]: Outcome: “Total number of days confined to house”: decrease of 30% in vitamin C group. “Each bottle of tablets was assigned a code number derived from a computer-generated list of consecutive numbers, randomized in pairs…Particular care was taken to ensure that the vitamin and placebo tablets were indistinguishable in appearance and taste. Pure ascorbic acid has a very strong and characteristic flavour which is difficult to imitate, and we therefore used a formulation containing 200 mg. of sodium ascorbate, 75 mg. of ascorbic acid and an artificial orange flavouring. The taste of this formulation was well matched by a placebo preparation containing 30 mg. of citric acid and the same orange flavouring and fillers. The effectiveness of the matching was established by asking 30 individuals to taste both tablets, and using pure ascorbic acid as reference, to judge which tablet contained the vitamin. Sixteen persons selected the placebo tablet and 14 the vitamin tablet. The effectiveness of the matching was verified at the end of the main study by the answers to the question ‘Do you think you have been on the vitamin or placebo tablet?’ Approximately half of the 818 subjects answered ‘Don’t know’, and the remainder were divided almost equally between those who guessed correctly and those who did not… After the bottles had been labelled the list of numbers was given for safe-keeping to a colleague who was not involved in the study…subjects were allocated to vitamin and placebo in a strictly double-blind randomized manner and the code was not broken until after all the data had been transferred to punch cards and initial tabulations carried out” (p. 504).